{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:23:47Z","timestamp":1783711427089,"version":"3.55.0"},"reference-count":204,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2019,3,16]],"date-time":"2019-03-16T00:00:00Z","timestamp":1552694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40\u201350 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr\u2122, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet\u00ae, MyoCet\u00ae, Marqibo\u00ae, Vyxeos\u00ae, and Onpattro\u2122, which are making positive impacts on patients\u2019 health. This review highlights the Canadian contribution to the development of these and other important liposomal technologies that have touched patients. In this review, we try to address the question of what drives innovation: Is it the individual, the teams, the funding, and\/or an entrepreneurial spirit that leads to success? From this perspective, it is possible to define how innovation will translate to meaningful commercial ventures and products with impact in the future. We begin with a brief history followed by descriptions of drug delivery technologies influenced by Canadian researchers. We will discuss recent advances in liposomal technologies, including the Metaplex technology from the author\u2019s lab. The latter exemplifies how a nanotechnology platform can be designed based on multidisciplinary groups with expertise in coordination chemistry, nanomedicines, disease, and business to create new therapeutics that can effect better outcomes in patient populations. We conclude that the team is central to the effort; arguing if the team is entrepreneurial and well positioned, the funds needed will be found, but likely not solely in Canada.<\/jats:p>","DOI":"10.3390\/pharmaceutics11030124","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T12:18:53Z","timestamp":1552911533000},"page":"124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["What Drives Innovation: The Canadian Touch on Liposomal Therapeutics"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-1248","authenticated-orcid":false,"given":"Ada W. Y.","family":"Leung","sequence":"first","affiliation":[{"name":"Cuprous Pharmaceuticals Inc., Vancouver, BC V6T 1Z4, Canada"},{"name":"Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada"},{"name":"Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Amador","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin Chuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urmi V.","family":"Mody","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel B.","family":"Bally","sequence":"additional","affiliation":[{"name":"Cuprous Pharmaceuticals Inc., Vancouver, BC V6T 1Z4, Canada"},{"name":"Experimental Therapeutics, BC Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada"},{"name":"Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada"},{"name":"Pharmaceutical Sciences, University of British Columbia, Vancouver, BC V6T 1Z3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,3,16]]},"reference":[{"key":"ref_1","first-page":"33","article-title":"Liposomes as Advanced Delivery Systems for Nutraceuticals","volume":"15","author":"Shade","year":"2016","journal-title":"Integr. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"D\u2019Souza, G.G.M. (2017). Liposomes Came First: The Early History of Liposomology. Liposomes: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-4939-6591-5"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/0304-4157(79)90012-1","article-title":"Lipid polymorphism and the functional roles of lipids in biological membranes","volume":"559","author":"Cullis","year":"1979","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Biomembr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1139\/o80-147","article-title":"Phospholipids and membrane transport","volume":"58","author":"Cullis","year":"1980","journal-title":"Can. J. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1080\/1061186X.2016.1221955","article-title":"Pieter Cullis\u2019 quest for a lipid-based, fusogenic delivery system for nucleic acid therapeutics: Success with siRNA so what about mRNA?","volume":"24","author":"Tam","year":"2016","journal-title":"J. Drug Target."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1016\/S0021-9258(18)62994-1","article-title":"Incorporation of lysozyme into liposomes. A model for structure-linked latency","volume":"245","author":"Sessa","year":"1970","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/0005-2728(70)90211-2","article-title":"Chlorophyll a-containing liposomes","volume":"223","author":"Trosper","year":"1970","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1042\/bj1290123","article-title":"Lysosomal localization of -fructofuranosidase-containing liposomes injected into rats","volume":"129","author":"Gregoriadis","year":"1972","journal-title":"Biochem. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/0014-5793(73)80394-1","article-title":"Drug entrapment in liposomes","volume":"36","author":"Gregoriadis","year":"1973","journal-title":"FEBS Lett."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/244170a0","article-title":"Enzyme-containing liposomes alleviate a model for storage disease","volume":"244","author":"Gregoriadis","year":"1973","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/0304-4165(83)90110-1","article-title":"Enhanced stability of \u03b2-galactosidase in parenchymal and nonparenchymal liver cells by conjugation with dextran","volume":"757","author":"Blomhoff","year":"1983","journal-title":"Biochim. Biophys. Acta (BBA) Gener. Subj."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/252252a0","article-title":"Liposomes as immunological adjuvants","volume":"252","author":"Allison","year":"1974","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0014-5793(74)80813-6","article-title":"Entrapment of proteins in liposomes prevents allergic reactions in pre-immunised mice","volume":"45","author":"Gregoriadis","year":"1974","journal-title":"FEBS Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2218","DOI":"10.1248\/cpb.23.2218","article-title":"Application of drug-containing liposomes to the duration of the intramuscular absorption of water-soluble drugs in rats","volume":"23","author":"Arakawa","year":"1975","journal-title":"Chem. Pharm. Bull."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1248\/cpb.23.3069","article-title":"Application of liposomes to the pharmaceutical modification of the distribution characteristics of drugs in the rat","volume":"23","author":"Tanaka","year":"1975","journal-title":"Chem. Pharm. Bull."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0006-291X(75)80433-5","article-title":"The effect of particle size and charge on the clearance rates of liposomes and liposome encapsulated drugs","volume":"63","author":"Juliano","year":"1975","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF00264195","article-title":"Liposomes as drug carrier system for cis-diamminedichloroplatinum (II). II. Antitumor activity in vivo, induction of drug resistance, nephrotoxicity and Pt distribution","volume":"21","author":"Steerenberg","year":"1988","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1023\/A:1018963006703","article-title":"Modulation of human ovarian tumor cell sensitivity to N-(phosphonacetyl)-l-aspartate (PALA) by liposome drug carriers","volume":"10","author":"Sharma","year":"1993","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/0006-291X(78)90613-7","article-title":"Long-living liposomes as potential drug carriers","volume":"82","author":"Desmukh","year":"1978","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1016\/0024-3205(80)90268-4","article-title":"Liposomes\u2014A selective drug delivery system for the topical route of administration. Lotion dosage form","volume":"26","author":"Mezei","year":"1980","journal-title":"Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1177\/00220345860650090501","article-title":"Liposomes as drug carriers for oral ulcers","volume":"65","author":"Harsanyi","year":"1986","journal-title":"J. Dent. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.3109\/02652049009040470","article-title":"Dermal drug delivery by liposome encapsulation: Clinical and electron microscopic studies","volume":"7","author":"Foldvari","year":"1990","journal-title":"J. Microencapsul."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.2174\/1389450115666140804224024","article-title":"Penetration Enhancer-Containing Vesicles: Does the Penetration Enhancer Structure Affect Topical Drug Delivery?","volume":"16","author":"Caddeo","year":"2015","journal-title":"Curr. Drug Targets"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/jphp.12385","article-title":"Exploring the co-loading of lidocaine chemical forms in surfactant\/phospholipid vesicles for improved skin delivery","volume":"67","author":"Caddeo","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/BF00130002","article-title":"Intravitreal liposome-encapsulated drugs: A preliminary human report","volume":"12","author":"Peyman","year":"1988","journal-title":"Int. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Bulbake, U., Doppalapudi, S., Kommineni, N., and Khan, W. (2017). Liposomal formulations in clinical use: An updated review. Pharmaceutics, 9.","DOI":"10.3390\/pharmaceutics9020012"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kalra, J., and Bally, M.B. (2013). Liposomes. Fundamentals of Pharmaceutical Nanoscience, Springer.","DOI":"10.1007\/978-1-4614-9164-4_3"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"501","DOI":"10.2217\/nnm.13.220","article-title":"Harnessing the potential of lipid-based nanomedicines for type-specific ovarian cancer treatments","volume":"9","author":"Leung","year":"2014","journal-title":"Nanomedicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0005-2736(79)90085-3","article-title":"Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes","volume":"557","author":"Olson","year":"1979","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/0005-2736(86)90302-0","article-title":"Vesicles of variable sizes produced by a rapid extrusion procedure","volume":"858","author":"Mayer","year":"1986","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_31","unstructured":"Cullis, P.R., Hope, M.J., and Bally, M.B. (1991). Extrusion Technique for Producing Unilamellar Vesicles. (US 5,008,050), U.S. Patent."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.chemphyslip.2013.10.011","article-title":"Novel methods for liposome preparation","volume":"177","author":"Patil","year":"2014","journal-title":"Chem. Phys. Lipids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1021\/ja0318030","article-title":"Controlled Vesicle Self-Assembly in Microfluidic Channels with Hydrodynamic Focusing","volume":"126","author":"Jahn","year":"2004","journal-title":"J. Am. Chem. Soc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1700375","DOI":"10.1002\/smtd.201700375","article-title":"State-of-the-Art Design and Rapid-Mixing Production Techniques of Lipid Nanoparticles for Nucleic Acid Delivery","volume":"2","author":"Evers","year":"2018","journal-title":"Small Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3633","DOI":"10.1021\/la204833h","article-title":"Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing","volume":"28","author":"Zhigaltsev","year":"2012","journal-title":"Langmuir"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e37","DOI":"10.1038\/mtna.2012.28","article-title":"Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA","volume":"1","author":"Belliveau","year":"2012","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ijpharm.2018.11.060","article-title":"Rapid and scale-independent microfluidic manufacture of liposomes entrapping protein incorporating in-line purification and at-line size monitoring","volume":"556","author":"Forbes","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_38","unstructured":"Bally, M.B., Zhang, Y.-P., Reimer, D.L., and Wheeler, J.J. (1998). Lipid-Nucleic Acid Particles Prepared via a hydrophobic Lipid-Nucleic Acid Complex Intermediate and Use for Gene Transfer. (US 5,705,385), U.S. Patent."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5756","DOI":"10.1021\/bi952847r","article-title":"Cationic lipid binding to DNA: Characterization of complex formation","volume":"35","author":"Wong","year":"1996","journal-title":"Biochemistry"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"12877","DOI":"10.1021\/bi00039a050","article-title":"Formation of Novel Hydrophobic Complexes between Cationic Lipids and Plasmid DNA","volume":"34","author":"Reimer","year":"1995","journal-title":"Biochemistry"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/0003-9861(85)90498-9","article-title":"Preservation of freeze-dried liposomes by trehalose","volume":"242","author":"Crowe","year":"1985","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_42","unstructured":"Janoff, A.S., Cullis, P.R., Bally, M.B., Fountain, M.W., Ginsberg, R.S., Hope, M.J., Madden, T.D., Schieren, H.P., and Jablonski, R.L. (1999). Methods of Dehydrating, Storing and Rehydrating Liposomes. (US 5,922,350), U.S. Patent."},{"key":"ref_43","unstructured":"Janoff, A.S., Cullis, P.R., Bally, M.B., Fountain, M.W., Ginsberg, R.S., Hope, M.J., Madden, T.D., Schieren, H.P., and Jablonski, R.L. (1989). Dehydrated Liposomes. (US 4,880,635), U.S. Patent."},{"key":"ref_44","unstructured":"Janoff, A.S., Cullis, P.R., Bally, M.B., Fountain, M.W., Ginsberg, R.S., Hope, M.J., Madden, T.D., Schieren, H.P., and Jablonski, R.L. (1996). Method of Dehydrating Liposomes Using Protective Sugars. (US 5,578,320), U.S. Patent."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0005-2736(85)90069-0","article-title":"Protection of large unilamellar vesicles by trehalose during dehydration: Retention of vesicle contents","volume":"817","author":"Madden","year":"1985","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.bbamem.2003.11.016","article-title":"pH gradient loading of anthracyclines into cholesterol-free liposomes: Enhancing drug loading rates through use of ethanol","volume":"1661","author":"Cox","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_47","unstructured":"Cabral-lilly, D., Mayer, L., Tardi, P., Watkins, D., and Zeng, Y. (2018). Method of Lyophilizing Liposomes. (14\/352,662), U.S. Patent."},{"key":"ref_48","first-page":"979","article-title":"Dehydration-Rehydration Vesicles: A Simple Method for High Yield Drug Entrapment in Liposomes","volume":"2","author":"Kirby","year":"1984","journal-title":"Bio\/Technology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1006\/abbi.1999.1525","article-title":"Modulation of Liposomal Membrane Fluidity by Flavonoids and Isoflavonoids","volume":"373","author":"Arora","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/0005-2736(85)90522-X","article-title":"Uptake of safranine and other lipophilic cations into model membrane systems in response to a membrane potential","volume":"812","author":"Bally","year":"1985","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.bbamem.2006.05.028","article-title":"Remote loading of doxorubicin into liposomes driven by a transmembrane phosphate gradient","volume":"1758","author":"Fritze","year":"2006","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/0005-2736(93)90218-O","article-title":"Accumulation of doxorubicin and other lipophilic amines into large unilamellar vesicles in response to transmembrane pH gradients","volume":"1149","author":"Harrigan","year":"1993","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/0009-3084(90)90131-A","article-title":"The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: A survey","volume":"53","author":"Madden","year":"1990","journal-title":"Chem. Phys. Lipids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/S0005-2736(98)00166-7","article-title":"Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients","volume":"1414","author":"Fenske","year":"1998","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.ijpharm.2005.04.029","article-title":"Encapsulation efficiency of water-soluble and insoluble drugs in liposomes prepared by the microencapsulation vesicle method","volume":"298","author":"Nii","year":"2005","journal-title":"Int. J. Pharm."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.ijpharm.2007.05.037","article-title":"Layersome: Development and optimization of stable liposomes as drug delivery system","volume":"344","author":"Ciobanu","year":"2007","journal-title":"Int. J. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.ijpharm.2017.11.028","article-title":"Hyaluronan-decorated liposomes as drug delivery systems for cutaneous administration","volume":"535","author":"Franze","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0005-2736(98)00168-0","article-title":"Loading of doxorubicin into liposomes by forming Mn2+-drug complexes","volume":"1414","author":"Cheung","year":"1998","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0005-2736(02)00507-2","article-title":"Formation of transition metal\u2013doxorubicin complexes inside liposomes","volume":"1565","author":"Abraham","year":"2002","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Wehbe, M., Anantha, M., Backstrom, I., Leung, A., Chen, K., Malhotra, A., Edwards, K., and Bally, M.B. (2016). Nanoscale Reaction Vessels Designed for Synthesis of Copper-Drug Complexes Suitable for Preclinical Development. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153416"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1080\/1061186X.2016.1186169","article-title":"PRCosomes: Pretty reactive complexes formed in liposomes","volume":"24","author":"Wehbe","year":"2016","journal-title":"J. Drug Target."},{"key":"ref_62","unstructured":"Hope, M.J., Madden, T.D., Cullis, P.R., Maier, M., Jayaraman, M., Rajeev, K.G., Akinc, A., and Manoharan, M. (2016). Methods and Compositions for Delivery of Nucleic Acids. (Application US 15\/152,216), U.S. Patent."},{"key":"ref_63","unstructured":"Hope, M.J., Semple, S.C., Chen, J., Madden, T.D., Cullis, P.R., Ciufolini, M.A., and Mui, B.L.S. (2015). Amino Lipids and Methods for the Delivery of Nucleic Acids. (US 9,139,554), U.S. Patent."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"8529","DOI":"10.1002\/anie.201203263","article-title":"Maximizing the Potency of siRNA Lipid Nanoparticles for Hepatic Gene Silencing In Vivo","volume":"51","author":"Jayaraman","year":"2012","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/0024-3205(77)90481-7","article-title":"Liposomes as drug carriers","volume":"20","author":"Fendler","year":"1977","journal-title":"Life Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1139\/y79-081","article-title":"Factors affecting the encapsulation of drugs within liposomes","volume":"57","author":"Stamp","year":"1979","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"975","DOI":"10.2147\/IJN.S68861","article-title":"Liposomes as nanomedical devices","volume":"10","author":"Bozzuto","year":"2015","journal-title":"Int. J. Nanomed."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0005-2736(76)90169-3","article-title":"Catecholamine uptake and concentration by liposomes maintaining pH gradients","volume":"455","author":"Nichols","year":"1976","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0304-4157(97)00006-3","article-title":"Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides and metal ions into large unilamellar vesicles","volume":"1331","author":"Cullis","year":"1997","journal-title":"Biochim. Biophys. Acta (BBA)-Rev. Biomembr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3109\/09687689409162233","article-title":"Ionophore-mediated loading of Ca2+ into large unilamellar vesicles in response to transmembrane pH gradients","volume":"11","author":"Wheeler","year":"1994","journal-title":"Mol. Membr. Biol."},{"key":"ref_71","first-page":"297","article-title":"Stealth liposomes: Review of the basic science, rationale, and clinical applications, existing and potential","volume":"1","author":"Immordino","year":"2006","journal-title":"Int. J. Nanomed."},{"key":"ref_72","unstructured":"Tardi, P., Johnstone, S., Webb, M., Bally, M., and Abraham, S. (2007). Liposome Loading with Metal Ions. (US 7,238,367), U.S. Patent."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jconrel.2006.05.019","article-title":"Copper\u2013topotecan complexation mediates drug accumulation into liposomes","volume":"114","author":"Taggar","year":"2006","journal-title":"J. Control. Release"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.jconrel.2004.02.017","article-title":"An evaluation of transmembrane ion gradient-mediated encapsulation of topotecan within liposomes","volume":"96","author":"Abraham","year":"2004","journal-title":"J. Control. Release"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1007\/s11095-006-9111-5","article-title":"Transition Metal-Mediated Liposomal Encapsulation of Irinotecan (CPT-11) Stabilizes the Drug in the Therapeutically Active Lactone Conformation","volume":"23","author":"Ramsay","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_76","unstructured":"DiGiulio, S. (2015). FDA approves onivyde combo regimen for advanced pancreatic cancer. Oncol. Times."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.leukres.2008.06.028","article-title":"In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy","volume":"33","author":"Tardi","year":"2009","journal-title":"Leukemia Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/02791072.1988.10472495","article-title":"The clinical use of disulfiram (Antabuse\u00ae): A review","volume":"20","author":"Banys","year":"1988","journal-title":"J. Psychoact. Drugs"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0039-9140(94)80105-3","article-title":"Spectrophotometric determination of copper(II), nickel(II) and cobalt(II) as complexes with sodium diethyldithiocarbamate in cationic micellar medium of hexadecyltrimethylammonium salts","volume":"41","author":"Marina","year":"1994","journal-title":"Talanta"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4129","DOI":"10.2147\/IJN.S137347","article-title":"Development and optimization of an injectable formulation of copper diethyldithiocarbamate, an active anticancer agent","volume":"12","author":"Wehbe","year":"2017","journal-title":"Int. J. Nanomed."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"10425","DOI":"10.1158\/0008-5472.CAN-06-2126","article-title":"Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and xenografts via inhibition of the proteasome activity","volume":"66","author":"Chen","year":"2006","journal-title":"Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1038\/bjc.2012.442","article-title":"Cytotoxic effect of disulfiram\/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells","volume":"107","author":"Liu","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1039\/C2MT00174H","article-title":"Copper complexes as therapeutic agents","volume":"4","author":"Duncan","year":"2012","journal-title":"Metallomics"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1021\/cr400135x","article-title":"Advances in copper complexes as anticancer agents","volume":"114","author":"Santini","year":"2013","journal-title":"Chem. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"185","DOI":"10.2174\/187152009787313837","article-title":"Copper complexes as anticancer agents","volume":"9","author":"Marzano","year":"2009","journal-title":"Anti-Cancer Agents Med. Chem."},{"key":"ref_86","first-page":"38","article-title":"Transition metal complexes as potential therapeutic agents","volume":"5","author":"Rafique","year":"2010","journal-title":"Biotechnol. Mol. Biol. Rev."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"10758","DOI":"10.1039\/C7DT01955F","article-title":"A Perspective\u2013can copper complexes be developed as a novel class of therapeutics?","volume":"46","author":"Wehbe","year":"2017","journal-title":"Dalton Trans."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0010-8545(02)00086-3","article-title":"Copper complexes of non-steroidal anti-inflammatory drugs: An opportunity yet to be realized","volume":"232","author":"Weder","year":"2002","journal-title":"Coord. Chem. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1007\/s10637-017-0488-2","article-title":"Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status","volume":"35","author":"Wehbe","year":"2017","journal-title":"Investig. New Drugs"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s13346-017-0455-7","article-title":"Development of a copper-clioquinol formulation suitable for intravenous use","volume":"8","author":"Wehbe","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"6334","DOI":"10.1002\/chem.201800289","article-title":"Transition Metal Ions Promote the Bioavailability of Hydrophobic Therapeutics: Cu and Zn Interactions with RNA Polymerase I Inhibitor CX5461","volume":"24","author":"Prosser","year":"2018","journal-title":"Chemistry"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jconrel.2018.07.025","article-title":"Copper-CX-5461: A novel liposomal formulation for a small molecule rRNA synthesis inhibitor","volume":"286","author":"Leung","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e955691","DOI":"10.4161\/21624011.2014.955691","article-title":"Consensus guidelines for the detection of immunogenic cell death","volume":"3","author":"Kepp","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev-immunol-032712-100008","article-title":"Immunogenic cell death in cancer therapy","volume":"31","author":"Kroemer","year":"2013","journal-title":"Ann. Rev. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nm1523","article-title":"Calreticulin exposure dictates the immunogenicity of cancer cell death","volume":"13","author":"Obeid","year":"2007","journal-title":"Nat. Med."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jinorgbio.2016.06.021","article-title":"Anticancer metal drugs and immunogenic cell death","volume":"165","author":"Terenzi","year":"2016","journal-title":"J. Inorg. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Mookerjee, A., Basu, J.M., Majumder, S., Chatterjee, S., Panda, G.S., Dutta, P., Pal, S., Mukherjee, P., Efferth, T., and Roy, S.J. (2006). A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo. BMC Cancer, 6.","DOI":"10.1186\/1471-2407-6-267"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/j.2042-7158.1976.tb04081.x","article-title":"The role of copper in preventing gastrointestinal damage by acidic anti-inflammatory drugs","volume":"28","author":"Boyle","year":"1976","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1007\/BF02786261","article-title":"Hypoglycemic effect of copper(II) acetate imidazole complexes","volume":"54","author":"Nahas","year":"1996","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4917","DOI":"10.1016\/j.bmc.2007.04.062","article-title":"Antidiabetic copper(II)-picolinate: Impact of the first transition metal in the metallopicolinate complexes","volume":"15","author":"Yasumatsu","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"e02280-17","DOI":"10.1128\/AAC.02280-17","article-title":"Copper Ions and Coordination Complexes as Novel Carbapenem Adjuvants","volume":"62","author":"Djoko","year":"2018","journal-title":"J. Antimicrob. Agents Chemother."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"3727","DOI":"10.1128\/AAC.02316-13","article-title":"Copper complexation screen reveals compounds with potent antibiotic properties against methicillin-resistant Staphylococcus aureus","volume":"58","author":"Haeili","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.1021\/cr040410w","article-title":"Copper homeostasis and neurodegenerative disorders (Alzheimer\u2019s, prion, and Parkinson\u2019s diseases and amyotrophic lateral sclerosis)","volume":"106","author":"Gaggelli","year":"2006","journal-title":"Chem. Rev."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1016\/j.ccr.2012.03.013","article-title":"Copper, zinc and iron in neurodegenerative diseases (Alzheimer\u2019s, Parkinson\u2019s and prion diseases)","volume":"256","author":"Kozlowski","year":"2012","journal-title":"Coord. Chem. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1002\/med.20174","article-title":"Copper in diseases and treatments, and copper-based anticancer strategies","volume":"30","author":"Tisato","year":"2010","journal-title":"Med. Res. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1021\/acs.molpharmaceut.7b00841","article-title":"The Pivotal Role of Copper in Neurodegeneration: A New Strategy for the Therapy of Neurodegenerative Disorders","volume":"15","author":"Giampietro","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"7143","DOI":"10.1021\/bi00079a011","article-title":"Mode of formation and structural features of DNA-cationic liposome complexes used for transfection","volume":"32","author":"Gershon","year":"1993","journal-title":"Biochemistry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1093\/nar\/5.4.1381","article-title":"Introduction of ribonucleic acids into cells by means of liposomes","volume":"5","author":"Dimitraidis","year":"1978","journal-title":"Nucleic Acids Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"3348","DOI":"10.1073\/pnas.76.7.3348","article-title":"Entrapment of a bacterial plasmid in phospholipid vesicles: Potential for gene transfer","volume":"76","author":"Fraley","year":"1979","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"10431","DOI":"10.1016\/S0021-9258(19)70482-7","article-title":"Introduction of liposome-encapsulated SV40 DNA into cells","volume":"255","author":"Fraley","year":"1980","journal-title":"J. Biol. Chem."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1080\/1061186021000066246","article-title":"A Lipid-based Delivery System for Antisense Oligonucleotides Derived from a Hydrophobic Complex","volume":"10","author":"Wong","year":"2002","journal-title":"J. Drug Target."},{"key":"ref_112","unstructured":"Wheeler, J., Bally, M.B., Zhang, Y.-P., Reimer, D.L., and Hope, M. (2005). Method of Preventing Aggregation of a Lipid: Nucleic Acid Complex. (US 6,858,224), U.S. Patent."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/sj.gt.3300821","article-title":"Stabilized plasmid-lipid particles: Construction and characterization","volume":"6","author":"Wheeler","year":"1999","journal-title":"Gene Ther."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nbt.1602","article-title":"Rational design of cationic lipids for siRNA delivery","volume":"28","author":"Semple","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Hu, Q., Shew, C.R., Bally, M.B., and Madden, T.D. (2001). Programmable fusogenic vesicles for intracellular delivery of antisense oligodeoxynucleotides: Enhanced cellular uptake and biological effects. Biochim. Biophys. Acta (BBA) Biomembr.","DOI":"10.1016\/S0005-2736(01)00294-2"},{"key":"ref_116","unstructured":"Holland, J.W., Madden, T.D., and Cullis, P.R. (2004). Liposome Having an Exchangeable Component. (US 6,673,364), U.S. Patent."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"498","DOI":"10.3390\/pharmaceutics5030498","article-title":"Advances in Lipid Nanoparticles for siRNA Delivery","volume":"5","author":"Tam","year":"2013","journal-title":"Pharmaceutics"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/B978-0-12-800148-6.00002-X","article-title":"Chapter Two\u2014Lipid Nanoparticles for Gene Delivery","volume":"Volume 88","author":"Huang","year":"2014","journal-title":"Advances in Genetics"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/j.jconrel.2005.06.014","article-title":"Cationic lipid saturation influences intracellular delivery of encapsulated nucleic acids","volume":"107","author":"Heyes","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/mt.2013.124","article-title":"Biodegradable lipids enabling rapidly eliminated lipid nanoparticles for systemic delivery of RNAi therapeutics","volume":"21","author":"Maier","year":"2013","journal-title":"Mol. Ther."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0165-6147(94)90314-X","article-title":"Long-circulating (sterically stabilized) liposomes for targeted drug delivery","volume":"15","author":"Allen","year":"1994","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0005-2736(89)90078-3","article-title":"Liposomes with prolonged circulation times: Factors affecting uptake by reticuloendothelial and other tissues","volume":"981","author":"Allen","year":"1989","journal-title":"Biochim. Biophys. Acta (BBA)-Biomembr."},{"key":"ref_123","first-page":"3320","article-title":"In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma","volume":"58","author":"Pilarski","year":"1998","journal-title":"Cancer Res."},{"key":"ref_124","unstructured":"Dos Santos, N. (2004). Characterization of Cholesterol-Free Liposomes for Use in Delivery of Anti-Cancer Drugs, University of British Columbia."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0006-291X(75)80180-X","article-title":"Homing of liposomes to target cells","volume":"65","author":"Gregoriadis","year":"1975","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/293226a0","article-title":"Cell-specific drug transfer from liposomes bearing monoclonal antibodies","volume":"293","author":"Leserman","year":"1981","journal-title":"Nature"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/0014-5793(89)80222-4","article-title":"Drug targeting in Leishmania donovani infections using tuftsin-bearing liposomes as drug vehicles","volume":"245","author":"Guru","year":"1989","journal-title":"FEBS Lett."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/0047-0740(79)90001-9","article-title":"Radionuclide-labelled liposomes\u2014A new lymph node imaging agent","volume":"6","author":"Osborne","year":"1979","journal-title":"Int. J. Nuclear Med. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1099\/00222615-14-2-213","article-title":"Localisation of experimental staphylococcal abscesses by 99MTC-technetium-labelled liposomes","volume":"14","author":"Morgan","year":"1981","journal-title":"J. Med. Microbiol."},{"key":"ref_130","first-page":"6387","article-title":"A New Concept for Macromolecular Therapeutics in Cancer Chemotherapy: Mechanism of Tumoritropic Accumulation of Proteins and the Antitumor Agent Smancs","volume":"46","author":"Matsumura","year":"1986","journal-title":"Cancer Res."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1126\/science.7423203","article-title":"Antibody targeting of liposomes: Cell specificity obtained by conjugation of F(ab\u2019)2 to vesicle surface","volume":"210","author":"Heath","year":"1980","journal-title":"Science"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"4229","DOI":"10.1021\/bi00517a043","article-title":"Immunospecific targeting of liposomes to cells: A novel and efficient method for covalent attachment of Fab\u2019 fragments via disulfide bonds","volume":"20","author":"Martin","year":"1981","journal-title":"Biochemistry"},{"key":"ref_133","first-page":"4817","article-title":"Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro","volume":"52","author":"Ahmad","year":"1992","journal-title":"Cancer Res"},{"key":"ref_134","first-page":"1172","article-title":"Anti-HER2 immunoliposomes: Enhanced efficacy attributable to targeted delivery","volume":"8","author":"Park","year":"2002","journal-title":"Clin Cancer Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1158\/1078-0432.CCR-08-2392","article-title":"Tumor-targeted nanomedicines: enhanced antitumor efficacy in vivo of doxorubicin-loaded, long-circulating liposomes modified with cancer-specific monoclonal antibody","volume":"15","author":"ElBayoumi","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"6732","DOI":"10.1158\/0008-5472.CAN-05-4199","article-title":"Antibody Targeting of Long-Circulating Lipidic Nanoparticles Does Not Increase Tumor Localization but Does Increase Internalization in Animal Models","volume":"66","author":"Kirpotin","year":"2006","journal-title":"Cancer Res."},{"key":"ref_137","first-page":"7190","article-title":"Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs","volume":"62","author":"Sapra","year":"2002","journal-title":"Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijpharm.2008.07.012","article-title":"Peptide ligand-mediated liposome distribution and targeting to EGFR expressing tumor in vivo","volume":"363","author":"Song","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.addr.2012.09.037","article-title":"Liposomal drug delivery systems: From concept to clinical applications","volume":"65","author":"Allen","year":"2013","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"10958","DOI":"10.1158\/0008-5472.CAN-07-2233","article-title":"Peptide-Mediated Targeting to Tumor Blood Vessels of Lung Cancer for Drug Delivery","volume":"67","author":"Lee","year":"2007","journal-title":"Cancer Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jconrel.2009.06.024","article-title":"A synthetic peptide mediated active targeting of cisplatin liposomes to Tie2 expressing cells","volume":"139","author":"Mai","year":"2009","journal-title":"J. Control. Release"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/sj.bjc.6604483","article-title":"Tumour-targeted nanomedicines: Principles and practice","volume":"99","author":"Lammers","year":"2008","journal-title":"Br. J. Cancer"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2013.11.009","article-title":"Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology","volume":"66","author":"Bertrand","year":"2014","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.plipres.2004.12.001","article-title":"Advanced strategies in liposomal cancer therapy: Problems and prospects of active and tumor specific drug release","volume":"44","author":"Andresen","year":"2005","journal-title":"Prog. Lipid Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/0014-5793(87)80506-9","article-title":"Large Unilamellar Liposomes with Low Uptake into the Reticuloendothelial System","volume":"223","author":"Allen","year":"1987","journal-title":"FEBS Lett."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/0925-4439(92)90010-K","article-title":"Enhanced Localization of Liposomes with Prolonged Blood-Circulation Time in Infected Lung-Tissue","volume":"1138","author":"Bakkerwoudenberg","year":"1992","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Parambath, A. (2018). 1\u2014PEGylated \u201cstealth\u201d nanoparticles and liposomes. Engineering of Biomaterials for Drug Delivery Systems, Woodhead Publishing.","DOI":"10.1016\/B978-0-08-101750-0.00001-5"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0005-2736(90)90440-Y","article-title":"Liposomes for the sustained drug release in vivo","volume":"1029","author":"Blume","year":"1990","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/0005-2736(95)00218-9","article-title":"Preparation and characterization of conjugates of (modified) human serum albumin and liposomes: Drug carriers with an intrinsic anti-HIV activity","volume":"1278","author":"Kamps","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_150","first-page":"59","article-title":"STERICALLY STABILIZED (\u201cSTEALTH\u201d)","volume":"3","author":"Allen","year":"1992","journal-title":"Liposome Technol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/08982100500364081","article-title":"6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization","volume":"15","author":"Agrawal","year":"2005","journal-title":"J. Liposome Res."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"341","DOI":"10.2174\/156720105774370294","article-title":"The Formulation of Lipid-Based Nanotechnologies for the Delivery of Fixed Dose Anticancer Drug Combinations","volume":"2","author":"Ramsay","year":"2005","journal-title":"Curr. Drug Deliv."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1158\/1535-7163.MCT-06-0118","article-title":"Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice","volume":"5","author":"Mayer","year":"2006","journal-title":"Mol. Cancer Ther."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1124\/mi.7.4.8","article-title":"Optimizing combination chemotherapy by controlling drug ratios","volume":"7","author":"Mayer","year":"2007","journal-title":"Mol. Int."},{"key":"ref_155","unstructured":"Janoff, A., Mayer, L., Redman, J., and Swenson, C. (2010). Fixed Ratio Drug Combination Treatments for Solid Tumors. (US 7,842,676), U.S. Patent."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1586\/14760584.7.8.1141","article-title":"Epaxal\u00ae: A virosomal vaccine to prevent hepatitis A infection","volume":"7","author":"Bovier","year":"2008","journal-title":"Expert Rev. Vaccin."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1016\/S0264-410X(03)00509-7","article-title":"Antibody titres after primary and booster vaccination of infants and young children with a virosomal hepatitis A vaccine (Epaxal\u00ae)","volume":"21","author":"Usonis","year":"2003","journal-title":"Vaccine"},{"key":"ref_158","first-page":"4730","article-title":"Enhancement of adriamycin delivery to liver metastatic cells with increased tumoricidal effect using liposomes as drug carriers","volume":"43","author":"Gabizon","year":"1983","journal-title":"Cancer Res."},{"key":"ref_159","unstructured":"Gabizon, A., and Barenholz, Y. (1988). Adriamycin-Containing Liposomes in Cancer Chemotherapy, Wiley."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0936-6555(05)80269-9","article-title":"Liposomal doxorubicin (Doxil): An effective new treatment for Kaposi\u2019s sarcoma in AIDS","volume":"6","author":"James","year":"1994","journal-title":"Clin. Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1128\/AAC.35.4.615","article-title":"Amphotericin B lipid complex therapy of experimental fungal infections in mice","volume":"35","author":"Clark","year":"1991","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3109\/08982109309150730","article-title":"Amphotericin B lipid complex (ABLC\u2122): A molecular rationale for the attenuation of amphotericin B related toxicities","volume":"3","author":"Janoff","year":"1993","journal-title":"J. Liposome Res."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1128\/AAC.41.10.2201","article-title":"Pharmacokinetic profile of ABELCET (amphotericin B lipid complex injection): Combined experience from phase I and phase II studies","volume":"41","author":"Adedoyin","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1200\/JCO.1996.14.8.2353","article-title":"Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi\u2019s sarcoma","volume":"14","author":"Gill","year":"1996","journal-title":"J. Clin. Oncol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"481","DOI":"10.3109\/08982109409037058","article-title":"Daunoxome\u00ae Treatment of Solid Tumors: Preclinical and Clinical Investigations","volume":"4","author":"Forssen","year":"1994","journal-title":"J. Liposome Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/sj.bmt.1701630","article-title":"Treatment of invasive fungal infections with amphotericin B colloidal dispersion in bone marrow transplant recipients","volume":"23","author":"Noskin","year":"1999","journal-title":"Bone Marrow Transplant."},{"key":"ref_167","first-page":"S3","article-title":"AmBisome targeting to fungal infections","volume":"14","year":"1994","journal-title":"Bone Marrow Transplant."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1093\/jac\/49.suppl_1.21","article-title":"Ambisome: Lipsomal formulation, structure, mechanism of action and pre-clinical experience","volume":"49","author":"Proffitt","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1093\/jac\/28.suppl_B.49","article-title":"Pharmacology and toxicology of a liposomal formulation of amphotericin B (AmBisome) in rodents","volume":"28","author":"Proffitt","year":"1991","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"4381","DOI":"10.1016\/j.vaccine.2009.05.029","article-title":"Eleven years of Inflexal\u00ae V\u2014A virosomal adjuvanted influenza vaccine","volume":"27","author":"Herzog","year":"2009","journal-title":"Vaccine"},{"key":"ref_171","first-page":"3394","article-title":"A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors","volume":"5","author":"Glantz","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1345\/aph.19347","article-title":"Clinical pharmacology of encapsulated sustained-release cytarabine","volume":"34","author":"Murry","year":"2000","journal-title":"Ann. Pharmacother."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/BF00273522","article-title":"Analysis of the effect of liposome encapsulation on the vesicant properties, acute and cardiac toxicities, and antitumor efficacy of doxorubicin","volume":"23","author":"Balazsovits","year":"1989","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0960-9776(01)80001-1","article-title":"Liposome technology and the development of Myocet\u2122(liposomal doxorubicin citrate)","volume":"10","author":"Swenson","year":"2001","journal-title":"Breast"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.2165\/00003495-200363220-00016","article-title":"Verteporfin","volume":"63","author":"Keam","year":"2003","journal-title":"Drugs"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/j.1600-0420.2004.00368.x","article-title":"Encouraging results of photodynamic therapy with Visudyne in a clinical patient material of age-related macular degeneration","volume":"82","author":"Frennesson","year":"2004","journal-title":"Acta Ophthalmol. Scand."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/BF00686214","article-title":"Extended-release formulation of morphine for subcutaneous administration","volume":"33","author":"Kim","year":"1993","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_178","first-page":"677","article-title":"L-MTP-PE and zoledronic acid combination in osteosarcoma: Preclinical evidence of positive therapeutic combination for clinical transfer","volume":"6","author":"Biteau","year":"2016","journal-title":"Am. J. Cancer Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"962101","DOI":"10.1155\/2012\/962101","article-title":"The safety of EXPAREL\u00ae(bupivacaine liposome injectable suspension) administered by peripheral nerve block in rabbits and dogs","volume":"2012","author":"Richard","year":"2012","journal-title":"J. Drug Deliv."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0163-7827(02)00004-8","article-title":"A lipid based depot (DepoFoam\u00ae technology) for sustained release drug delivery","volume":"41","author":"Mantripragada","year":"2002","journal-title":"Prog. Lipid Res."},{"key":"ref_181","first-page":"2830","article-title":"Liposomal vincristine which exhibits increased drug retention and increased circulation longevity cures mice bearing P388 tumors","volume":"54","author":"Boman","year":"1994","journal-title":"Cancer Res."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s002800050846","article-title":"Preclinical pharmacology, toxicology and efficacy of sphingomyelin\/cholesterol liposomal vincristine for therapeutic treatment of cancer","volume":"42","author":"Webb","year":"1998","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1158\/0008-5472.CAN-14-0572","article-title":"Preclinical activity of nanoliposomal irinotecan is governed by tumor deposition and intratumor prodrug conversion","volume":"74","author":"Kalra","year":"2014","journal-title":"Cancer Res."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1016\/j.leukres.2010.01.015","article-title":"Leukemia-selective uptake and cytotoxicity of CPX-351, a synergistic fixed-ratio cytarabine: Daunorubicin formulation, in bone marrow xenografts","volume":"34","author":"Lim","year":"2010","journal-title":"Leuk. Res."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1002\/jps.21620","article-title":"Pharmacokinetics of CPX-351 (cytarabine\/daunorubicin HCl) liposome injection in the mouse","volume":"98","author":"Bayne","year":"2009","journal-title":"J. Pharm. Sci."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"6122","DOI":"10.1073\/pnas.85.16.6122","article-title":"Unusual lipid structures selectively reduce the toxicity of amphotericin B","volume":"85","author":"Janoff","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ijpharm.2009.01.003","article-title":"Development and characterization of oral lipid-based Amphotericin B formulations with enhanced drug solubility, stability and antifungal activity in rats infected with Aspergillus fumigatus or Candida albicans","volume":"372","author":"Wasan","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"903","DOI":"10.2165\/00002018-200124120-00004","article-title":"A comparison of liposomal formulations of doxorubicin with drug administered in free form: Changing toxicity profiles","volume":"24","author":"Waterhouse","year":"2001","journal-title":"Drug Saf."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0076-6879(05)91004-5","article-title":"The liposomal formulation of doxorubicin","volume":"Volume 391","author":"Abraham","year":"2005","journal-title":"Methods in Enzymology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.bbamem.2004.03.006","article-title":"Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer","volume":"1663","author":"Charrois","year":"2004","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0005-2736(90)90018-J","article-title":"Liposomes with entrapped doxorubicin exhibit extended blood residence times","volume":"1023","author":"Bally","year":"1990","journal-title":"Biochim. Biophys. Acta (BBA) Biomembr."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.breast.2009.05.004","article-title":"Improving the therapeutic index of anthracycline chemotherapy: Focus on liposomal doxorubicin (Myocet\u2122)","volume":"18","author":"Leonard","year":"2009","journal-title":"Breast"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1023\/A:1020186505848","article-title":"Controlling the Physical Behavior and Biological Performance of Liposome Formulations Through Use of Surface Grafted Poly(ethylene Glycol)","volume":"22","author":"Allen","year":"2002","journal-title":"Biosci. Rep."},{"key":"ref_194","first-page":"1319","article-title":"Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: The lack of beneficial effects by coating liposomes with poly (ethylene glycol)","volume":"280","author":"Parr","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0005-2736(86)90105-7","article-title":"Uptake of adriamycin into large unilamellar vesicles in response to a pH gradient","volume":"857","author":"Mayer","year":"1986","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_196","first-page":"13","article-title":"Drug release characteristics of lipid based benzoporphyrin derivative","volume":"6","author":"Chowdhary","year":"2003","journal-title":"J. Pharm. Pharm. Sci."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0039-6257(00)00158-2","article-title":"Mechanisms of Action of Photodynamic Therapy with Verteporfin for the Treatment of Age-Related Macular Degeneration","volume":"45","author":"Hasan","year":"2000","journal-title":"Surv. Ophthalmol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1002\/jps.20332","article-title":"Optimization and Characterization of a Sphingomyelin\/Cholesterol Liposome Formulation of Vinorelbine with Promising Antitumor Activity","volume":"94","author":"Semple","year":"2005","journal-title":"J. Pharm. Sci."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1038\/bjc.1995.430","article-title":"Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models","volume":"72","author":"Webb","year":"1995","journal-title":"Br. J. Cancer"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.ijpharm.2010.02.014","article-title":"Biophysical characterization of a liposomal formulation of cytarabine and daunorubicin","volume":"391","author":"Dicko","year":"2010","journal-title":"Int. J. Pharm."},{"key":"ref_201","doi-asserted-by":"crossref","unstructured":"Tardi, P.G., Dos Santos, N., Harasym, T.O., Johnstone, S.A., Zisman, N., Tsang, A.W., Bermudes, D.G., and Mayer, L.D. (2009). Drug ratio\u2013dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo. Mol. Cancer Ther.","DOI":"10.1158\/1535-7163.MCT-09-0243"},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.2217\/fon-2017-0607","article-title":"Improving combination cancer therapy: The CombiPlex\u00ae development platform","volume":"14","author":"Tolcher","year":"2018","journal-title":"Future Oncol."},{"key":"ref_203","first-page":"329","article-title":"Synergistic antitumor activity observed for a fixed ratio liposome formulation of Cytarabine (Cyt):Daunorubicin (Daun) against preclinical leukemia models","volume":"65","author":"Johnstone","year":"2005","journal-title":"Cancer Res."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s40265-018-0983-6","article-title":"Patisiran: First Global Approval","volume":"78","author":"Hoy","year":"2018","journal-title":"Drugs"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/3\/124\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:38:19Z","timestamp":1760186299000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/11\/3\/124"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,16]]},"references-count":204,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2019,3]]}},"alternative-id":["pharmaceutics11030124"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics11030124","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,16]]}}}