Transdermal Drug Delivery in Oncology Charting the Road Ahead

Year 2025, Volume: 45 Issue: 3, 286 - 299, 01.09.2025

Bhushan Rane , Sanskruti Gawade

https://doi.org/10.52794/hujpharm.1611956

Abstract

Transdermal drug administration is a method of administering medication through the skin that is non-intrusive, offering an innovative and hopeful alternative to traditional oral and injection methods. Advancements in skin penetration technology have enabled the transdermal administration of various anticancer medications, including lipophilic or hydrophilic compounds, offering a new approach to cancer treatment. Research has explored innovative platforms for cancer treatment, such as erythrocytes, vesicles, and exosomes. The most efficient approach is the transdermal drug delivery system. This review investigates various transdermal delivery techniques beyond the pharmaceutical sector in relation to cancer treatment. Techniques include iontophoresis, electroporation, sonophoresis, microneedles, transdermal patches, or vesicular systems like liposomes, niosomes, transferosomes, ethosomes, transethosomes, nanoparticles, carbon nanotubes, quantum dots, as well as nanofibers, which have been used to improve transdermal distribution and their use in cancer treatment. Additionally, a roadmap is presented to guide development strategies, highlighting the multiple applications of transdermal drug administration systems for cancer therapy.

Keywords

Transdermal drug delivery , Skin cancer , Breast cancer , Nanoparticles , Vesicular system.

Ethical Statement

NA

Supporting Institution

NIL

Project Number

NA

Thanks

We hereby acknowledge the Shri D D Vispute College of Pharmacy for all the facilities provided.

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2019;69(1):7–34. https://doi.org/10.3322/caac.21551
• 2. Chatzilakou E, Hu Y, Jiang N, Yetisen AK. Biosensors for melanoma skin cancer diagnostics. Biosens Bioelectron. 2024;250(116045):116045. https://doi.org/10.1016/j.bios.2024.116045
• 3. Brancaccio G, Balato A, Malvehy J, Puig S, Argenziano G, Kittler H. Artificial intelligence in skin cancer diagnosis: A reality check. J Invest Dermatol. 2024;144(3):492–9. https://doi.org/10.1016/j.jid.2023.10.004
• 4. Peña-Juárez MC, Guadarrama-Escobar OR, Escobar-Chávez JJ. Transdermal delivery systems for biomolecules. J Pharm Innov. 2022;17(2):319–32. http://doi.org/10.1007/s12247-020-09525-2
• 5. Giaquinto AN, Sung H, Miller KD, Kramer JL, Newman LA, Minihan A, et al. Breast cancer statistics. CA Cancer J Clin. 2022;72(6):524–41.http://doi.org/10.3322/caac.21754.
• 6. Britt KL, Cuzick J, Phillips KA. Key steps for effective breast cancer prevention. Nature Reviews Cancer. 2020 Aug 1;20(8):417–36. https://doi.org/10.1038/s41568-020-0266-x
• 7. Zhao Z, Ukidve A, Dasgupta A, Mitragotri S. Transdermal immunomodulation: Principles, advances and perspectives. Adv Drug Deliv Rev. 2018;127:3–19. http://doi.org/10.1016/j.addr.2018.03.010.
• 8. Babaie S, Bakhshayesh ARD, Ha JW, Hamishehkar H, Kim KH. Invasome: A novel nanocarrier for transdermal drug delivery. Nanomaterials (Basel) . 2020 ;10(2):341. https://doi.org/10.3390/nano10020341.
• 9. Keservani RK, Bandopadhyay S, Bandyopadhyay N, Sharma AK. Design and fabrication of transdermal/skin drug-delivery system. Academic Press. 2019;p. 131–78. https://doi.org/10.1016/b978-0-12-814487-9.00004-1
• 10. Yu Y Q, Yang X, Wu X F, Fan Y B. Enhancing permeation of drug molecules across the skin via delivery in nanocarriers: Novel strategies for effective transdermal applications. Front Bioeng Biotechnol. 2021;9. http://doi.org/10.3389/fbioe.2021.646554
• 11. Sabbagh F, Kim BS. Recent advances in polymeric transdermal drug delivery systems. J Control Release.2022;341:132–46. https://doi.org/10.22159/ijap.2024v16i2.49950
• 12. De Leo V, Maurelli AM, Giotta L, Catucci L. Liposomes containing nanoparticles: preparation and applications. Colloids Surf B Biointerfaces.2022;218(112737):112737. http://doi.org/10.1016/j.colsurfb.2022.112737
• 13. Roxhed N, Gasser TC, Griss P, Holzapfel GA, Stemme G. Penetration-enhanced ultrasharp microneedles and prediction on skin interaction for efficient transdermal drug delivery. J Microelectromech Syst. 2007;16(6):1429–40. https://doi.org/10.1109/JMEMS.2007.907461 .
• 14. Byrne CM, Thompson JF. Role of electrochemotherapy in the treatment of metastatic melanoma and other metastatic and primary skin tumors. Expert Rev Anticancer Ther. 2006;6(5):671–8. http://doi.org/10.1586/14737140.6.5.671
• 15. Cosco D, Paolino D, Muzzalupo R, Celia C, Citraro R, Caponio D, et al. Novel PEG-coated niosomes based on bola-surfactant as drug carriers for 5-fluorouracil. Biomed Microdevices . 2009;11(5):1115–25. http://doi.org/10.1007/s10544-009-9328-2.
• 16. Xi H, Yang Y, Zhao D, Fang L, Sun L, Mu L, et al. Transdermal patches for site-specific delivery of anastrozole: In vitro and local tissue disposition evaluation. International Journal of Pharmaceutics. 2010;391(1-2):73–8. http://doi.org/10.1208/s12249-010-9465-1
• 17. Husseini GA, Pitt WG. Ultrasonic-activated micellar drug delivery for cancer treatment. J Pharm Sci . 2009;98(3):795–811. http://doi.org/10.1002/jps.21444
• 18. Jin Y, Ren X, Wang W, Ke L, Ning E, Du L, et al. A 5-fluorouracil-loaded pH-responsive dendrimer nanocarrier for tumor targeting. Int J Pharm . 2011;420(2):378–84. http://doi.org/10.1016/j.ijpharm.2011.08.053
• 19. Sarwa K, Suresh PK, Debnath M, Ahmad M. Tamoxifen citrate loaded ethosomes for transdermal drug delivery system: preparation and characterization. Curr Drug Deliv . 2013;10(4):466–76. http://doi.org/10.2174/1567201811310040011
• 20. Iqbal MA, Md S, Sahni JK, Baboota S, Dang S, Ali J. Nanostructured lipid carriers system: Recent advances in drug delivery. J Drug Target. 2012;20(10):813–30. http://doi.org/10.3109/1061186x.2012.716845
• 21. Mahmood S, Taher M, Mandal UK. Experimental design and optimization of raloxifene hydrochloride loaded nanotransfersomes for transdermal application. Int J Nanomedicine. 2014;9:4331–46. http://doi.org/10.2147/IJN.S65408
• 22. Lu B, Xiong S-B, Yang H, Yin X-D, Chao R-B. Solid lipid nanoparticles of mitoxantrone for local injection against breast cancer and its lymph node metastases. Eur J Pharm Sci . 2006;28(1–2):86–95. http://doi.org/10.1016/j.ejps.2006.01.001
• 23. Iannazzo D, Pistone A, Salamò M, Galvagno S, Romeo R, Giofré SV, et al. Graphene quantum dots for cancer targeted drug delivery. Int J Pharm. 2017;518(1–2):185–92. https://doi.org/10.1016/j.ijpharm.2016.12.060
• 24. Akhtar N, Pathak K. Carbon nanotubes in the treatment of skin cancers: Safety and toxic ological aspects. Pharm Nanotechnol. 2017;5(2):95–110. http://doi.org/10.2174/2211738505666170228132148
• 25. Balashanmugam, Sucharithra, Mary A, Selvi T. Efficacy of biopolymeric PVA-AuNPs and PCL-Curcumin loaded electrospun nanofibers and their anticancer activity against A431 skin cancer cell line. Mater Today Commun . 2020;25(101276):101276. https://doi.org/10.1016/j.mtcomm.2020.101276
• 26. Jiang Y, Jiang Z, Ma L, Huang Q. Advances in nanodelivery of green tea catechins to enhance the anticancer activity. Molecules. 2021 ;26(11):3301. https://doi.org/10.3390/molecules26113301
• 27. Wang Y, Zeng L, Song W, Liu J. Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress. Drug Deliv Transl Res. 2021;12(1):15–26. http://.doi.org/10.1007/s13346-021-00898-6
• 28. Song D, Tao W, Tang Z, Hu X. Conductive electronic skin coupled with iontophoresis for sensitive skin treatment. J Drug Deliv Sci Technol. 2024;95(105650):105650. https://doi.org/10.1016/j.jddst.2024.105650
• 29. Petrilli R, Eloy JO, Saggioro FP, Chesca DL, de Souza MC, Dias MVS, et al. Skin cancer treatment effectiveness is improved by iontophoresis of EGFR-targeted liposomes containing 5-FU compared with subcutaneous injection. J Control Release. 2018;283:151–62. http://doi.org/10.1016/j.jconrel.2018.05.038
• 30. Luxenberg MN, Guthrie TH Jr. Chemotherapy of basal cell and squamous cell carcinoma of the eyelids and periorbital tissues. Ophthalmology. 1986;93(4):504–10. http://.doi.org/10.1016/s0161-6420(86)33708-4
• 31. Helmy AM. Overview of recent advancements in the iontophoretic drug delivery to various tissues and organs. J Drug Deliv Sci Technol. 2021;61:102332. https://doi.org/10.1016/j.jddst.2021.102332
• 32. Souto EB, da Ana R, Vieira V, Fangueiro JF, Dias-Ferreira J, Cano A, et al. Non-melanoma skin cancers: physio-pathology and role of lipid delivery systems in new chemotherapeutic treatments. Neoplasia. 2022;30:100810. http://doi.org/10.1016/j.neo.2022.100810
• 33. Park D, Won J, Lee G, Lee Y, Kim C-W, Seo J. Sonophoresis with ultrasound‐responsive liquid‐core nuclei for transdermal drug delivery. Skin Res Technol. 2022;28(2):291–8. http://doi.org/10.1111/srt.13129
• 34. Ahmed Tawfik M, Eltaweel MM, Farag MM, Shamsel-Din HA, Ibrahim AB. Sonophoresis-assisted transdermal delivery of antimigraine-loaded nanolipomers: Radio-tracking, histopathological assessment and in-vivo biodistribution study. Int J Pharm . 2023;644:123338. http://doi.org/10.1016j.ijpharm.2023.123338
• 35. Sun C, Bu N, Hu X. Recent trends in electronic skin for transdermal drug delivery. Intelligent Pharmacy. 2023;1(4):183–91. https://doi.org/10.1016/j.ipha.2023.08.001
• 36. Campelo SN, Huang P-H, Buie CR, Davalos RV. Recent advancements in electroporation technologies: From bench to clinic. Annu Rev Biomed Eng. 2023;25(1):77–100. https://doi.org/10.1146/annurev-bioeng-110220-023800
• 37. Gagliardi A, Giuliano E, Venkateswararao E, Fresta M, Bulotta S, Awasthi V, et al. Biodegradable polymeric nanoparticles for drug delivery to solid tumors. Front Pharmacol . 2021;12. https://doi.org/10.3389/fphar.2021.601626
• 38. Abu-Huwaij R, Abed M, Hamed R. Innovative transdermal doxorubicin patches prepared using greenly synthesized iron oxide nanoparticles for breast cancer treatment. Mater Technol (UK) . 2024;39(1). https://doi.org/10.1080/10667857.2024.2330278
• 39. Seetharam AA, Choudhry H, Bakhrebah MA, Abdulaal WH, Gupta MS, Rizvi SMD, et al. Microneedles Drug Delivery Systems for Treatment of Cancer: A Recent Update. Pharmaceutics. 2020;12(11):1101. https://doi.org/10.3390/pharmaceutics12111101
• 40. Liu P, Chen G, Zhang J. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules. 2022 ;27(4):1372. https://doi.org/10.3390/molecules27041372
• 41. Raju R, Abuwatfa WH, Pitt WG, Husseini GA. Liposomes for the treatment of brain cancer—A review. Pharmaceuticals (Basel). 2023 ;16(8):1056. https://doi.org/10.3390/ph16081056
• 42. Hirenkumar Gajubhai Patel, Sanjay Kumar Jain, Vijay Nigam. Review of Proliposomal Gel for Transdermal drug delivery system. World Journal of Biology Pharmacy and Health Sciences. 2023 ;14(3):332–40. https://doi.org/10.30574/wjbphs.2023.14.3.0280
• 43. Meng J, Guo F, Xu H, Liang W, Wang C, Yang X-D. Combination therapy using co-encapsulated Resveratrol and paclitaxel in liposomes for drug resistance reversal in breast cancer cells in vivo. Sci Rep. 2016;6(1):22390. https://doi.org/10.1038/srep22390
• 44. Moammeri A, Chegeni MM, Sahrayi H, Ghafelehbashi R, Memarzadeh F, Mansouri A, et al. Current advances in niosomes applications for drug delivery and cancer treatment. Mater Today Bio. 2023;23:100837. https://doi.org/10.1016/j.mtbio.2023.100837
• 45. Karimifard S, Rezaei N, Jamshidifar E, Moradi Falah Langeroodi S, Abdihaji M, Mansouri A, et al. PH-responsive chitosan-adorned niosome nanocarriers for co-delivery of drugs for breast cancer therapy. ACS Appl Nano Mater. 2022;5(7):8811–25. https://doi.org/10.1021/acsanm.2c00861
• 46. Ahmadi S, Iman Akbarzadeh, Mohsen Chiani, Seraj M, Far BF. An Optimized and Well-Characterized Niosome-Based Nanocarrier for Letrozole: A Brand- New Hybrid Therapy for Breast Cancer. 2021. https://doi.org/10.21203/rs.3.rs-1197164/v1
• 47. Liga S, Paul C, Moacă E-A, Péter F. Niosomes: Composition, formulation techniques, and recent progress as delivery systems in cancer therapy. Pharmaceutics;16(2):223. https://doi.org/10.3390/pharmaceutics16020223
• 48. Kaveh Zenjanab M, Abdolahinia ED, Alizadeh E, Hamishehkar H, Shahbazi R, Ranjbar-Navazi Z, et al. Hyaluronic acid-targeted niosomes for effective breast cancer chemostarvation therapy. ACS Omega. 2024;9(9):10875–85. https://doi.org/10.1021/acsomega.3c09782
• 49. Kumbhar PS, Kamble V, Vishwas S, Kumbhar P, Kolekar K, Gupta G, et al. Unravelling the success of transferosomes against skin cancer: Journey so far and road ahead. Drug Deliv Transl Res. 2024;14(9):2325–44. https://dx.doi.org/10.1007/s13346-024-01607-9
• 50. Parisa Golestani. Lipid-based nanoparticles as a promising treatment for the skin cancer. Heliyon . 2024;10(9): e29898–8. https://doi.org/10.1016/j.heliyon.2024.e29898
• 51. Shamim MA, Shahid A, Sardar PK, Yeung S, Reyes J, Kim J, et al. Transfersome encapsulated with the R-carvedilol enantiomer for skin cancer chemoprevention. Nanomaterials (Basel).2023;13(5):929. https://doi.org/10.3390/nano13050929
• 52. Khan MA, Pandit J, Sultana Y, Sultana S, Ali A, Aqil M, et al. Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study. Drug Deliv. 2014;22(6):795–802. https://doi.org/10.3109/10717544.2014.902146
• 53. Vishwakarma M, Haider T, Soni V. Next-generation skin cancer treatment: A quality by design perspective on artificial neural network-optimized cationic ethosomes with bleomycin sulphate. J Drug Deliv Sci Technol. 2024;96:105705. https://doi.org/10.1016/j.jddst.2024.105705
• 54. Grossi LN, Braz WR, da Silva NP, Cazarim ELCC, Palmieri MGS, Tavares GD, et al. Ethosomes as delivery system for treatment of melanoma: a mini-review.Oncologie (Paris) . 2023;25(5):455–9. https://doi.org/10.1515/oncologie-2023-0177
• 55. Apolinário AC, Salata GC, de Souza MM, Chorilli M, Lopes LB. Rethinking breast cancer chemoprevention: Technological advantages and enhanced performance of a nanoethosomal-based hydrogel for topical administration of fenretinide. AAPS PharmSciTech . 2022;23(4). https://doi.org/10.1208/s12249-022-02257-1
• 56. Raj A, Dua K, Nair RS, Sarath Chandran C, Alex AT. Transethosome: An ultra-deformable ethanolic vesicle for enhanced transdermal drug delivery. Chem Phys Lipids. 2023;255(105315):105315. https://doi.org/10.1016/j.chemphyslip.2023.105315
• 57. Iqbal S, Zaman M, Waqar MA, Sarwar HS, Jamshaid M. Vesicular approach of cubosomes, its components, preparation techniques, evaluation and their appraisal for targeting cancer cells. J Liposome Res. 2024;34(2):368–84. https://doi.org/10.1080/08982104.2023.2272643
• 58. Gowda BHJ, Ahmed MG, Alshehri SA, Wahab S, Vora LK, Singh Thakur RR, et al. The cubosome-based nanoplatforms in cancer therapy: Seeking new paradigms for cancer theranostics. Environ Res. 2023;237:116894. https://doi.org/10.1016/j.envres.2023.116894
• 59. Sivadasan D, Ramakrishnan K, Mahendran J, Ranganathan H, Karuppaiah A, Rahman H. Solid lipid nanoparticles: Applications and prospects in cancer treatment. Int J Mol Sci .2023;24(7):6199. https://doi.org/10.3390/ijms24076199
• 60. Elkomy MH, Elmowafy M, Shalaby K, Azmy AF, Ahmad N, Zafar A, et al. Development and machine-learning optimization of mucoadhesive nanostructured lipid carriers loaded with fluconazole for treatment of oral candidiasis. Drug Dev Ind Pharm. 2021;47(2):246–58. https://doi.org/10.1080/03639045.2020.1871005
• 61. Thuy LT, Kang N, Choi M, Lee M, Choi JS. Dendrimeric micelles composed of polyamidoamine dendrimer-peptide-cholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection. J Ind Eng Chem. 2022;114:361–76. https://doi.org/10.1016/j.jiec.2022.07.026
• 62. Khan NH, Mir M, Qian L, Baloch M, Ali Khan MF, Rehman A-U-, et al. Skin cancer biology and barriers to treatment: Recent applications of polymeric micro/nanostructures. J Adv Res. 2022;36:223–47. https://doi.org/10.1016/j.jare.2021.06.014
• 63. Crintea A, Motofelea AC, Șovrea AS, Constantin AM, Crivii CB, Carpa R, et al. Dendrimers: Advancements and Potential Applications in Cancer Diagnosis and Treatment—An Overview. Pharmaceutics. 2023;15(5):1406. https://doi.org/10.3390/pharmaceutics15051406
• 64. Karagianni A, Tsierkezos NG, Prato M, Terrones M, Kordatos KV. Application of carbon-based quantum dots in photodynamic therapy. Carbon N Y . 2023;203:273–310. https://doi.org/10.1016/j.carbon.2022.11.026
• 65. Badea MA, Balas M, Ionita D, Dinischiotu A. Carbon nanotubes conjugated with cisplatin activate different apoptosis signaling pathways in 2D and 3D-spheroid triple-negative breast cancer cell cultures: a comparative study. Arch Toxicol. 2024;98(9):2843–66. https://doi.org/10.1007/s00204-024-03779-2
• 66. Zhang Y, Bai Y, Yan B. Functionalized carbon nanotubes for potential medicinal applications. Drug Discov Today. 2010;15(11–12):428–35. https://doi.org/10.1016/j.drudis.2010.04.005
• 67. Kargar B, Fazeli M, Sobhani Z, Hosseinzadeh S, Solhjoo A, Akbarizadeh AR. Exploration of the photothermal role of curcumin-loaded targeted carbon nanotubes as a potential therapy for melanoma cancer. Sci Rep .2024;14(1):1–16. https://doi.org/10.1038/s4598-024-57612-y
• 68. Osmani RAM, Aloorkar NH, Ingale DJ, Kulkarni PK, Hani U, Bhosale RR, et al. Microsponges based novel drug delivery system for augmented arthritis therapy. Saudi Pharm J. 2015;23(5):562–72. https://doi.org/10.1016/j.jsps.2015.02.020
• 69. Kshirsagar SM, Viswaroopan N, Ghosh M, Junaid MSA, Haque S, Khan J, et al. Development of 4-phenylbutyric acid microsponge gel formulations for the treatment of lewisite-mediated skin injury. Drug Deliv Transl Res. 2025;15(2):638–54. https://doi.org/10.1007/s13346-024-01620-y
• 70. Jain SK, Kaur M, Kalyani P, Mehra A, Kaur N, Panchal N. Microsponges enriched gel for enhanced topical delivery of 5-fluorouracil. J Microencapsul. 2019;36(7):677–91. https://doi.org/10.1080/02652048.2019.1667447
• 71. Kumar L, Verma S, Joshi K, Utreja P, Sharma S. Nanofiber as a novel vehicle for transdermal delivery of therapeutic agents: challenges and opportunities. Futur J Pharm Sci . 2021;7(1). https://doi.org/10.1186/s43094-021-00324-1
• 72. Maleki H, Doostan M, Shojaei S, Doostan M, Stamatis H, Gkantzou E, et al. Nanofiber-based systems against skin cancers: Therapeutic and protective approaches. J Drug Deliv Sci Technol. 2023;82:104367. https://doi.org/10.1016/j.ddst.2023.104367
• 73. Khuanekkaphan M, Netsomboon K, Fristiohady A, Asasutjarit R. Development of quercetin solid dispersion-loaded dissolving microneedles and in vitro investigation of their anti-melanoma activities. Pharmaceutics .2024;16(10):1276. https://doi.org/10.3390/pharmaceutics16101276
• 74. Mangla B, Mittal P, Kumar P, Javed S, Ahsan W, Aggarwal G. Development of erlotinib-loaded nanotransferosomal gel for the topical treatment of ductal carcinoma in situ. Nanomedicine (Lond). 2024;19(10):855–74. https://doi.org/10.2217/nnm-2023-0260
• 75. Alabrahim OAA, Azzazy HME-S. Synergistic anticancer effect of Pistacia lentiscus essential oils and 5-Fluorouracil co-loaded onto biodegradable nanofibers against melanoma and breast cancer. Discov Nano. 2024;19(1):27. https://doi.org/10.1186/s11671-024-03962-5
• 76. Yasmeen, Khan MA, Iqbal Z, Aqil M. Carbopol 934-based transethosomal gel of Glycyrrhizic acid for the management of skin cancer. J Drug Deliv Sci Technol. 2024;97(105825):105825. https://doi.org/10.1016/j.jddst.2024.105825
• 77. Yasmeen, Iqubal MK, Sartaj A, Khan MA, Ali J, Baboota S. Topical delivery of Mannose Conjugated-Doxorubicin-Berberine nanostructured lipid carrier gel for skin cancer amelioration: Formulation optimization, in-silico, in-vitro, ex-vivo assessment, and dermatokinetic analysis. J Drug Deliv Sci Technol. 2024;93:105378. https://doi.org/10.1016/j.jddst.2024.105378
• 78. Alam P, Imran M, Gupta DK, Akhtar A. Formulation of transliposomal nanocarrier gel containing strychnine for the effective management of skin cancer. Gels .2023 ;9(10):831. https://doi.org/10.3390/gels9100831
• 79. Gaikwad DS, Chougale RD, Patil KS, Disouza JI, Hajare AA. Design, development, and evaluation of docetaxel-loaded niosomes for the treatment of breast cancer. Futur J Pharm Sci . 2023;9(1). https://doi.org/10.1186/s43094-023-00494-0
• 80. Gadag S, Narayan R, Nayak Y, Garg S, Nayak UY. Design, development and evaluation of Resveratrol transdermal patches for breast cancer therapy. Int J Pharm. 2023;632:122558.https://doi.org/10.1016/j.ijpharm.2022.122558
• 81. Sheikh A, Abourehab MAS, Tulbah AS, Kesharwani P. Aptamer-grafted, cell membrane-coated dendrimer loaded with doxorubicin as a targeted nanosystem against epithelial cellular adhesion molecule (EpCAM) for triple negative breast cancer therapy. J Drug Deliv Sci Technol. 2023;86:104745. https://doi.org/10.1016/j.jddst.2023.104745
• 82. Beal R. Method of administration and treatment. US Patent. 11744853, 2023.
• 83. Perricone NV. Methods and systems for treating or preventing cancer. US Patent. 10155048, 2018
• 84. Stinchcomb AL, Banks SL, Golinski MJ, Howard JL, Hammell DC. Use of cannabidiol prodrugs in topical and transdermal administration with microneedles. US Patent. 9533942, 2017.
• 85. Perricone NV. Cancer treatments and compositions for use thereof. US Patent. 9795632, 2017.
• 86. Mangalathillam S, Rejinold NS, Nair A, Lakshmanan V-K, Nair SV, Jayakumar R. Curcumin loaded chitin nanogels for skin cancer treatment via the transdermal route. Nanoscale. 2012 ;4(1):239–50. https://doi.org/10.1039/c1nr11271f
• 87. Gandhi S, Roy I. Lipid-based inhalable micro- and nanocarriers of active agents for treating non-small-cell lung cancer. Pharmaceutics. 2023 ;15(5):1457. https://doi.org/10.3390/pharmaceutics15051457
• 88. Mukherjee O, Rakshit S, Shanmugam G, Sarkar K. Role of chemotherapeutic drugs in immunomodulation of cancer. Curr Res Immunol. 2023;4:100068. https://doi.org/10.1016/j.crimmu.2023.100068
• 89. Jiang T, Wang T, Li T, Ma Y, Shen S, He B, et al. Enhanced transdermal drug delivery by transfersome-embedded oligopeptide hydrogel for topical chemotherapy of melanoma. ACS Nano. 2018;12(10):9693–701. https://doi.org/10.1021/acsnano.8b03800
• 90. Dilliard SA, Siegwart DJ. Passive, active and endogenous organ-targeted lipid and polymer nanoparticles for delivery of genetic drugs. Nat Rev Mater. 2023 ;8(4):282–300. https://doi.org/10.1038/s41578-022-00529-7
• 91. Almousallam M, Moia C, Zhu H. Development of nanostructured lipid carrier for dacarbazine delivery. Int Nano Lett. 2015;5(4):241–8. https://doi.org/10.1007/s40089-015-0161-8
• 92. Liu J, Wang Z, Zhao S, Ding B. Multifunctional nucleic acid nanostructures for gene therapies. Nano Res. 2018;11(10):5017–27. https://doi.org/10.1007/s12274-018-2093-x
• 93. Chen X. Current and future technological advances in transdermal gene delivery. Adv Drug Deliv Rev. 2017;127:85–105. https://.doi.org/10.1016/j.addr.2017.12.014
• 94. Pan J, Ruan W, Qin M, Long Y, Wan T, Yu K, et al. Intradermal delivery of STAT3 siRNA to treat melanoma via dissolving microneedles. Sci Rep. 2018;8(1):1117. https://doi.org/10.1038/s41598-018-19463-2
• 95. Ma J, Tai Z, Li Y, Li Y, Wang J, Zhou T, et al. Dissolving microneedle-based cascade-activation nanoplatform for enhanced photodynamic therapy of skin cancer. Int J Nanomedicine. 2024;19:2057–70. https://doi.org/10.2147/ijn.s443835
• 96. Inbaraj BS, Lai Y-W, Chen B-H. A comparative study on inhibition of lung cancer cells by nanoemulsion, nanoliposome, nanogold and their folic acid conjugates prepared with collagen peptides from Taiwan tilapia skin. Int J Biol Macromol . 2024;261:129722. https://doi.org/10.1016/j.ijbiomac.2024.129722
• 97. Janani I, Lakra R, Kiran MS, Korrapati PS. Selectivity and sensitivity of molybdenum oxide-polycaprolactone nanofiber composites on skin cancer: Preliminary in-vitro and in-vivo implications. J Trace Elem Med Biol. 2018;49:60–71. http://doi.org/10.1016/j.jtemb.2018.04.033
• 98. Al-Obaidy R, Haider AJ, Al-Musawi S, Arsad N. Targeted delivery of paclitaxel drug using polymer-coated magnetic nanoparticles for fibrosarcoma therapy: in vitro and in vivo studies. Sci Rep. 2023;13(1):1–24.https://doi.org/10.1038/s41598-023-30221-x