{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:39:13Z","timestamp":1793799553614,"version":"4.6.1"},"reference-count":99,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T00:00:00Z","timestamp":1726099200000},"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>Skin cancer is a high-incidence complex disease, representing a significant challenge to public health, with conventional treatments often having limited efficacy and severe side effects. Nanocarrier-based systems provide a controlled, targeted, and efficacious methodology for the delivery of therapeutic molecules, leading to enhanced therapeutic efficacy, the protection of active molecules from degradation, and reduced adverse effects. These features are even more relevant in dual-loaded nanosystems, with the encapsulated drug molecules leading to synergistic antitumor effects. This review examines the potential of improving the treatment of skin cancer through dual-loaded liposomal systems. The performed analysis focused on the characterization of the developed liposomal formulations\u2019 particle size, polydispersity index, zeta potential, encapsulation efficiency, drug release, and in vitro and\/or in vivo therapeutic efficacy and safety. The combination of therapeutic agents such as doxorubicin, 5-fluorouracil, paclitaxel, cetuximab, celecoxib, curcumin, resveratrol, quercetin, bufalin, hispolon, ceramide, DNA, STAT3 siRNA, Bcl-xl siRNA, Aurora-A inhibitor XY-4, 1-Methyl-tryptophan, and cytosine\u2013phosphate\u2013guanosine anionic peptide led to increased and targeted anticancer effects, having relevant complementary effects as well, including antioxidant, anti-inflammatory, and immunomodulatory activities, all relevant in skin cancer pathophysiology. The substantial potential of co-loaded liposomal systems as highly promising for advancing skin cancer treatment is demonstrated.<\/jats:p>","DOI":"10.3390\/pharmaceutics16091200","type":"journal-article","created":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T06:31:40Z","timestamp":1726122700000},"page":"1200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Improving Skin Cancer Treatment by Dual Drug Co-Encapsulation into Liposomal Systems\u2014An Integrated Approach towards Anticancer Synergism and Targeted Delivery"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3356-3755","authenticated-orcid":false,"given":"Margarida","family":"Corte-Real","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Veiga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2710-6000","authenticated-orcid":false,"given":"Ana Cl\u00e1udia","family":"Paiva-Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-4894","authenticated-orcid":false,"given":"Patr\u00edcia C.","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal"},{"name":"REQUIMTE\/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Av. Infante D. Henrique, 6200-506 Covilh\u00e3, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15287","DOI":"10.3390\/ijms150915287","article-title":"Dual Targeting Biomimetic Liposomes for Paclitaxel\/DNA Combination Cancer Treatment","volume":"15","author":"Liu","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_3","unstructured":"(2024, July 20). Global Cancer Burden Growing, amidst Mounting Need for Services. Available online: https:\/\/www.who.int\/news\/item\/01-02-2024-global-cancer-burden-growing--amidst-mounting-need-for-services."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Woo, Y.R., Cho, S.H., Lee, J.D., and Kim, H.S. (2022). The Human Microbiota and Skin Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031813"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jare.2021.06.014","article-title":"Skin Cancer Biology and Barriers to Treatment: Recent Applications of Polymeric Micro\/Nanostructures","volume":"36","author":"Khan","year":"2022","journal-title":"J. Adv. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12943-022-01708-4","article-title":"Advancements in Nanoparticle-Based Treatment Approaches for Skin Cancer Therapy","volume":"22","author":"Zeng","year":"2023","journal-title":"Mol. Cancer"},{"key":"ref_7","unstructured":"(2024, July 20). Skin Cancer\u2014IARC. Available online: https:\/\/www.iarc.who.int\/cancer-type\/skin-cancer\/."},{"key":"ref_8","unstructured":"(2024, July 20). Skin Cancer Facts & Statistics\u2014The Skin Cancer Foundation. Available online: https:\/\/www.skincancer.org\/skin-cancer-information\/skin-cancer-facts\/."},{"key":"ref_9","unstructured":"(2024, July 20). Skin Cancer Statistics. World Cancer Research Fund International. Available online: https:\/\/www.wcrf.org\/cancer-trends\/skin-cancer-statistics\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","unstructured":"(2024, July 20). Treatment Glossary\u2014The Skin Cancer Foundation. Available online: https:\/\/www.skincancer.org\/treatment-resources\/treatment-glossary\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.2147\/IJN.S147759","article-title":"Co-Delivery of Aurora-A Inhibitor XY-4 and Bcl-Xl SiRNA Enhances Antitumor Efficacy for Melanoma Therapy","volume":"13","author":"Duan","year":"2018","journal-title":"Int. J. Nanomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"153","DOI":"10.4149\/neo_2024_240315N118","article-title":"Nanocomposite Hydrogels in Skin Cancer Medicine","volume":"71","author":"Balintova","year":"2024","journal-title":"Neoplasma"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/09205063.2022.2054399","article-title":"Recent Advances in Nanotechnology Based Combination Drug Therapy for Skin Cancer","volume":"33","author":"Kumari","year":"2022","journal-title":"J. Biomater. Sci. Polym. Ed."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1208\/s12249-020-01846-2","article-title":"Co-Delivery of Hispolon and Doxorubicin Liposomes Improves Efficacy Against Melanoma Cells","volume":"21","author":"Aldawsari","year":"2020","journal-title":"AAPS PharmSciTech"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.ijpharm.2016.09.014","article-title":"Effect of Quercetin and Resveratrol Co-Incorporated in Liposomes against Inflammatory\/Oxidative Response Associated with Skin Cancer","volume":"513","author":"Caddeo","year":"2016","journal-title":"Int. J. Pharm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1208\/s12249-019-1316-0","article-title":"Co-Delivery of Doxorubicin and Ceramide in a Liposomal Formulation Enhances Cytotoxicity in Murine B16BL6 Melanoma Cell Lines","volume":"20","author":"Chen","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_18","unstructured":"(2024, July 05). Immune Checkpoint Inhibitors\u2014NCI, Available online: https:\/\/www.cancer.gov\/about-cancer\/treatment\/types\/immunotherapy\/checkpoint-inhibitors."},{"key":"ref_19","first-page":"5683","article-title":"Immunoliposome Co-Delivery of Bufalin and Anti-CD40 Antibody Adjuvant Induces Synergetic Therapeutic Efficacy against Melanoma","volume":"9","author":"Li","year":"2014","journal-title":"Int. J. Nanomed."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ataide, J.A., Coco, J.C., dos Santos, \u00c9.M., Beraldo-Araujo, V., Silva, J.R.A., de Castro, K.C., Lopes, A.M., Filipczak, N., Yalamarty, S.S.K., and Torchilin, V.P. (2023). Co-Encapsulation of Drugs for Topical Application\u2014A Review. Molecules, 28.","DOI":"10.3390\/molecules28031449"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Marek-Jozefowicz, L., Nedoszytko, B., Grochocka, M., \u017bmijewski, M.A., Czajkowski, R., Cuba\u0142a, W.J., and Slominski, A.T. (2023). Molecular Mechanisms of Neurogenic Inflammation of the Skin. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24055001"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cell.2020.05.039","article-title":"Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma","volume":"182","author":"Ji","year":"2020","journal-title":"Cell"},{"key":"ref_23","first-page":"339","article-title":"Basal Cell and Cutaneous Squamous Cell Carcinomas: Diagnosis and Treatment","volume":"102","author":"Firnhaber","year":"2020","journal-title":"Am. Fam. Physician"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13005-016-0106-0","article-title":"Basal Cell Carcinoma, Squamous Cell Carcinoma and Melanoma of the Head and Face","volume":"12","author":"Feller","year":"2016","journal-title":"Head Face Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1177\/0194599811400711","article-title":"Curcumin Inhibits Skin Squamous Cell Carcinoma Tumor Growth In Vivo","volume":"145","author":"Phillips","year":"2011","journal-title":"Otolaryngol.\u2013Head Neck Surg."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Filipczak, N., Jaromin, A., Piwoni, A., Mahmud, M., Sarisozen, C., Torchilin, V., and Gubernator, J. (2019). A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells. Cancers, 11.","DOI":"10.3390\/cancers11121982"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejpb.2023.02.002","article-title":"Nanodelivery Systems for Cutaneous Melanoma Treatment","volume":"184","author":"Pereira","year":"2023","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Beiu, C., Giurcaneanu, C., Grumezescu, A.M., Holban, A.M., Popa, L.G., and Mihai, M.M. (2020). Nanosystems for Improved Targeted Therapies in Melanoma. J. Clin. Med., 9.","DOI":"10.3390\/jcm9020318"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1053\/j.gastro.2010.02.005","article-title":"Vascular Endothelial Growth Factor and Epidermal Growth Factor Signaling Pathways as Therapeutic Targets for Colorectal Cancer","volume":"138","author":"Winder","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_30","first-page":"2585","article-title":"Overview of the STAT-3 Signaling Pathway in Cancer and the Development of Specific Inhibitors","volume":"19","author":"Gu","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7055","DOI":"10.18632\/oncotarget.6855","article-title":"STAT3-Survivin Signaling Mediates a Poor Response to Radiotherapy in HER2-Positive Breast Cancers","volume":"7","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100821","DOI":"10.1016\/j.neo.2022.100821","article-title":"Hypoxia Induces Docetaxel Resistance in Triple-Negative Breast Cancer via the HIF-1\u03b1\/MiR-494\/Survivin Signaling Pathway","volume":"32","author":"Li","year":"2022","journal-title":"Neoplasia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1177\/10915818211014170","article-title":"Survivin Promoter-Driven DFF40 Gene Expression Sensitizes Melanoma Cancer Cells to Chemotherapy","volume":"40","author":"Minaiyan","year":"2021","journal-title":"Int. J. Toxicol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/jid.2011.279","article-title":"Survivin: A Dual Player in Healthy and Diseased Skin","volume":"132","author":"Dallaglio","year":"2012","journal-title":"J. Investig. Dermatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1111\/j.1600-0625.2011.01273.x","article-title":"Della Survivin in Skin Pathologies","volume":"20","author":"Bongiovanni","year":"2011","journal-title":"Exp. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/annonc\/mdx702","article-title":"Overview of Current Systemic Management of EGFR-Mutant NSCLC","volume":"29","author":"Hsu","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jconrel.2018.05.038","article-title":"Skin Cancer Treatment Effectiveness Is Improved by Iontophoresis of EGFR-Targeted Liposomes Containing 5-FU Compared with Subcutaneous Injection","volume":"283","author":"Petrilli","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1080\/15384101.2021.1922806","article-title":"Targeting Cell Cycle Regulation via the G2-M Checkpoint for Synthetic Lethality in Melanoma","volume":"20","author":"Barnaba","year":"2021","journal-title":"Cell Cycle"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3876","DOI":"10.1158\/1078-0432.CCR-20-4050","article-title":"Phase I\u2013II Open-Label Multicenter Study of Palbociclib \u00fe Vemurafenib in BRAFV600MUT Metastatic Melanoma Patients: Uncovering CHEK2 as a Major Response Mechanism","volume":"27","author":"Louveau","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez, I., Saavedra, E., Del Rosario, H., Perdomo, J., Quintana, J., Prencipe, F., Oliva, P., Romagnoli, R., and Est\u00e9vez, F. (2021). Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413462"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpharm.2015.04.056","article-title":"Ultradeformable Liposomes as Multidrug Carrier of Resveratrol and 5-Fluorouracil for Their Topical Delivery","volume":"489","author":"Cosco","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_42","unstructured":"Wilbur, R.L. (2017). The Difference between Topical and Transdermal Medications, Gensco Pharma."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1016\/j.msec.2019.02.095","article-title":"Derma Roller\u00ae Microneedles-Mediated Transdermal Delivery of Doxorubicin and Celecoxib Co-Loaded Liposomes for Enhancing the Anticancer Effect","volume":"99","author":"Ahmed","year":"2019","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Champeau, M., Vignoud, S., Mortier, L., and Mordon, S. (2019). Photodynamic Therapy for Skin Cancer: How to Enhance Drug Penetration?. J. Photochem. Photobiol. B, 197.","DOI":"10.1016\/j.jphotobiol.2019.111544"},{"key":"ref_45","first-page":"1579","article-title":"Subcutaneous Administration of Anticancer Agents","volume":"34","author":"Leveque","year":"2014","journal-title":"Int. Inst. Anticancer Res."},{"key":"ref_46","first-page":"S20","article-title":"Healthcare Provider Administration of Biologics for Patients with Plaque Psoriasis: Literature Review and Clinical Considerations","volume":"16","author":"Brunner","year":"2023","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Silva, C.O., Pinho, J.O., Lopes, J.M., Almeida, A.J., Gaspar, M.M., and Reis, C. (2019). Current Trends in Cancer Nanotheranostics: Metallic, Polymeric, and Lipid-Based Systems. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11010022"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Song, M., Liu, C., Chen, S., and Zhang, W. (2021). Nanocarrier-Based Drug Delivery for Melanoma Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041873"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Adamus-Grabicka, A.A., Hikisz, P., and Sikora, J. (2024). Nanotechnology as a Promising Method in the Treatment of Skin Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25042165"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.bmt.2023.09.001","article-title":"Review of the Efficacy of Nanoparticle-Based Drug Delivery Systems for Cancer Treatment","volume":"5","author":"Elumalai","year":"2024","journal-title":"Biomed. Technol."},{"key":"ref_51","first-page":"666","article-title":"Nanomedicine: Advantages and Disadvantages of Nanomedicine","volume":"14","author":"Soliman","year":"2023","journal-title":"Rev. J. Nanomed. Nanotechnol."},{"key":"ref_52","unstructured":"Lambros, M.P., Huang, Y., and Mulamalla, H.C. (2012). Targeted Liposomes in Cancer Therapy. (US9808425B2), U.S. Patent."},{"key":"ref_53","unstructured":"Hong, K., Drummond, D.C., and Kirpotin, D. (2015). Liposomes Useful for Drug Delivery. (US20160030341A1), U.S. Patent."},{"key":"ref_54","unstructured":"Tan, J., Jiang, L., Chang, T., and Zhou, Z. (2012). Paclitaxel Ethosome Gel and Preparation Method Thereof. (CN102579323A)."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7627","DOI":"10.2147\/IJN.S263516","article-title":"Development, Characterization and Use of Liposomes as Amphipathic Transporters of Bioactive Compounds for Melanoma Treatment and Reduction of Skin Inflammation: A Review","volume":"15","author":"Lee","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102757","DOI":"10.1016\/j.cis.2022.102757","article-title":"Liposomes as Biocompatible and Smart Delivery Systems\u2014The Current State","volume":"309","author":"Dymek","year":"2022","journal-title":"Adv. Colloid. Interface Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"178462","DOI":"10.1016\/j.tca.2019.178462","article-title":"Simultaneous Encapsulation of Hydrophilic and Lipophilic Molecules in Liposomes of DSPC","volume":"687","year":"2020","journal-title":"Thermochim. Acta"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.colsurfb.2018.04.033","article-title":"Optimizing Liposomes for Delivery of Bowman-Birk Protease Inhibitors\u2014Platforms for Multiple Biomedical Applications","volume":"167","author":"Joanitti","year":"2018","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Guimar\u00e3es, D., Noro, J., Loureiro, A., Lager, F., Renault, G., Cavaco-Paulo, A., and Nogueira, E. (2020). Increased Encapsulation Efficiency of Methotrexate in Liposomes for Rheumatoid Arthritis Therapy. Biomedicines, 8.","DOI":"10.3390\/biomedicines8120630"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1556-276X-8-102","article-title":"Liposome: Classification, Preparation, and Applications","volume":"8","author":"Akbarzadeh","year":"2013","journal-title":"Nanoscale Res. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"120571","DOI":"10.1016\/j.ijpharm.2021.120571","article-title":"Design of Liposomes as Drug Delivery System for Therapeutic Applications","volume":"601","author":"Nogueira","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e09394","DOI":"10.1016\/j.heliyon.2022.e09394","article-title":"Liposomes: Structure, Composition, Types, and Clinical Applications","volume":"8","author":"Nsairat","year":"2022","journal-title":"Heliyon"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Franco, M.S., Gomes, E.R., Roque, M.C., and Oliveira, M.C. (2021). Triggered Drug Release from Liposomes: Exploiting the Outer and Inner Tumor Environment. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.623760"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.mattod.2015.11.025","article-title":"Tumor Microenvironment and Intracellular Signal-Activated Nanomaterials for Anticancer Drug Delivery","volume":"19","author":"Mo","year":"2016","journal-title":"Mater. Today"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Souto, E.B., Macedo, A.S., Dias-Ferreira, J., Cano, A., Zieli\u0144ska, A., and Matos, C.M. (2021). Elastic and Ultradeformable Liposomes for Transdermal Delivery of Active Pharmaceutical Ingredients (APIs). Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189743"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"421","DOI":"10.2174\/1567201817666201014144708","article-title":"Iontophoretic Mediated Intraarticular Delivery of Deformable Liposomes of Diclofenac Sodium","volume":"18","author":"Vanaja","year":"2021","journal-title":"Curr. Drug Deliv."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Hmingthansanga, V., Singh, N., Banerjee, S., Manickam, S., Velayutham, R., and Natesan, S. (2022). Improved Topical Drug Delivery: Role of Permeation Enhancers and Advanced Approaches. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122818"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Danaei, M., Dehghankhold, M., Ataei, S., Hasanzadeh Davarani, F., Javanmard, R., Dokhani, A., Khorasani, S., and Mozafari, M.R. (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10.","DOI":"10.3390\/pharmaceutics10020057"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2179129","DOI":"10.1080\/10717544.2023.2179129","article-title":"A Comprehensive Review on Recent Nanosystems for Enhancing Antifungal Activity of Fenticonazole Nitrate from Different Routes of Administration","volume":"30","author":"Ahmed","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"N\u00e9meth, Z., Cs\u00f3ka, I., Semnani Jazani, R., Sipos, B., Haspel, H., Kozma, G., K\u00f3nya, Z., and Dob\u00f3, D.G. (2022). Quality by Design-Driven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091798"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"34614","DOI":"10.1039\/C8RA07069E","article-title":"Design and Production of Hybrid Nanoparticles with Polymeric-Lipid Shell\u2013Core Structures: Conventional and next-Generation Approaches","volume":"8","author":"Bochicchio","year":"2018","journal-title":"RSC Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e23365","DOI":"10.1590\/s2175-97902023e23365","article-title":"Challenges in Estimating the Encapsulation Efficiency of Proteins in Polymersomes\u2014Which Is the Best Method?","volume":"59","author":"Monteiro","year":"2023","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Adepu, S., Ramakrishna, S., Costa-Pinto, R., and Oliveira, A.L. (2021). Controlled Drug Delivery Systems: Current Status and Future Directions. Molecules, 26.","DOI":"10.3390\/molecules26195905"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-L\u00e1zaro, L., Mart\u00edn-Sabroso, C., Aparicio-Blanco, J., and Torres-Su\u00e1rez, A.I. (2024). Assessment of In Vitro Release Testing Methods for Colloidal Drug Carriers: The Lack of Standardized Protocols. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010103"},{"key":"ref_75","first-page":"304757","article-title":"A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms","volume":"2014","year":"2014","journal-title":"Adv. Pharm."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"113795","DOI":"10.1016\/j.addr.2021.05.005","article-title":"An Overview of in Vitro, Ex Vivo and in Vivo Models for Studying the Transport of Drugs across Intestinal Barriers","volume":"175","author":"Xu","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1208\/s12248-019-0325-y","article-title":"Targeting Cancer Via Resveratrol-Loaded Nanoparticles Administration: Focusing on In Vivo Evidence","volume":"21","author":"Santos","year":"2019","journal-title":"AAPS J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.canlet.2021.05.001","article-title":"Resveratrol for Cancer Therapy: Challenges and Future Perspectives","volume":"515","author":"Ren","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Skok, K., Zidari\u010d, T., Orthaber, K., Pristovnik, M., Kostev\u0161ek, N., Ro\u017eman, K.\u017d., \u0160turm, S., Gradi\u0161nik, L., Maver, U., and Maver, T. (2022). Novel Methacrylate-Based Multilayer Nanofilms with Incorporated FePt-Based Nanoparticles and the Anticancer Drug 5-Fluorouracil for Skin Cancer Treatment. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14040689"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1080\/1061186X.2016.1258567","article-title":"Co-Delivery of Curcumin and STAT3 SiRNA Using Deformable Cationic Liposomes to Treat Skin Cancer","volume":"25","author":"Jose","year":"2017","journal-title":"J. Drug Target."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1208\/s12249-017-0833-y","article-title":"Effective Skin Cancer Treatment by Topical Co-Delivery of Curcumin and STAT3 SiRNA Using Cationic Liposomes","volume":"19","author":"Jose","year":"2018","journal-title":"AAPS PharmSciTech"},{"key":"ref_82","unstructured":"Aggarwal, B.B., Kumar, A., and Bharti, A.C. (2024, May 02). (PDF) Anticancer Potential of Curcumin: Preclinical and Clinical Studies. Available online: https:\/\/www.researchgate.net\/publication\/10818418_Anticancer_Potential_of_Curcumin_Preclinical_and_Clinical_Studies."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/ardp.200900319","article-title":"Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical Trials","volume":"343","author":"Shehzad","year":"2010","journal-title":"Arch. Pharm."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1545","DOI":"10.1017\/S0007114509993667","article-title":"Curcumin as a Therapeutic Agent: The Evidence from in Vitro, Animal and Human Studies","volume":"103","author":"Epstein","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1172\/JCI22800","article-title":"Stat3 Is Required for the Development of Skin Cancer","volume":"114","author":"Pedranzini","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1038\/nrc2734","article-title":"STATs in Cancer Inflammation and Immunity: A Leading Role for STAT3","volume":"9","author":"Yu","year":"2009","journal-title":"Nat. Rev. Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/bjc.2015.233","article-title":"The Role of JAK\/STAT Signalling in the Pathogenesis, Prognosis and Treatment of Solid Tumours","volume":"113","author":"Thomas","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2000","DOI":"10.1038\/sj.onc.1205260","article-title":"Constitutive Stat3 Activity Up-Regulates VEGF Expression and Tumor Angiogenesis","volume":"21","author":"Niu","year":"2002","journal-title":"Oncogene"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1208\/s12249-014-0254-0","article-title":"Enhancement of Oral Bioavailability of Curcumin by a Novel Solid Dispersion System","volume":"16","author":"Hu","year":"2015","journal-title":"AAPS PharmSciTech"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"5972","DOI":"10.3390\/molecules17055972","article-title":"Preparation of Curcumin-Loaded Liposomes and Evaluation of Their Skin Permeation and Pharmacodynamics","volume":"17","author":"Chen","year":"2012","journal-title":"Molecules"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"10815","DOI":"10.1039\/c3ra46396f","article-title":"Curcumin, a Promising Anti-Cancer Therapeutic: A Review of Its Chemical Properties, Bioactivity and Approaches to Cancer Cell Delivery","volume":"4","author":"Salem","year":"2014","journal-title":"RSC Adv."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.drudis.2011.09.009","article-title":"Curcumin Nanoformulations: A Future Nanomedicine for Cancer","volume":"17","author":"Yallapu","year":"2012","journal-title":"Drug Discov. Today"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ijpharm.2013.06.052","article-title":"Selection of High Efficient Transdermal Lipid Vesicle for Curcumin Skin Delivery","volume":"454","author":"Zhao","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"10226","DOI":"10.1039\/c2sm26614h","article-title":"Structural Analysis of \u201c\u2018Flexible\u2019\u201d Liposome Formulations: New Insights into the Skin-Penetrating Ability of Soft Nanostructures","volume":"8","author":"Ogunsola","year":"2012","journal-title":"Soft Matter"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"15816","DOI":"10.1073\/pnas.1016152108","article-title":"Delivery of SiRNA and Other Macromolecules into Skin and Cells Using a Peptide Enhancer","volume":"108","author":"Hsu","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1208\/s12248-010-9210-4","article-title":"Delivery of SiRNA Therapeutics: Barriers and Carriers","volume":"12","author":"Wang","year":"2010","journal-title":"AAPS J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1039\/D1TB00256B","article-title":"Co-Delivery of Anionic Epitope\/CpG Vaccine and IDO Inhibitor by Self-Assembled Cationic Liposomes for Combination Melanoma Immunotherapy","volume":"9","author":"Su","year":"2021","journal-title":"J. Mater. Chem. B"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Fulton, M.D., and Najahi-Missaoui, W. (2023). Liposomes in Cancer Therapy: How Did We Start and Where Are We Now. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24076615"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s12668-022-00941-x","article-title":"A Comprehensive Review on Novel Liposomal Methodologies, Commercial Formulations, Clinical Trials and Patents","volume":"12","author":"Andra","year":"2022","journal-title":"Bionanoscience"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/9\/1200\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:54:35Z","timestamp":1760111675000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/9\/1200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,12]]},"references-count":99,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["pharmaceutics16091200"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16091200","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,12]]}}}