{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T18:03:11Z","timestamp":1762624991234,"version":"build-2065373602"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2014Brasil (CAPES)","award":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"],"award-info":[{"award-number":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"]}]},{"name":"national funds from FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia, I.P.","award":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"],"award-info":[{"award-number":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"],"award-info":[{"award-number":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"],"award-info":[{"award-number":["001","UIDP\/04378\/2020","UIDB\/04378\/2020","LA\/P\/0140\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Traditional medicine uses resin oils extracted from plants of the genus Copaifera for several purposes. Resin oils are being studied to understand and profile their pharmacological properties. The aim of this work was to prepare and to characterize conventional and pegylated liposomes incorporating resin oils or the hexanic extract obtained from Copaifera sabulicola (copaiba) leaves. The cytotoxic effect of these products was also investigated. Conventional and stealth liposomes with copaiba extract showed similar average diameters (around 126 nm), encapsulation efficiencies greater than 75% and were stable for 90 days. A cytotoxicity test was performed on murine glioma cells and the developed liposomes presented antiproliferative action against these cancer cells at the average concentration of 30 \u03bcg\/mL. Phytochemicals encapsulated in PEGylated liposomes induced greater reduction in the viability of tumor cells. In addition, bioassay-s measured the cytotoxicity of copaiba resin oil (Copaifera sabulicola) in liposomes (conventional and PEGylated), which was also checked against pheochromocytoma PC12 cells. Its safety was verified in normal rat astrocytes. The results indicate that liposomes encapsulating copaiba oil showed cytotoxic activity against the studied tumor strains in a dose-dependent fashion, demonstrating their potential applications as a chemotherapeutic bioactive formulation.<\/jats:p>","DOI":"10.3390\/pharmaceutics15020671","type":"journal-article","created":{"date-parts":[[2023,2,17]],"date-time":"2023-02-17T02:27:24Z","timestamp":1676600844000},"page":"671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Conventional and PEGylated Liposomes as Vehicles of Copaifera sabulicola"],"prefix":"10.3390","volume":"15","author":[{"given":"Ian M. R.","family":"Blanco","sequence":"first","affiliation":[{"name":"Industrial Engineering Program, Polytechnic School, Federal University of Bahia, Salvador 40210-630, Bahia, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3798-5512","authenticated-orcid":false,"given":"Raquel de Melo","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Campus of Cartuja s\/n, 18071 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-8146","authenticated-orcid":false,"given":"Julita M. P.","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Science and Technology, State University of Southwestern Bahia, Salvador 45083-900, Bahia, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8617-3724","authenticated-orcid":false,"given":"Silvio A. B. Vieira","family":"de Melo","sequence":"additional","affiliation":[{"name":"Industrial Engineering Program, Polytechnic School, Federal University of Bahia, Salvador 40210-630, Bahia, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3321-0392","authenticated-orcid":false,"given":"Ramon dos Santos","family":"El-Bach\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, UFBA, Salvador 40170-110, Bahia, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2219-3566","authenticated-orcid":false,"given":"C\u00e9sar","family":"Viseras","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Granada, Campus of Cartuja s\/n, 18071 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6527-6612","authenticated-orcid":false,"given":"Patricia","family":"Severino","sequence":"additional","affiliation":[{"name":"Biotechnological Postgraduate Program, Tiradentes University, Aracaju 49010-390, Sergipe, Brazil"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2571-108X","authenticated-orcid":false,"given":"Elena","family":"Sanchez-Lopez","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08007 Barcelona, Spain"},{"name":"Unit of Synthesis and Biomedical Applications of Peptides, IQAC-CSIC, 08034 Barcelona, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9737-6017","authenticated-orcid":false,"given":"Eliana B.","family":"Souto","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Elaine","family":"Cabral-Albuquerque","sequence":"additional","affiliation":[{"name":"Industrial Engineering Program, Polytechnic School, Federal University of Bahia, Salvador 40210-630, Bahia, Brazil"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1590\/S0074-02762008000500006","article-title":"Brazilian flora extracts as source of novel antileishmanial and antifungal compounds","volume":"103","author":"Tempone","year":"2008","journal-title":"Mem\u00f3rias Inst. Oswaldo Cruz"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.sjbs.2015.10.009","article-title":"Phenolic composition and antiparasitic activity of plants from the Brazilian Northeast \u201cCerrado\u201d","volume":"23","author":"Gomez","year":"2016","journal-title":"Saudi J. Biol. Sci."},{"doi-asserted-by":"crossref","unstructured":"Infante, J., Rosalen, P.L., Lazarini, J.G., Franchin, M., and Alencar, S.M. (2016). Antioxidant and Anti-Inflammatory Activities of Unexplored Brazilian Native Fruits. PLoS ONE, 11.","key":"ref_3","DOI":"10.1371\/journal.pone.0152974"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/13880209.2018.1454480","article-title":"Brazilian medicinal plants with corroborated anti-inflammatory activities: A review","volume":"56","author":"Ribeiro","year":"2018","journal-title":"Pharm. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.jep.2007.03.005","article-title":"Chemical composition and anti-inflammatory activity of copaiba oils from Copaifera cearensis Huber ex Ducke, Copaifera reticulata Ducke and Copaifera multijuga Hayne\u2014A comparative study","volume":"112","author":"Rosas","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1002\/ptr.5992","article-title":"Antimicrobial activity of copaiba oil (Copaifera ssp.) on oral pathogens: Systematic review","volume":"32","author":"Diefenbach","year":"2018","journal-title":"Phytother. Res. PTR"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"122648","DOI":"10.1016\/j.ijpharm.2023.122648","article-title":"Aloe vera and copaiba oleoresin-loaded chitosan films for wound dressings: Microbial permeation, cytotoxicity, and in vivo proof of concept","volume":"634","author":"Genesi","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1002\/ptr.1295","article-title":"In vivo and in vitro studies on the anticancer activity of Copaifera multijuga hayne and its fractions","volume":"17","author":"Lima","year":"2003","journal-title":"Phytother. Res. PTR"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.fct.2005.08.011","article-title":"Genotoxicity evaluation of kaurenoic acid, a bioactive diterpenoid present in Copaiba oil","volume":"44","author":"Cavalcanti","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1590\/1414-431X20121423","article-title":"Kaurene diterpene induces apoptosis in U87 human malignant glioblastoma cells by suppression of anti-apoptotic signals and activation of cysteine proteases","volume":"46","author":"Tirapelli","year":"2013","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1055\/s-0030-1270904","article-title":"Botanical drugs, synergy, and network pharmacology: Forth and back to intelligent mixtures","volume":"77","author":"Gertsch","year":"2011","journal-title":"Planta Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.taap.2009.03.022","article-title":"Differential effect of pure isoflavones and soymilk on estrogen receptor activity in mice","volume":"237","author":"Rando","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_13","first-page":"2837","article-title":"Soy extract is more potent than genistein on tumor growth inhibition","volume":"28","author":"Kim","year":"2008","journal-title":"Anticancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.ijpharm.2018.11.054","article-title":"Chitosan\/Copaiba oleoresin films for would dressing application","volume":"555","author":"Debone","year":"2019","journal-title":"Int. J. Pharm."},{"doi-asserted-by":"crossref","unstructured":"Cimino, C., Maurel, O.M., Musumeci, T., Bonaccorso, A., Drago, F., Souto, E.M.B., Pignatello, R., and Carbone, C. (2021). Essential Oils: Pharmaceutical Applications and Encapsulation Strategies into Lipid-Based Delivery Systems. Pharmaceutics, 13.","key":"ref_15","DOI":"10.3390\/pharmaceutics13030327"},{"doi-asserted-by":"crossref","unstructured":"Blanco-Llamero, C., Galindo-Camacho, R.M., Fonseca, J., Santini, A., Senorans, F.J., and Souto, E.B. (2022). Development of Lipid Nanoparticles Containing Omega-3-Rich Extract of Microalga Nannochlorpsis gaditana. Foods, 11.","key":"ref_16","DOI":"10.3390\/foods11233749"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1208\/s12249-018-1217-7","article-title":"In vitro SPF and Photostability Assays of Emulsion Containing Nanoparticles with Vegetable Extracts Rich in Flavonoids","volume":"20","author":"Cefali","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.addr.2011.06.017","article-title":"Activation of complement by therapeutic liposomes and other lipid excipient-based therapeutic products: Prediction and prevention","volume":"63","author":"Szebeni","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.ejpb.2012.12.021","article-title":"Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity","volume":"84","author":"Biswas","year":"2013","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.addr.2011.05.017","article-title":"Lymphatic drug delivery using engineered liposomes and solid lipid nanoparticles","volume":"63","author":"Cai","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ejps.2013.06.012","article-title":"Silymarin loaded liposomes for hepatic targeting: In vitro evaluation and HepG2 drug uptake","volume":"50","author":"Elmowafy","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.addr.2007.04.009","article-title":"Parasitic diseases: Liposomes and polymeric nanoparticles versus lipid nanoparticles","volume":"59","author":"Date","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/j.msec.2016.11.014","article-title":"Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy","volume":"71","author":"Wang","year":"2017","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08982104.2012.708934","article-title":"Impact of PEGylation on biodistribution and tumor accumulation of Lipid-Mu peptide-DNA","volume":"23","author":"Bai","year":"2013","journal-title":"J. Liposome Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1177\/030089160308900302","article-title":"From conventional to stealth liposomes: A new frontier in cancer chemotherapy","volume":"89","author":"Cattel","year":"2003","journal-title":"Tumori"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.2174\/1567201815666180518125839","article-title":"Optimizing Antitumor Efficacy and Adverse Effects of Pegylated Liposomal Doxorubicin by Scheduled Plasmapheresis: Impact of Timing and Dosing","volume":"15","author":"Ngoune","year":"2018","journal-title":"Curr. Drug Deliv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.ejps.2013.03.007","article-title":"Complement activation by PEGylated liposomes containing prednisolone","volume":"49","author":"Nemes","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.ejpb.2012.02.007","article-title":"Application of different methods to formulate PEG-liposomes of oxaliplatin: Evaluation in vitro and in vivo","volume":"81","author":"Zalba","year":"2012","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jconrel.2010.03.007","article-title":"Improved tumor-targeting drug delivery and therapeutic efficacy by cationic liposome modified with truncated bFGF peptide","volume":"145","author":"Chen","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"118953","DOI":"10.1016\/j.ijpharm.2019.118953","article-title":"Synthesis, structure-activity relationship and biological evaluation of tetracationic gemini Dabco-surfactants for transdermal liposomal formulations","volume":"575","author":"Pashirova","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.colsurfb.2018.07.049","article-title":"Mixed cationic liposomes for brain delivery of drugs by the intranasal route: The acetylcholinesterase reactivator 2-PAM as encapsulated drug model","volume":"171","author":"Pashirova","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/jbm.a.30654","article-title":"Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum","volume":"77","author":"Kohane","year":"2006","journal-title":"J. Biomed. Mater. Res. Part A"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1039\/C1FO10181A","article-title":"Encapsulation of polyphenolic grape seed extract in polymer-coated liposomes","volume":"3","author":"Gibis","year":"2012","journal-title":"Food Funct."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1111\/jphp.13006","article-title":"Paclitaxel delivery system based on poly(lactide-co-glycolide) microparticles and chitosan thermo-sensitive gel for mammary adenocarcinoma treatment","volume":"70","author":"Pesoa","year":"2018","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_35","first-page":"155","article-title":"Solid lipid nanoparticles containing copaiba oil and allantoin: Development and role of nanoencapsulation on the antifungal activity","volume":"70","author":"Svetlichny","year":"2015","journal-title":"Die Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.msec.2015.11.034","article-title":"Design and characterization of chitosan\/zeolite composite films \u2014 Effect of zeolite type and zeolite dose on the film properties","volume":"60","author":"Barbosa","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/08982104.2011.573793","article-title":"Evaluation of thermal-oxidative stability and antiglioma activity of Zanthoxylum tingoassuiba essential oil entrapped into multi- and unilamellar liposomes","volume":"22","author":"Detoni","year":"2012","journal-title":"J. Liposome Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3816\/CLML.2011.n.005","article-title":"Efficacy and safety of pegylated liposomal Doxorubicin in combination with bortezomib for multiple myeloma: Effects of adverse prognostic factors on outcome","volume":"11","author":"Sonneveld","year":"2011","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jconrel.2012.03.020","article-title":"Doxil\u00ae-the first FDA-approved nano-drug: Lessons learned","volume":"160","author":"Barenholz","year":"2012","journal-title":"J. Control. Release"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1007\/s13346-020-00797-2","article-title":"Bioactive compounds of Copaifera sp. impregnated into three-dimensional gelatin dressings","volume":"10","author":"Pascoal","year":"2020","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.supflu.2017.02.012","article-title":"Copaiba oil-loaded commercial wound dressings using supercritical CO2: A potential alternative topical antileishmanial treatment","volume":"129","author":"Pascoal","year":"2017","journal-title":"J. Supercrit. Fluids"},{"doi-asserted-by":"crossref","unstructured":"Bangham, A.D., Standish, M.M., and Watkins, J.C. (1965). Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol., 13.","key":"ref_42","DOI":"10.1016\/S0022-2836(65)80093-6"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0887-2333(94)90156-2","article-title":"Alterations in the glial fibrillary acidic protein content of primary astrocyte cultures for evaluation of glial cell toxicity","volume":"8","author":"Cookson","year":"1994","journal-title":"Toxicol. Vitr. Int. J. Publ. Assoc. BIBRA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.vetimm.2006.05.006","article-title":"Astroglial cells in primary culture: A valid model to study Neospora caninum infection in the CNS","volume":"113","author":"Pinheiro","year":"2006","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"ref_46","first-page":"306","article-title":"Cytotoxic effects of catechol to neuroblastoma N2a cells","volume":"27","author":"Lima","year":"2008","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"297","DOI":"10.2174\/156720107782151269","article-title":"Liposomal drug delivery systems: An update review","volume":"4","author":"Samad","year":"2007","journal-title":"Curr. Drug Deliv."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2147\/IJN.S1253","article-title":"Tumor targeting using liposomal antineoplastic drugs","volume":"3","author":"Huwyler","year":"2008","journal-title":"Int. J. Nanomed."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"075604","DOI":"10.1088\/1361-6528\/aaf3f8","article-title":"Development of a novel drug targeting delivery system for cervical cancer therapy","volume":"30","author":"Xiao","year":"2019","journal-title":"Nanotechnology"},{"doi-asserted-by":"crossref","unstructured":"da Trindade, R., da Silva, J.K., and Setzer, W.N. (2018). Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology. Int. J. Mol. Sci., 19.","key":"ref_50","DOI":"10.3390\/ijms19051511"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"15768","DOI":"10.1021\/jacs.7b07747","article-title":"Triggered Release from Lipid Bilayer Vesicles by an Artificial Transmembrane Signal Transduction System","volume":"139","author":"Langton","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.1016\/j.biomaterials.2009.07.033","article-title":"The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes","volume":"30","author":"Yang","year":"2009","journal-title":"Biomaterials"},{"doi-asserted-by":"crossref","unstructured":"Abrao, F., de Araujo Costa, L.D., Alves, J.M., Senedese, J.M., de Castro, P.T., Ambrosio, S.R., Veneziani, R.C., Bastos, J.K., Tavares, D.C., and Martins, C.H. (2015). Copaifera langsdorffii oleoresin and its isolated compounds: Antibacterial effect and antiproliferative activity in cancer cell lines. BMC Complement. Altern. Med., 15.","key":"ref_53","DOI":"10.1186\/s12906-015-0961-4"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"306","DOI":"10.3109\/13880209.2010.515595","article-title":"Pharmacological evaluation of Copaifera multijuga oil in rats","volume":"49","author":"Kobayashi","year":"2011","journal-title":"Pharm. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.foodchem.2015.11.093","article-title":"Polyphenols, antioxidants, and antimutagenic effects of Copaifera langsdorffii fruit","volume":"197 (Pt B)","author":"Batista","year":"2016","journal-title":"Food Chem."},{"key":"ref_56","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_57","doi-asserted-by":"crossref","first-page":"12320","DOI":"10.1002\/anie.201403036","article-title":"Engineered nanoparticles for drug delivery in cancer therapy","volume":"53","author":"Sun","year":"2014","journal-title":"Angew. Chem. (Int. Ed. Engl.)"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.jep.2008.06.033","article-title":"Antineoplasic activity of Copaifera multijuga oil and fractions against ascitic and solid Ehrlich tumor","volume":"119","author":"Fontes","year":"2008","journal-title":"J. Ethnopharmacol."},{"doi-asserted-by":"crossref","unstructured":"Irrera, N., D\u2019Ascola, A., Pallio, G., Bitto, A., Mannino, F., Arcoraci, V., Rottura, M., Ieni, A., Minutoli, L., and Metro, D. (2020). \u03b2-Caryophyllene Inhibits Cell Proliferation through a Direct Modulation of CB2 Receptors in Glioblastoma Cells. Cancers, 12.","key":"ref_59","DOI":"10.3390\/cancers12041038"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"872394","DOI":"10.1155\/2012\/872394","article-title":"\u03b2-Caryophyllene, a Compound Isolated from the Biblical Balm of Gilead (Commiphora gileadensis), Is a Selective Apoptosis Inducer for Tumor Cell Lines","volume":"2012","author":"Amiel","year":"2012","journal-title":"Evid. -Based Complement. Altern. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.2147\/IJN.S117210","article-title":"Getting into the brain: Liposome-based strategies for effective drug delivery across the blood-brain barrier","volume":"11","author":"Vieira","year":"2016","journal-title":"Int. J. Nanomed."},{"unstructured":"Kumar, L., and Pathak, Y.Y. (2022). Nanocarriers for Drug-Targeting Brain Tumors, Elsevier.","key":"ref_62"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ejps.2015.08.016","article-title":"Co-encapsulation of imiquimod and copaiba oil in novel nanostructured systems: Promising formulations against skin carcinoma","volume":"79","author":"Venturini","year":"2015","journal-title":"Eur. J. Pharm. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:38:19Z","timestamp":1760121499000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/15\/2\/671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":63,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["pharmaceutics15020671"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics15020671","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}