BEYOND NEEDLES: INNOVATIONS IN TRANSDERMAL ANTIBIOTIC DELIVERY SYSTEMS

RAWAND M. DAGHMASH; SHEREEN M. ASSAF

doi:10.22159/ijap.2025v17i4.54157

Authors

RAWAND M. DAGHMASH Faculty of Pharmacy, Middle East University, Amman, Jordan https://orcid.org/0009-0006-1822-8443
SHEREEN M. ASSAF Jordan University of Science and Technology, Irbid, Jordan https://orcid.org/0000-0002-3888-9330

DOI:

https://doi.org/10.22159/ijap.2025v17i4.54157

Keywords:

Transdermal antibiotics, Transdermal drug delivery system advantages, Limitations, Microneedles, Characterization

Abstract

As a substitution to traditional needle injections, other non-invasive treatments have lately evolved. Transdermal Drug Delivery Systems (TDDS) are the most appealing of these methods due to their low rejection rate, exceptional simplicity of application, and superior efficiency and endurance among patients. Because this strategy primarily includes local administration, it can could minimize local drug concentration accumulation and broad-spectrum drug distribution to tissues not specifically targeted by the medication. Furthermore, the physicochemical features of the skin translate to several hurdles and limitations in transdermal distribution, necessitating various studies to address these bottlenecks. In this study, we explain the many types of accessible TDDS approaches for delivering antibiotics, as well as a critical evaluation of each method's individual merits and limitations, characterization methodologies, and potential. Advancements in research on these alternative technologies are mentioned in this review.

References

Jeong JH, Lee CY, Chung DK. Probiotic lactic acid bacteria and skin health. Crit Rev Food Sci Nutr. 2016;56(14):2331-7. doi: 10.1080/10408398.2013.834874, PMID 26287529.

Ghanem AM. A review on recent advances in transdermal drug delivery systems of tamsulosin. Int J App Pharm. 2024;16(2):28-33. doi: 10.22159/ijap.2024v16i2.49950.

Alonso C, Carrer V, Espinosa S, Zanuy M, Cordoba M, Vidal B. Prediction of the skin permeability of topical drugs using in silico and in vitro models. Eur J Pharm Sci. 2019 Aug 1;136:104945. doi: 10.1016/j.ejps.2019.05.023, PMID 31163216.

Schaefer H, Redelmeier TE. Skin barrier. Karger Publishers; 1996.

Barry BW. Dermatological formulations; 1983. p. 127-233.

Lu GW, Flynn GL. Cutaneous and transdermal delivery processes and systems of delivery. In: Modern Pharmaceutics. Vol. 2. CRC Press; 2016. p. 61-118.

Smith EW, Maibach HI. Percutaneous penetration enhancers. CRC Press; 1995.

Das PS, Saha P. Design and characterisation of transdermal patches of phenformin hydrochloride. Int J Curr Pharm Sci. 2017;9(6):90-3. doi: 10.22159/ijcpr.2017v9i6.23437.

Anwar N, Jan SU, Gul R. Formulation and evaluation of glibenclamide gel for transdermal drug delivery. Int J Curr Pharm Sci. 2020;12(5):35-9. doi: 10.22159/ijcpr.2020v12i5.39762.

Schaefer H. Skin permeability. Springer Science+Business Media; 2013.

Wysocki AB. Skin anatomy physiology and pathophysiology. Nurs Clin North Am. 1999;34(4):777-97. doi: 10.1016/S0029-6465(22)02423-9, PMID 10523436.

Schaefer H, Redelmeier TE, Lademann J. Skin penetration. In: Johansen JD, Frosch PJ, Lepoittevin JP, editors. Contact dermatitis. Springer; 2011. p. 215-27. doi: 10.1007/978-3-642-03827-3_12.

Fenner J, Clark RS. Anatomy physiology histology and immunohistochemistry of human skin. In: Skin Tissue Engineering and Regenerative Medicine; 2016. p. 1-17. doi: 10.1016/B978-0-12-801654-1.00001-2.

Hadgraft J. Skin the final frontier. Int J Pharm. 2001;224(1-2):1-18. doi: 10.1016/s0378-5173(01)00731-1, PMID 11512545.

Downing DT, Stewart ME, Wertz PW, Colton SW, Abraham W, Strauss JS. Skin lipids: an update. J Invest Dermatol. 1987;88(3) Suppl:2s-6s. doi: 10.1111/1523-1747.ep12468850, PMID 2950180.

Bouwstra J, Pilgram G, Gooris G, Koerten H, Ponec M. New aspects of the skin barrier organization. Skin Pharmacol Appl Skin Physiol. 2001;14 Suppl 1:52-62. doi: 10.1159/000056391, PMID 11509908.

Goldsmith LA. Biochemistry and physiology of the skin. Oxford University Press; 1991.

Reddy G. Review on transdermal drug delivery system. International Journal of Pharmaceutics and Drug Analysis. 2021;9(4):236-40. doi: 10.47957/ijpda.v9i4.482.

Antunes AF, Pereira P, Reis C, Rijo P, Reis C. Nanosystems for skin delivery: from drugs to cosmetics. Curr Drug Metab. 2017;18(5):412-25. doi: 10.2174/1389200218666170306103101, PMID 28266273.

Li J, Xu W, Liang Y, Wang H. The application of skin metabolomics in the context of transdermal drug delivery. Pharmacol Rep. 2017;69(2):252-9. doi: 10.1016/j.pharep.2016.10.011, PMID 28126641.

Manconi M, Caddeo C, Sinico C, Valenti D, Mostallino MC, Lampis S. Penetration enhancer containing vesicles: composition dependence of structural features and skin penetration ability. Eur J Pharm Biopharm. 2012;82(2):352-9. doi: 10.1016/j.ejpb.2012.06.015, PMID 22922162.

Bouwstra JA, Honeywell Nguyen PL. Skin structure and mode of action of vesicles. Adv Drug Deliv Rev. 2002;54 Suppl 1:S41-55. doi: 10.1016/s0169-409x(02)00114-x, PMID 12460715.

Jepps OG, Dancik Y, Anissimov YG, Roberts MS. Modeling the human skin barrier towards a better understanding of dermal absorption. Adv Drug Deliv Rev. 2013;65(2):152-68. doi: 10.1016/j.addr.2012.04.003, PMID 22525516.

Alkilani AZ, McCrudden MT, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics. 2015;7(4):438-70. doi: 10.3390/pharmaceutics7040438, PMID 26506371.

Yusuf NA, Abdassah M, Mauludin R, Chaerunisaa AY. Glibenclamide transethosome patch for transdermal delivery: formulation and evaluations. Int J App Pharm. 2023;15(5):303-9. doi: 10.22159/ijap.2023v15i5.48455.

Kazi KM, Mandal AS, Biswas N, Guha A, Chatterjee S, Behera M. Niosome: a future of targeted drug delivery systems. J Adv Pharm Technol Res. 2010;1(4):374-80. doi: 10.4103/0110-5558.76435, PMID 22247876.

Negut I, Grumezescu V, Grumezescu AM. Treatment strategies for infected wounds. Molecules. 2018;23(9):2392. doi: 10.3390/molecules23092392, PMID 30231567.

O Neill J. Review on antimicrobial resistance: tackling a global health crisis; 2015.

Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic resistant pathogens. Science. 2016;352(6285):535-8. doi: 10.1126/science.aad9382, PMID 27126035.

Lawley TD, Walker AW. Intestinal colonization resistance. Immunology. 2013;138(1):1-11. doi: 10.1111/j.1365-2567.2012.03616.x, PMID 23240815.

Marchesi JR, Adams DH, Fava F, Hermes GD, Hirschfield GM, Hold G. The gut microbiota and host health: a new clinical frontier. Gut. 2016;65(2):330-9. doi: 10.1136/gutjnl-2015-309990, PMID 26338727.

Becattini S, Taur Y, Pamer EG. Antibiotic induced changes in the intestinal microbiota and disease. Trends Mol Med. 2016;22(6):458-78. doi: 10.1016/j.molmed.2016.04.003, PMID 27178527.

Francino MP. Antibiotics and the human gut microbiome: dysbioses and accumulation of resistances. Front Microbiol. 2016 Jan 12;6:1543. doi: 10.3389/fmicb.2015.01543, PMID 26793178.

Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota as revealed by deep 16S rRNA sequencing. PLOS Biol. 2008;6(11):e280. doi: 10.1371/journal.pbio.0060280, PMID 19018661.

Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proc Natl Acad Sci USA. 2011;108 Suppl 1:4554-61. doi: 10.1073/pnas.1000087107, PMID 20847294.

Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A. Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to clostridium difficile induced colitis. Infect Immun. 2012;80(1):62-73. doi: 10.1128/IAI.05496-11, PMID 22006564.

Ubeda C, Taur Y, Jenq RR, Equinda MJ, Son T, Samstein M. Vancomycin resistant enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J Clin Invest. 2010;120(12):4332-41. doi: 10.1172/JCI43918, PMID 21099116.

Madan JC, Salari RC, Saxena D, Davidson L, O Toole GA, Moore JH. Gut microbial colonisation in premature neonates predicts neonatal sepsis. Arch Dis Child Fetal Neonatal Ed. 2012;97(6):F456-62. doi: 10.1136/fetalneonatal-2011-301373, PMID 22562869.

Mai V, Torrazza RM, Ukhanova M, Wang X, Sun Y, Li N. Distortions in development of intestinal microbiota associated with late onset sepsis in preterm infants. PLOS One. 2013;8(1):e52876. doi: 10.1371/journal.pone.0052876, PMID 23341915.

Lu J, Claud EC. Connection between gut microbiome and brain development in preterm infants. Dev Psychobiol. 2019;61(5):739-51. doi: 10.1002/dev.21806, PMID 30460694.

Milliken S, Allen RM, Lamont RF. The role of antimicrobial treatment during pregnancy on the neonatal gut microbiome and the development of atopy asthma allergy and obesity in childhood. Expert Opin Drug Saf. 2019;18(3):173-85. doi: 10.1080/14740338.2019.1579795, PMID 30739516.

Forslund K, Sunagawa S, Kultima JR, Mende DR, Arumugam M, Typas A. Country specific antibiotic use practices impact the human gut resistome. Genome Res. 2013;23(7):1163-9. doi: 10.1101/gr.155465.113, PMID 23568836.

Rolain JM. Food and human gut as reservoirs of transferable antibiotic resistance encoding genes. Front Microbiol. 2013 Jun 24;4:173. doi: 10.3389/fmicb.2013.00173, PMID 23805136.

Bengtsson Palme J, Angelin M, Huss M, Kjellqvist S, Kristiansson E, Palmgren H. The human gut microbiome as a transporter of antibiotic resistance genes between continents. Antimicrob Agents Chemother. 2015;59(10):6551-60. doi: 10.1128/AAC.00933-15, PMID 26259788.

Hu Y, Yang X, Qin J, Lu N, Cheng G, Wu N. Metagenome wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nat Commun. 2013;4(1):2151. doi: 10.1038/ncomms3151, PMID 23877117.

Zhang L, Huang Y, Zhou Y, Buckley T, Wang HH. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota. Antimicrob Agents Chemother. 2013;57(8):3659-66. doi: 10.1128/AAC.00670-13, PMID 23689712.

Nainu F, Permana AD, Djide NJ, Anjani QK, Utami RN, Rumata NR. Pharmaceutical approaches on antimicrobial resistance: prospects and challenges. Antibiotics (Basel). 2021;10(8):981. doi: 10.3390/antibiotics10080981, PMID 34439031.

Saso A, Kampmann B. Vaccine responses in newborns. Semin Immunopathology. 2017 Nov;39(6):627-42. doi: 10.1007/s00281-017-0654-9, PMID 29124321.

Sullivan JV, Myers S. Skin structure and function wound healing and scarring. In: plastic surgery principles and practice. Elsevier; 2022. p. 1-14. doi: 10.1016/B978-0-323-65381-7.00001-0.

Akhtar N, Singh V, Yusuf M, Khan RA. Non-invasive drug delivery technology: development and current status of transdermal drug delivery devices techniques and biomedical applications. Biomed Tech (Berl). 2020;65(3):243-72. doi: 10.1515/bmt-2019-0019, PMID 31926064.

Pires LR, Vinayakumar KB, Turos M, Miguel V, Gaspar J. A perspective on microneedle based drug delivery and diagnostics in paediatrics. J Pers Med. 2019;9(4):49. doi: 10.3390/jpm9040049, PMID 31731656.

Ruby PK, Pathak SM, Aggarwal D. Critical attributes of transdermal drug delivery system (TDDS) a generic product development review. Drug Dev Ind Pharm. 2014;40(11):1421-8. doi: 10.3109/03639045.2013.879720, PMID 24467407.

Mohammed MI, Makky AM, Teaima MH, Abdellatif MM, Hamzawy MA, Khalil MA. Transdermal delivery of vancomycin hydrochloride using combination of nano-ethosomes and iontophoresis: in vitro and in vivo study. Drug Deliv. 2016;23(5):1558-64. doi: 10.3109/10717544.2015.1013200, PMID 25726990.

Hussain A, Altamimi MA, Alshehri S, Imam SS, Shakeel F, Singh SK. Novel approach for transdermal delivery of rifampicin to induce synergistic antimycobacterial effects against cutaneous and systemic tuberculosis using a cationic nanoemulsion gel. Int J Nanomedicine. 2020 Feb 14;15:1073-94. doi: 10.2147/IJN.S236277, PMID 32103956.

Abdellatif AA, Tawfeek HM. Transfersomal nanoparticles for enhanced transdermal delivery of clindamycin. AAPS PharmSciTech. 2016;17(5):1067-74. doi: 10.1208/s12249-015-0441-7, PMID 26511937.

Tanwar H, Sachdeva R. Transdermal drug delivery system: a review. Int J Pharm Sci. 2016;7(6):2274. doi: 10.13040/IJPSR.0975-8232.7(6).2274-90.

Hadgraft J, Lane ME. Passive transdermal drug delivery systems. American Journal of Drug Delivery. 2006;4(3):153-60. doi: 10.2165/00137696-200604030-00003.

Das A, Ahmed AB. Natural permeation enhancer for transdermal drug delivery system and permeation evaluation: a review. Asian J Pharm Clin Res. 2017;10(9):5-9. doi: 10.22159/ajpcr.2017.v10i9.19389.

Bos JD, Meinardi MM. The 500 dalton rule for the skin penetration of chemical compounds and drugs. Exp Dermatol. 2000;9(3):165-9. doi: 10.1034/j.1600-0625.2000.009003165.x, PMID 10839713.

Thong HY, Zhai H, Maibach HI. Percutaneous penetration enhancers: an overview. Skin Pharmacol Physiol. 2007;20(6):272-82. doi: 10.1159/000107575, PMID 17717423.

Michaels AS, Chandrasekaran SK, Shaw JE. Drug permeation through human skin: theory and in vitro experimental measurement. AIChE Journal. 1975;21(5):985-96. doi: 10.1002/aic.690210522.

Albery WJ, Hadgraft JJ. Percutaneous absorption: in vivo experiments. J Pharm Pharmacol. 1979;31(3):140-7. doi: 10.1111/j.2042-7158.1979.tb13456.x, PMID 34686.

Tojo K. Random brick model for drug transport across stratum corneum. J Pharm Sci. 1987;76(12):889-91. doi: 10.1002/jps.2600761209, PMID 3440932.

Goffin V, Henry F, Pierard Franchimont C, Pierard GE. Penetration enhancers assessed by corneoxenometry. Skin Pharmacol Appl Skin Physiol. 2000;13(5):280-4. doi: 10.1159/000029934, PMID 10940818.

Barry BW. Lipid protein partitioning theory of skin penetration enhancement. Journal of Controlled Release. 1991;15(3):237-48. doi: 10.1016/0168-3659(91)90115-T.

Karande P, Jain A, Ergun K, Kispersky V, Mitragotri S. Design principles of chemical penetration enhancers for transdermal drug delivery. Proc Natl Acad Sci U S A. 2005;102(13):4688-93. doi: 10.1073/pnas.0501176102, PMID 15774584.

Kogan A, Garti N. Microemulsions as transdermal drug delivery vehicles. Adv Colloid Interface Sci. 2006 Nov 16;123-126:369-85. doi: 10.1016/j.cis.2006.05.014, PMID 16843424.

Karande P, Jain A, Mitragotri S. Discovery of transdermal penetration enhancers by high throughput screening. Nat Biotechnol. 2004;22(2):192-7. doi: 10.1038/nbt928, PMID 14704682.

Hamilton JG. Needle phobia: a neglected diagnosis. J Fam Pract. 1995;41(2):169-75. PMID 7636457.

Sloan KB. Prodrugs: topical and ocular drug delivery. CRC Press; 1st edition. Informa Health Care; 1992:53:336.

Hurkmans JF, Bodde HE, Van Driel LM, Van Doorne H, Junginger HE. Skin irritation caused by transdermal drug delivery systems during long term (5 d) application. Br J Dermatol. 1985;112(4):461-7. doi: 10.1111/j.1365-2133.1985.tb02321.x, PMID 3994921.

Paudel KS, Milewski M, Swadley CL, Brogden NK, Ghosh P, Stinchcomb AL. Challenges and opportunities in dermal/transdermal delivery. Ther Deliv. 2010;1(1):109-31. doi: 10.4155/tde.10.16, PMID 21132122.

Berner B, Wilson DR, Guy RH, Mazzenga GC, Clarke FH, Maibach HI. The relationship of pKa and acute skin irritation in man. Pharm Res. 1988;5(10):660-3. doi: 10.1023/a:1015931105660, PMID 3244620.

Berner B, Wilson DR, Steffens RJ, Mazzenga GC, Hinz R, Guy RH. The relationship between pKa and skin irritation for a series of basic penetrants in man. Fundam Appl Toxicol. 1990;15(4):760-6. doi: 10.1016/0272-0590(90)90192-m, PMID 2086317.

Andersen PH, Nangia A, Bjerring P, Maibach HI. Chemical and pharmacologic skin irritation in man. A reflectance spectroscopic study. Contact Dermatitis. 1991;25(5):283-9. doi: 10.1111/j.1600-0536.1991.tb01875.x, PMID 1809531.

Mangia A, Andersen PH, Berner B, Maibach HI. High dissociation constants (pKa) of basic permeants are associated with in vivo skin irritation in man. Contact Dermatitis. 1996;34(4):237-42. doi: 10.1111/j.1600-0536.1996.tb02192.x.

Schmid Wendtner MH, Korting HC. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol. 2006;19(6):296-302. doi: 10.1159/000094670, PMID 16864974.

Antoine JL, Contreras JL, Van Neste DJ. pH influence of surfactant induced skin irritation a non-invasive multiparametric study with sodium laurylsulfate. Derm Beruf Umwelt. 1989;37(3):96-100. PMID 2743874.

Ananthapadmanabhan KP, Lips A, Vincent C, Meyer F, Caso S, Johnson A. pH-induced alterations in stratum corneum properties. Int J Cosmet Sci. 2003;25(3):103-12. doi: 10.1046/j.1467-2494.2003.00176.x, PMID 18494892.

Williams A. Pharmaceutical solvents as vehicles for topical dosage forms. In: Augustijns P, Brewster ME, editors. Solvent systems and their selection in pharmaceutics and biopharmaceutics. Springer; 2007. p. 403-26. doi: 10.1007/978-0-387-69154-1_13.

Matsumura H, Oka K, Umekage K, Akita H, Kawai J, Kitazawa Y. Effect of occlusion on human skin. Contact Dermatitis. 1995;33(4):231-5. doi: 10.1111/j.1600-0536.1995.tb00472.x, PMID 8654072.

Homick JL, Kohl RL, Reschke MF, Degioanni J, Cintron Trevino NM. Transdermal scopolamine in the prevention of motion sickness: evaluation of the time course of efficacy. Aviat Space Environ Med. 1983;54(11):994-1000. PMID 6651736.

Van Der Valk PG, Maibach HI. Post application occlusion substantially increases the irritant response of the skin to repeated short term sodium lauryl sulfate (SLS) exposure. Contact Dermatitis. 1989;21(5):335-8. doi: 10.1111/j.1600-0536.1989.tb04754.x, PMID 2620512.

Tsai TF, Maibach HI. How irritant is water? An overview. Contact Dermatitis. 1999;41(6):311-4. doi: 10.1111/j.1600-0536.1999.tb06990.x, PMID 10617210.

Dwyer CM, Forsyth AJ. Allergic contact dermatitis from methacrylates in a nicotine transdermal patch. Contact Dermatitis. 1994;30(5):309-10. doi: 10.1111/j.1600-0536.1994.tb00612.x, PMID 8088155.

Ross D, Rees M, Godfree V, Cooper A, Hart D, Kingsland C. Randomised crossover comparison of skin irritation with two transdermal oestradiol patches. BMJ. 1997;315(7103):288. doi: 10.1136/bmj.315.7103.288, PMID 9274549.

Marier JF, Lor M, Potvin D, Dimarco M, Morelli G, Saedder EA. Pharmacokinetics tolerability and performance of a novel matrix transdermal delivery system of fentanyl relative to the commercially available reservoir formulation in healthy subjects. J Clin Pharmacol. 2006;46(6):642-53. doi: 10.1177/0091270006286901, PMID 16707411.

Wester RC, Patel R, Nacht S, Leyden J, Melendres J, Maibach H. Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy. J Am Acad Dermatol. 1991;24(5 Pt 1):720-6. doi: 10.1016/0190-9622(91)70109-f, PMID 1869643.

Sudhakar K, Fuloria S, Subramaniyan V, Sathasivam KV, Azad AK, Swain SS. Ultraflexible liposome nanocargo as a dermal and transdermal drug delivery system. Nanomaterials (Basel). 2021;11(10):2557. doi: 10.3390/nano11102557, PMID 34685005.

Schafer Korting M, Korting HC, Ponce Poschl EJ. Liposomal tretinoin for uncomplicated acne vulgaris. Clin Investig. 1994;72(12):1086-91. doi: 10.1007/BF00577761, PMID 7711421.

Zhai H, Willard P, Maibach HI. Evaluating skin protective materials against contact irritants and allergens an in vivo screening human model. Contact Dermatitis. 1998;38(3):155-8. doi: 10.1111/j.1600-0536.1998.tb05683.x, PMID 9536408.

Wigger Alberti W, Hinnen U, Elsner PJ. Predictive testing of metalworking fluids: a comparison of 2 cumulative human irritation models and correlation with epidemiological data. Contact Dermatitis. 1997;36(1):14-20. doi: 10.1111/j.1600-0536.1997.tb00916.x, PMID 9034682.

Ben Shabat S, Baruch N, Sintov AC. Conjugates of unsaturated fatty acids with propylene glycol as potentially less irritant skin penetration enhancers. Drug Dev Ind Pharm. 2007;33(11):1169-75. doi: 10.1080/03639040701199258, PMID 18058312.

Sintov A, Ben Shabat SJ. Design of fatty acid conjugates for dermal delivery and topical therapeutics. Crit Rev Ther Drug Carrier Syst. 2006;23(1):67-87. doi: 10.1615/critrevtherdrugcarriersyst.v23.i1.20, PMID 16749899.

Karande P, Mitragotri SB. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta. 2009;1788(11):2362-73. doi: 10.1016/j.bbamem.2009.08.015, PMID 19733150.

Wilson DE, Kaidbey K, Boike SC, Jorkasky DK. Use of topical corticosteroid pretreatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal therapy. Clin Ther. 1998;20(2):299-306. doi: 10.1016/s0149-2918(98)80093-3, PMID 9589821.

Amkraut AA, Jordan WP, Taskovich LJ. Effect of coadministration of corticosteroids on the development of contact sensitization. J Am Acad Dermatol. 1996;35(1):27-31. doi: 10.1016/S0190-9622(96)90491-0, PMID 8682959.

Andersen F, Hedegaard K, Petersen TK, Bindslev Jensen C, Fullerton A, Andersen KE. Anti-irritants I: dose response in acute irritation. Contact Dermatitis. 2006;55(3):148-54. doi: 10.1111/j.1600-0536.2006.00752.x, PMID 16918613.

Andersen F, Hedegaard K, Petersen TK, Bindslev Jensen C, Fullerton A, Andersen KE. Comparison of the effect of glycerol and triamcinolone acetonide on cumulative skin irritation in a randomized trial. J Am Acad Dermatol. 2007;56(2):228-35. doi: 10.1016/j.jaad.2006.08.063, PMID 17156893.

Huang YB, Tsai YH, Chang JS, Liu JC, Tsai MJ, Wu PC. Effect of antioxidants and anti-irritants on the stability skin irritation and penetration capacity of captopril gel. Int J Pharm. 2002;241(2):345-51. doi: 10.1016/s0378-5173(02)00265-x, PMID 12100862.

Benson HA, Grice JE, Mohammed Y, Namjoshi S, Roberts MS. Topical and transdermal drug delivery: from simple potions to smart technologies. Curr Drug Deliv. 2019;16(5):444-60. doi: 10.2174/1567201816666190201143457, PMID 30714524.

Ramadon D, McCrudden MT, Courtenay AJ, Donnelly RF. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Deliv Transl Res. 2022;12(4):758-91. doi: 10.1007/s13346-021-00909-6, PMID 33474709.

Bird D, Ravindra NM. Transdermal drug delivery and patches an overview. Med Devices & Sens. 2020;3(6):e10069. doi: 10.1002/mds3.10069.

Dhiman S, Singh TG, Rehni AK. Transdermal patches: a recent approach to new drug delivery system. International Journal of Pharmacy and Pharmaceutical Sciences. 2011;3(5):26-34.

Agrawal S. Microneedles: an advancement to transdermal drug delivery system approach. Journal of Applied Pharmaceutical Science. 2020;10(3):149-59. doi: 10.7324/JAPS.2020.103019.

Zhao Z, Chen Y, Shi Y. Microneedles: a potential strategy in transdermal delivery and application in the management of psoriasis. RSC Adv. 2020;10(24):14040-9. doi: 10.1039/d0ra00735h, PMID 35498446.

Jung JH, Jin SG. Microneedle for transdermal drug delivery: current trends and fabrication. J Pharm Investig. 2021;51(5):503-17. doi: 10.1007/s40005-021-00512-4, PMID 33686358.

Shakya AK, Ingrole RS, Joshi G, Uddin MJ, Anvari S, Davis CM. Microneedles coated with peanut allergen enable desensitization of peanut sensitized mice. J Control Release. 2019 Nov 28;314:38-47. doi: 10.1016/j.jconrel.2019.09.022, PMID 31626861.

Lim J, Tahk D, Yu J, Min DH, Jeon NL. Design rules for a tunable merged-tip microneedle. Microsyst Nanoeng. 2018;4(1):29. doi: 10.1038/s41378-018-0028-z, PMID 31057917.

Dardano P, Calio A, Di Palma V, Bevilacqua MF, Di Matteo A, De Stefano L. A photolithographic approach to polymeric microneedles array fabrication. Materials (Basel). 2015;8(12):8661-73. doi: 10.3390/ma8125484, PMID 28793736.

Han D, Morde RS, Mariani S, La Mattina AA, Vignali E, Yang C. 4D printing of a bioinspired microneedle array with backward facing barbs for enhanced tissue adhesion. Adv Funct Materials. 2020;30(11):1909197. doi: 10.1002/adfm.201909197.

Balmert SC, Carey CD, Falo GD, Sethi SK, Erdos G, Korkmaz E. Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination. J Control Release. 2020 Jan 10;317:336-46. doi: 10.1016/j.jconrel.2019.11.023, PMID 31756393.

Jeong WY, Kwon M, Choi HE, Kim KS. Recent advances in transdermal drug delivery systems: a review. Biomater Res. 2021;25(1):24. doi: 10.1186/s40824-021-00226-6, PMID 34321111.

Kim HM, Lim YY, An JH, Kim MN, Kim BJ. Transdermal drug delivery using disk microneedle rollers in a hairless rat model. Int J Dermatol. 2012;51(7):859-63. doi: 10.1111/j.1365-4632.2011.05343.x, PMID 22715835.

Li K, Yoo KH, Byun HJ, Lim YY, Kim MN, Hong HK. The microneedle roller is an effective device for enhancing transdermal drug delivery. Int J Dermatol. 2012;51(9):1137-9. doi: 10.1111/j.1365-4632.2010.04703.x, PMID 22233171.

Bal SM, Caussin J, Pavel S, Bouwstra JA. In vivo assessment of safety of microneedle arrays in human skin. Eur J Pharm Sci. 2008;35(3):193-202. doi: 10.1016/j.ejps.2008.06.016, PMID 18657610.

Jamaledin R, Yiu CK, Zare EN, Niu LN, Vecchione R, Chen G. Advances in antimicrobial microneedle patches for combating infections. Adv Mater. 2020;32(33):e2002129. doi: 10.1002/adma.202002129, PMID 32602146.

Donnelly RF, Singh TR, Garland MJ, Migalska K, Majithiya R, McCrudden CM. Hydrogel forming microneedle arrays for enhanced transdermal drug delivery. Adv Funct Mater. 2012;22(23):4879-90. doi: 10.1002/adfm.201200864, PMID 23606824.

Donnelly RF, Singh TR, Morrow DI, Woolfson AD. Microneedle mediated transdermal and intradermal drug delivery. Chichester: John Wiley & Sons; 2012. doi: 10.1002/9781119959687.

Donnelly RF, McCrudden MT, Zaid Alkilani A, Larraneta E, McAlister E, Courtenay AJ. Hydrogel forming microneedles prepared from super swelling polymers combined with lyophilised wafers for transdermal drug delivery. PLOS One. 2014;9(10):e111547. doi: 10.1371/journal.pone.0111547, PMID 25360806.

Migdadi EM, Courtenay AJ, Tekko IA, McCrudden MT, Kearney MC, McAlister E. Hydrogel forming microneedles enhance transdermal delivery of metformin hydrochloride. J Control Release. 2018 Sep 10;285:142-51. doi: 10.1016/j.jconrel.2018.07.009, PMID 29990526.

Kearney MC, McKenna PE, Quinn HL, Courtenay AJ, Larraneta E, Donnelly RF. Design and development of liquid drug reservoirs for microneedle delivery of poorly soluble drug molecules. Pharmaceutics. 2019;11(11):605. doi: 10.3390/pharmaceutics11110605, PMID 31766145.

Anjani QK, Permana AD, Carcamo Martinez A, Dominguez Robles J, Tekko IA, Larraneta E. Versatility of hydrogel forming microneedles in in vitro transdermal delivery of tuberculosis drugs. Eur J Pharm Biopharm. 2021 Jan;158:294-312. doi: 10.1016/j.ejpb.2020.12.003, PMID 33309844.

Gonzalez Vazquez P, Larraneta E, McCrudden MT, Jarrahian C, Rein Weston A, Quintanar Solares M. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis. J Control Release. 2017 Nov 10;265:30-40. doi: 10.1016/j.jconrel.2017.07.032, PMID 28754611.

Sabri AH, Anjani QK, Utomo E, Ripolin A, Donnelly RF. Development and characterization of a dry reservoir hydrogel forming microneedles composite for minimally invasive delivery of cefazolin. Int J Pharm. 2022 Apr 5;617:121593. doi: 10.1016/j.ijpharm.2022.121593, PMID 35182702.

Abraham AM, Anjani QK, Adhami M, Hutton AR, Larraneta E, Donnelly RF. Novel smart reservoirs for hydrogel forming microneedles to improve the transdermal delivery of rifampicin. J Mater Chem B. 2024;12(18):4375-88. doi: 10.1039/d4tb00110a, PMID 38477350.

Zhao L, Vora LK, Kelly SA, Li L, Larraneta E, McCarthy HO. Hydrogel forming microarray patch mediated transdermal delivery of tetracycline hydrochloride. J Control Release. 2023 Apr;356:196-204. doi: 10.1016/j.jconrel.2023.02.031, PMID 36868520.

Chandran R, Tohit ER, Stanslas J, Tuan Mahmood TM. Recent advances and challenges in microneedle mediated transdermal protein and peptide drug delivery. In: Biomaterials and bionanotechnology. Elsevier; 2019. p. 495-525. doi: 10.1016/B978-0-12-814427-5.00014-7.

Ryu HR, Jeong HR, Seon Woo HS, Kim JS, Lee SK, Kim HJ. Efficacy of a bleomycin microneedle patch for the treatment of warts. Drug Deliv Transl Res. 2018;8(1):273-80. doi: 10.1007/s13346-017-0458-4, PMID 29204924.

Sanjay ST, Zhou W, Dou M, Tavakoli H, Ma L, Xu F. Recent advances of controlled drug delivery using microfluidic platforms. Adv Drug Deliv Rev. 2018 Mar 15;128:3-28. doi: 10.1016/j.addr.2017.09.013, PMID 28919029.

Bhatnagar S, Dave K, Venuganti VV. Microneedles in the clinic. J Control Release. 2017 Aug 28;260:164-82. doi: 10.1016/j.jconrel.2017.05.029, PMID 28549948.

Yadav V, Sharma PK, Murty US, Mohan NH, Thomas R, Dwivedy SK. 3D printed hollow microneedles array using stereolithography for efficient transdermal delivery of rifampicin. Int J Pharm. 2021 Aug 10;605:120815. doi: 10.1016/j.ijpharm.2021.120815, PMID 34153441.

Hong X, Wei L, Wu F, Wu Z, Chen L, Liu Z. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Devel Ther. 2013 Sep 4;7:945-52. doi: 10.2147/DDDT.S44401, PMID 24039404.

Park JH, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication mechanics and transdermal drug delivery. J Control Release. 2005;104(1):51-66. doi: 10.1016/j.jconrel.2005.02.002, PMID 15866334.

Marin E, Briceno MI, Caballero George CJ. Critical evaluation of biodegradable polymers used in nanodrugs. Int J Nanomedicine. 2013;8:3071-90. doi: 10.2147/IJN.S47186, PMID 23990720.

Zan P, Than A, Duong PK, Song J, Xu C, Chen P. Antimicrobial microneedle patch for treating deep cutaneous fungal infection. Advanced Therapeutics. 2019;2(10):1900064. doi: 10.1002/adtp.201900064.

Tan Y, Wang Y, Zeng N, Zhang Q, Wu M, Wu Y. Degradable microneedle patch loaded with doxycycline hydrochloride and vascular endothelial growth factors for promoting diabetic wound healing. Advanced Therapeutics. 2024;7(2):2300264. doi: 10.1002/adtp.202300264.

Zafar S, Arshad MS, Rana SJ, Patel M, Yousef B, Ahmad Z. Engineering of clarithromycin loaded stimulus responsive dissolving microneedle patches for the treatment of biofilms. Int J Pharm. 2023 Jun 10;640:123003. doi: 10.1016/j.ijpharm.2023.123003, PMID 37146953.

Li X, Du W, Xu W, Ling G, Zhang P. Dissolving microneedles based on ZnO nanoparticles and an ionic liquid as synergistic antibacterial agents. J Mater Chem B. 2023;11(19):4354-64. doi: 10.1039/d3tb00127j, PMID 37159019.

He X, Sun J, Zhuang J, Xu H, Liu Y, Wu D. Microneedle system for transdermal drug and vaccine delivery: devices safety and prospects. Dose Response. 2019;17(4):1559325819878585. doi: 10.1177/1559325819878585, PMID 31662709.

Xie L, Zeng H, Sun J, Qian W. Engineering microneedles for therapy and diagnosis: a survey. Micromachines (Basel). 2020;11(3):271. doi: 10.3390/mi11030271, PMID 32150866.

Lee KJ, Jeong SS, Roh DH, Kim DY, Choi HK, Lee EH. A practical guide to the development of microneedle systems in clinical trials or on the market. Int J Pharm. 2020 Jan 5;573:118778. doi: 10.1016/j.ijpharm.2019.118778, PMID 31678394.

Wei Ze L, Mei Rong H, Jian Ping Z, Yong Qiang Z, Bao Hua H, Ting L. Super short solid silicon microneedles for transdermal drug delivery applications. International Journal of Pharmaceutics. 2010;389(1-2):122-9. doi: 10.1016/j.ijpharm.2010.01.024.

Pradeep Narayanan S, Raghavan SJ. Fabrication and characterization of gold coated solid silicon microneedles with improved biocompatibility. Int J Adv Manuf Technol. 2019;104(9-12):3327-33. doi: 10.1007/s00170-018-2596-3.

Tabassum N, Rudd D, Yan L, Voelcker NH, Alba M. Porous silicon microneedle patches for delivery of polymyxin based antimicrobials. Nano Select. 2024;5(7-8):2300116. doi: 10.1002/nano.202300116.

Dermol Cerne J, Pirc E, Miklavcic D. Mechanistic view of skin electroporation models and dosimetry for successful applications: an expert review. Expert Opin Drug Deliv. 2020;17(5):689-704. doi: 10.1080/17425247.2020.1745772, PMID 32192364.

Lin CH, Aljuffali IA, Fang JY. Lasers as an approach for promoting drug delivery via skin. Expert Opin Drug Deliv. 2014;11(4):599-614. doi: 10.1517/17425247.2014.885501, PMID 24490743.

Park H, Park H, Na K. Dual propionibacterium acnes therapy using skin penetration enhanced liposomes loaded with a photosensitizer and an antibiotic. J Porphyrins Phthalocyanines. 2015;19(8):956-66. doi: 10.1142/S1088424615500686.

Stanekzai A, Sudhakar C, Zhakfar A, Karan VS. Recent approaches in transdermal drug delivery system. Rese Jour of Pharm and Technol. 2019;12(9):4550-8. doi: 10.5958/0974-360X.2019.00783.2.

Gandhi K. Transdermal drug delivery a review. International Journal of Research in Pharmaceutical Sciences. 2012;3(3).

Babaie S, Bakhshayesh AR, Ha JW, Hamishehkar H, Kim KH. Invasome: a novel nanocarrier for transdermal drug delivery. Nanomaterials (Basel). 2020;10(2):341. doi: 10.3390/nano10020341, PMID 32079276.

Palac Z, Engesland A, Flaten GE, Skalko Basnet N, Filipovic Grcic J, Vanic Z. Liposomes for (trans) dermal drug delivery: the skin-PVPA as a novel in vitro stratum corneum model in formulation development. J Liposome Res. 2014;24(4):313-22. doi: 10.3109/08982104.2014.899368, PMID 24646434.

Cevc GJ. Transfersomes liposomes and other lipid suspensions on the skin: permeation enhancement vesicle penetration and transdermal drug delivery. Crit Rev Ther Drug Carrier Syst. 1996;13(3-4):257-388. doi: 10.1615/critrevtherdrugcarriersyst.v13.i3-4.30, PMID 9016383.

Tiwari R. Development characterization and transdermal delivery of dapsone and an antibiotic entrapped in ethanolic liposomal gel for the treatment of lepromatous leprosy. The Open Nanomedicine Journal. 2018 Apr;5:1. doi: 10.2174/1875933501805010001.

Li C, Zhang X, Huang X, Wang X, Liao G, Chen Z. Preparation and characterization of flexible nanoliposomes loaded with daptomycin a novel antibiotic for topical skin therapy. Int J Nanomedicine. 2013 Mar 24;8:1285-92. doi: 10.2147/IJN.S41695, PMID 23569376.

Cai Y, Chu Y, Gong Y, Hong Y, Song F, Wang H. Enhanced transdermal peptide modified flexible liposomes for efficient percutaneous delivery of chrysomycin a to treat subcutaneous melanoma and intradermal MRSA infection. Adv Healthc Mater. 2023;12(26):e2300881. doi: 10.1002/adhm.202300881, PMID 37267625.

Zhang Z, Liu Y, Chen Y, Li L, Lan P, He D. Transdermal delivery of 5-aminolevulinic acid by nanoethosome gels for photodynamic therapy of hypertrophic scars. ACS Appl Mater Interfaces. 2019;11(4):3704-14. doi: 10.1021/acsami.8b17498, PMID 30589527.

Shah PK, Majumdar SJ. Patent review on ethosomes: novel vesicular carrier for enhanced transdermal drug delivery system. Journal of Advanced Pharmacy Education & Research. 2014;4(4):380-7.

Mohammed MI. Formulation and characterization of ethosomes bearing vancomycin hydrochloride for transdermal delivery. Int J Pharm Pharm Sci. 2014;6(11):190-4.

Tiwari R, Tiwari G, Wal P, Wal A, Maurya P. Development characterization and transdermal delivery of dapsone and an antibiotic entrapped in ethanolic liposomal gel for the treatment of lapromatous leprosy. Open Nanomed J. 2018;5(1):1-15. doi: 10.2174/1875933501805010001.

Paolino D, Lucania G, Mardente D, Alhaique F, Fresta M. Ethosomes for skin delivery of ammonium glycyrrhizinate: in vitro percutaneous permeation through human skin and in vivo anti-inflammatory activity on human volunteers. J Control Release. 2005;106(1-2):99-110. doi: 10.1016/j.jconrel.2005.04.007, PMID 15935505.

Lodzki M, Godin B, Rakou L, Mechoulam R, Gallily R, Touitou E. Cannabidiol transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003;93(3):377-87. doi: 10.1016/j.jconrel.2003.09.001, PMID 14644587.

Muller RH, Mader K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm. 2000;50(1):161-77. doi: 10.1016/s0939-6411(00)00087-4, PMID 10840199.

Doktorovova S, Kovacevic AB, Garcia ML, Souto EB. Preclinical safety of solid lipid nanoparticles and nanostructured lipid carriers: current evidence from in vitro and in vivo evaluation. Eur J Pharm Biopharm. 2016;108:235-52. doi: 10.1016/j.ejpb.2016.08.001, PMID 27519829.

Yoon G, Park JW, Yoon IS. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs): recent advances in drug delivery. J Pharm Investig. 2013;43(5):353-62. doi: 10.1007/s40005-013-0087-y.

Makwana V, Jain R, Patel K, Nivsarkar M, Joshi A. Solid lipid nanoparticles (SLN) of efavirenz as lymph targeting drug delivery system: elucidation of mechanism of uptake using chylomicron flow blocking approach. Int J Pharm. 2015;495(1):439-46. doi: 10.1016/j.ijpharm.2015.09.014, PMID 26367780.

Nasrollahzadeh M, Ganji F, Taghizadeh SM, Vasheghani Farahani E, Mohiti Asli M. Drug in adhesive transdermal patch containing antibiotic loaded solid lipid nanoparticles. J Biosci Bioeng. 2022;134(5):471-6. doi: 10.1016/j.jbiosc.2022.08.003, PMID 36151004.

Ghasemiyeh P, Mohammadi Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications advantages and disadvantages. Res Pharm Sci. 2018;13(4):288-303. doi: 10.4103/1735-5362.235156, PMID 30065762.

Beloqui A, Solinis MA, Rodriguez Gascon A, Almeida AJ, Preat V. Nanostructured lipid carriers: promising drug delivery systems for future clinics. Nanomedicine. 2016;12(1):143-61. doi: 10.1016/j.nano.2015.09.004, PMID 26410277.

Shidhaye SS, Vaidya R, Sutar S, Patwardhan A, Kadam VJ. Solid lipid nanoparticles and nanostructured lipid carriers innovative generations of solid lipid carriers. Curr Drug Deliv. 2008;5(4):324-31. doi: 10.2174/156720108785915087, PMID 18855604.

Tariq A, Kazim T, Khan MF, Usman M, Khan A. Reshaping antibiotic delivery: chitosan based polymeric hydrogel for transdermal treatment of drug resistant bacteria. Polym Adv Technol. 2024;35(3):e6331. doi: 10.1002/pat.6331.

Dhal S, Gavara RR, Pal K, Banerjee I, Mishra M, Giri S. Facile transdermal delivery of upconversion nanoparticle by iontophoresis responsive magneto upconversion oleogel. Nano Ex. 2020;1(1):010012. doi: 10.1088/2632-959X/ab81e1.

Lee SY, Kang MS, Jeong WY, Han DW, Kim KS. Hyaluronic acid based theranostic nanomedicines for targeted cancer therapy. Cancers (Basel). 2020;12(4):940. doi: 10.3390/cancers12040940, PMID 32290285.

Jijie R, Barras A, Boukherroub R, Szunerits S. Nanomaterials for transdermal drug delivery: beyond the state of the art of liposomal structures. J Mater Chem B. 2017;5(44):8653-75. doi: 10.1039/c7tb02529g, PMID 32264260.

Jeong WY, Kim S, Lee SY, Lee H, Han DW, Yang SY. Transdermal delivery of minoxidil using HA-PLGA nanoparticles for the treatment in alopecia. Biomater Res. 2019;23(1):16. doi: 10.1186/s40824-019-0164-z, PMID 31695925.

Escobar Chavez JJ, Diaz Torres R, Rodriguez Cruz IM, Domnguez Delgado, Sampere Morales, Angeles Anguiano. Nanocarriers for transdermal drug delivery. RRTD. 2012;1(1):3. doi: 10.2147/RRTD.S32621.

Patra JK, Gitishree Das ON, Fernandes Fraceto L, Ramos Campos EV, Del Pilar Rodriguez Torres M, Acosta Torres LS, Diaz Torres LA. Nano based drug delivery systems: recent developments and prospects. Journal of Nanobiotechnology. 2018;16(71)2-33. doi: 10.1186/s12951-018-0392-8.

Buhecha MD, Lansley AB, Somavarapu S, Pannala AS. Development and characterization of PLA nanoparticles for pulmonary drug delivery: co-encapsulation of theophylline and budesonide a hydrophilic and lipophilic drug. Journal of Drug Delivery Science and Technology. 2019;53:101128. doi: 10.1016/j.jddst.2019.101128.

Mader P, Fliessbach A, Dubois D, Gunst L, Fried P, Niggli U. Soil fertility and biodiversity in organic farming. Science. 2002;296(5573):1694-7. doi: 10.1126/science.1071148, PMID 12040197.

Vargason AM, Anselmo AC, Mitragotri SJ. The evolution of commercial drug delivery technologies. Nat Biomed Eng. 2021;5(9):951-67. doi: 10.1038/s41551-021-00698-w, PMID 33795852.

Chan, BK J Eng SJ Leong. Scaffolding in tissue engineering: general approaches and tissue specific considerations. Eur Spine J. 2008;17(4):467-79. doi: 10.1007/s00586-008-0745-3.

Khajavi R, M Abbasipour, A Bahador. Electrospun biodegradable nanofibers scaffolds bone tissue eng. J Appl Polym Sci. 2016;133(3):42883. doi: 10.1002/app.42883.

Sivan M, Madheswaran D, Valtera J, Kostakova EK, Lukas D. Alternating current electrospinning: the impacts of various high voltage signal shapes and frequencies on the spinnability and productivity of polycaprolactone nanofibers. Materials & Design. 2022;213:110308. doi: 10.1016/j.matdes.2021.110308.

Teraoka I. Polymer solutions: an introduction to physical properties. Chichester: John Wiley & Sons; 2002. doi: 10.1002/0471224510.

Reneker DH, Chun IJ. Nanometre diameter fibres of polymer produced by electrospinning. Nanotechnology. 1996;7(3):216. doi: 10.1088/0957-4484/7/3/009.

Li D, Babel A, Jenekhe S, Xia Y. Nanofibers of conjugated polymers prepared by electrospinning with a two capillary spinneret. Advanced Materials. 2004;16(22):2062-6. doi: 10.1002/adma.200400606.

Soltani I, Macosko CW. Influence of rheology and surface properties on morphology of nanofibers derived from islands in the sea meltblown nonwovens. Polymer. 2018 Jun 6;145:21-30. doi: 10.1016/j.polymer.2018.04.051.

Zhang Y, Lim CT, Ramakrishna S, Huang ZM. Recent development of polymer nanofibers for biomedical and biotechnological applications. J Mater Sci Mater Med. 2005;16(10):933-46. doi: 10.1007/s10856-005-4428-x, PMID 16167102.

Bockelmann J, Klinkhammer K, Von Holst A, Seiler N, Faissner A, Brook GA. Functionalization of electrospun poly(ε-caprolactone) fibers with the extracellular matrix derived peptide GRGDS improves guidance of schwann cell migration and axonal growth. Tissue Eng Part A. 2011;17(3-4):475-86. doi: 10.1089/ten.TEA.2010.0369, PMID 20819000.

Gerardo Nava J, Fuhrmann T, Klinkhammer K, Seiler N, Mey J, Klee D. Human neural cell interactions with orientated electrospun nanofibers in vitro. Nanomedicine (Lond). 2009;4(1):11-30. doi: 10.2217/17435889.4.1.11, PMID 19093893.

Clements IP, Kim YT, English AW, Lu X, Chung A, Bellamkonda RV. Thin film enhanced nerve guidance channels for peripheral nerve repair. Biomaterials. 2009;30(23-24):3834-46. doi: 10.1016/j.biomaterials.2009.04.022, PMID 19446873.

Kim YT, Haftel VK, Kumar S, Bellamkonda RV. The role of aligned polymer fiber based constructs in the bridging of long peripheral nerve gaps. Biomaterials. 2008;29(21):3117-27. doi: 10.1016/j.biomaterials.2008.03.042, PMID 18448163.

Lietz M, Dreesmann L, Hoss M, Oberhoffner S, Schlosshauer B. Neuro tissue engineering of glial nerve guides and the impact of different cell types. Biomaterials. 2006;27(8):1425-36. doi: 10.1016/j.biomaterials.2005.08.007, PMID 16169587.

Xu J, Jiao Y, Shao X, Zhou C. Controlled dual release of hydrophobic and hydrophilic drugs from electrospun poly(l-lactic acid) fiber mats loaded with chitosan microspheres. Materials Letters. 2011;65(17-18):2800-3. doi: 10.1016/j.matlet.2011.06.018.

Song B, Wu C, Jiang Chang. Controllable delivery hydrophilic hydrophobic drugs electrospun poly (lactic‐co‐glycolic acid)/mesoporous silica nanoparticles composite mats. J Biomed Mater Res B Appl Biomater. 2012 Nov;100(8):2178-86. doi: 10.1002/jbm.b.32785.

Martin CR. Membrane based synthesis of nanomaterials. Chem Mater. 1996;8(8):1739-46. doi: 10.1021/cm960166s.

Ma PX, R Zhang. Synthetic nano‐scale fibrous extracellular matrix. J Biomed Mater Res. 1999;46(1):60-72. doi: 10.1002/(sici)1097-4636(199907)46:1<60::aid-jbm7>3.0.co;2-h.

Hartgerink JD, Beniash E, Stupp SI. Self assembly and mineralization of peptide amphiphile nanofibers. Science. 2001;294(5547):1684-8. doi: 10.1126/science.1063187, PMID 11721046.

Hassan MA, Yeom BY, Wilkie A, Pourdeyhimi B, Khan SA. Fabrication of nanofiber meltblown membranes and their filtration properties. Journal of Membrane Science. 2013 Jan 15;427:336-44. doi: 10.1016/j.memsci.2012.09.050.

Heunis TD, Dicks LM. Nanofibers offer alternative ways to the treatment of skin infections. J Biomed Biotechnol. 2010;2010:510682. doi: 10.1155/2010/510682, PMID 20798871.

Rozek Z. Potential applications of nanofiber textile covered by carbon coatings. Journal of Achievements of Materials and Manufacturing Engineering. 2008;27(1):35-8.

KO J, Bhullar SK, Mohtaram NK, Willerth SM, Jun MB. Using mathematical modeling to control topographical properties of poly (ε-caprolactone) melt electrospun scaffolds. J Micromech Microeng. 2014;24(6):65009. doi: 10.1088/0960-1317/24/6/065009.

Tutak W, Sarkar S, Lin Gibson S, Farooque TM, Jyotsnendu G, Wang D. The support of bone marrow stromal cell differentiation by airbrushed nanofiber scaffolds. Biomaterials. 2013;34(10):2389-98. doi: 10.1016/j.biomaterials.2012.12.020, PMID 23312903.

Nematpour N, Farhadian N, Ebrahimi KS, Arkan E, Seyedi F, Khaledian S. Sustained release nanofibrous composite patch for transdermal antibiotic delivery. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2020 Feb 5;586:124267. doi: 10.1016/j.colsurfa.2019.124267.

Gupta KC, Haider A, Choi YR, Kang IK. Nanofibrous scaffolds in biomedical applications. Biomater Res. 2014;18(1):5. doi: 10.1186/2055-7124-18-5, PMID 26331056.

Kataria K, Gupta A, Rath G, Mathur RB, Dhakate SR. In vivo wound healing performance of drug loaded electrospun composite nanofibers transdermal patch. Int J Pharm. 2014;469(1):102-10. doi: 10.1016/j.ijpharm.2014.04.047, PMID 24751731.

Schulte Werning LV, Murugaiah A, Singh B, Johannessen M, Engstad RE, Skalko Basnet N. Multifunctional nanofibrous dressing with antimicrobial and anti-inflammatory properties prepared by needle-free electrospinning. Pharmaceutics. 2021;13(9):1527. doi: 10.3390/pharmaceutics13091527, PMID 34575602.

Ajalloueian F, Asgari S, Guerra PR, Chamorro CI, Ilchenco O, Piqueras S. Amoxicillin loaded multilayer pullulan based nanofibers maintain long term antibacterial properties with tunable release profile for topical skin delivery applications. Int J Biol Macromol. 2022 Aug 31;215:413-23. doi: 10.1016/j.ijbiomac.2022.06.054, PMID 35700845.

Abdoli M, Sadrjavadi K, Arkan E, Zangeneh MM, Moradi S, Zangeneh A. Polyvinyl alcohol/Gum tragacanth/graphene oxide composite nanofiber for antibiotic delivery. Journal of Drug Delivery Science and Technology. 2020 Dec;60:102044. doi: 10.1016/j.jddst.2020.102044.

Soleiman Dehkordi E, Reisi Vanani V, Hosseini S, Lorigooini Z, Zvareh VA, Farzan M. Multilayer PVA/gelatin nanofibrous scaffolds incorporated with tanacetum polycephalum essential oil and amoxicillin for skin tissue engineering application. Int J Biol Macromol. 2024;262(1):129931. doi: 10.1016/j.ijbiomac.2024.129931, PMID 38331079.

Azimi B, Ricci C, Macchi T, Gunday C, Munafo S, Maleki H. A straightforward method to produce multi-nanodrug delivery systems for transdermal/tympanic patches using electrospinning and electrospray. Polymers. 2023;15(17):3494. doi: 10.3390/polym15173494, PMID 37688120.

Patil PB, Datir SK, Saudagar RB. A review on topical gels as drug delivery system. J Drug Delivery Ther. 2019;9(3-s):989-94. doi: 10.22270/jddt.v9i3-s.2930.

Fung L, Banker G, Chodes C. Modern pharmaceutics. New York: Marcel Dekker; 1990.

Ansel HC, Popovich NG, Allen LV. Pharmaceutical dosage forms and drug delivery systems. Lippincott Williams & Wilkins; 1995.

Kaur LP. Topical gels: a review. World Journal of Pharmacy and Pharmaceutical Research. 2010;3(1):17-24.

Pena LJ. Intoduction to dosage forms and formulations. Sci Gel Dosage Forms Theor Formulation Process. 1990;42:381-8.

Osborne DW, Amann AH. Topical drug delivery formulations. Informa Health Care; 1989.

Jaglal Y. Formulation of pH-responsive lipid polymer hybrid nanoparticles for co-delivery and enhanced antibacterial activity of 18β-glycyrrhetinic acid and vancomycin against MRSA; 2020.

Otto W, Drahoslav LJ. Hydrophilic gels in biologic use. Nature 1960;185:117-8. doi: 10.1038/185117a0.

Tsuruta T. Biomedical applications of polymeric materials. CRC press; 1993.

Peppas NA. Hydrogels in pharmaceutical formulations. European Journal of Pharmaceutics and Biopharmaceutics. 2000;50(1):27-46. doi: 10.1016/S0939-6411(00)00090-4.

Bhattarai N, J Gunn, M Zhang. Chitosan based hydrogels control localized drug deliv. Advanced Drug Delivery Reviews. 2010;62(1):83-99. doi: 10.1016/j.addr.2009.07.019.

Hoffman AS. Hydrogels for biomedical applications. Advanced Drug Delivery Reviews. 2012 Dec;64:18-23. doi: 10.1016/j.addr.2012.09.010.

Gao Y, Hao Y, Zhang W, Wei Y, Shu Y, Wang J. Microwave triggered ionic liquid based hydrogel dressing with excellent hyperthermia and transdermal drug delivery performance. Chemical Engineering Journal. 2022 Feb 1;429:131590. doi: 10.1016/j.cej.2021.131590.

Bayramoglu G, Arıca MY. A novel pH sensitive porous membrane carrier for various biomedical applications based on pHEMA/chitosan: preparation and its drug release characteristics. In: Macromolecular symposia. Wiley Online Library; 2003.

Thakkar V, Korat V, Baldaniya L, Gohel M, Gandhi T, Patel N. Development and characterization of novel hydrogel containing antimicrobial drug for treatment of burns. Int J Pharm Investig. 2016;6(3):158-68. doi: 10.4103/2230-973X.187343, PMID 27606259.

Kwon TK, Hong SK, Kim JC. In vitro skin permeation of cubosomes containing triclosan. Journal of Industrial and Engineering Chemistry. 2012;18(1):563-7. doi: 10.1016/j.jiec.2011.11.031.

Esposito E, Eblovi N, Rasi S, Drechsler M, Di Gregorio GM, Menegatti E. Lipid based supramolecular systems for topical application: a preformulatory study. AAPS PharmSci. 2003;5(4):E30. doi: 10.1208/ps050430, PMID 15198518.

Esposito E, Cortesi R, Drechsler M, Paccamiccio L, Mariani P, Contado C. Cubosome dispersions as delivery systems for percutaneous administration of indomethacin. Pharm Res. 2005;22(12):2163-73. doi: 10.1007/s11095-005-8176-x, PMID 16267633.

Afzal S, Barkat K, Ashraf MU, Khalid I, Mehmood Y, Shah NH. Formulation and characterization of polymeric cross-linked hydrogel patches for topical delivery of antibiotic for healing wound infections. Polymers. 2023;15(7):1652. doi: 10.3390/polym15071652, PMID 37050266.

Andrianopoulou A, Sokolowski K, Wenzler E, Bulman ZP, Gemeinhart RA. Assessment of antibiotic release and antibacterial efficacy from pendant glutathione hydrogels using ex vivo porcine skin. J Control Release. 2024;365:936-49. doi: 10.1016/j.jconrel.2023.12.008, PMID 38070603.

Yeh YW, Huang CC, Kuo WS, Liao TL, Tsai TL, Wu PC. Multifunctional hydrogel dressing that carries three antibiotics simultaneously and enables real time ultrasound bacterial colony detection. ACS Omega. 2023;8(11):10278-87. doi: 10.1021/acsomega.2c07806, PMID 36969425.

Jarman E, Burgess J, Sharma A, Hayashigatani K, Singh A, Fox P. Human derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms. PLOS One. 2024;19(5):e0303039. doi: 10.1371/journal.pone.0303039, PMID 38701045.

Welton TJ. Room temperature ionic liquids solvents for synthesis and catalysis. Chem Rev. 1999;99(8):2071-84. doi: 10.1021/cr980032t, PMID 11849019.

Sheldon RJ. Catalytic reactions in ionic liquids. Chem Commun (Camb). 2001;(23):2399-407. doi: 10.1039/b107270f, PMID 12239988.

Endres F. Air and water stable ionic liquids in physical chemistry. Physical Chemistry Chemical Physics. 2006;8(18):2101-16. doi: 10.1039/b600519p.

Freemantle M. An introduction to ionic liquids. Royal Society of Chemistry; 2010. p. 1-25.

Zakrewsky M, Lovejoy KS, Kern TL, Miller TE, Le V, Nagy A. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proc Natl Acad Sci U S A. 2014;111(37):13313-8. doi: 10.1073/pnas.1403995111, PMID 25157174.

Sheth NS, RB Mistry. Formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol. Journal of Applied Pharmaceutical Science. 2011;1(3):96-101.

Salamanca CH, Barrera Ocampo A, Lasso JC, Camacho N, Yarce CJ. Franz diffusion cell approach for pre-formulation characterisation of ketoprofen semi-solid dosage forms. Pharmaceutics. 2018;10(3):148. doi: 10.3390/pharmaceutics10030148, PMID 30189634.

Lee JD, Kim JY, Jang HJ, Lee BM, Kim KB. Percutaneous permeability of 1-phenoxy-2-propanol a preservative in cosmetics. Regul Toxicol Pharmacol. 2019 Apr;103:56-62. doi: 10.1016/j.yrtph.2019.01.002, PMID 30611821.

Rajitha P, Shammika P, Aiswarya S, Gopikrishnan A, Jayakumar R, Sabitha M. Chaulmoogra oil based methotrexate loaded topical nanoemulsion for the treatment of psoriasis. Journal of Drug Delivery Science and Technology. 2019 Feb;49:463-76. doi: 10.1016/j.jddst.2018.12.020.

Escobar Chavez JJ, Merino Sanjuan V, Lopez Cervantes M, Urban Morlan Z, Pinon Segundo E, Quintanar Guerrero D. The tape stripping technique as a method for drug quantification in skin. J Pharm Pharm Sci. 2008;11(1):104-30. doi: 10.18433/j3201z, PMID 18445368.

Russell, LM, RH Guy. Novel imaging method quantify stratum corneum dermatopharmacokinetic s studies: proof of concept with acyclovir formulations. Pharm Res. 2012;29(12):3362-72. doi: 10.1007/s11095-012-0831-4.

Gu Y, Yang M, Tang X, Wang T, Yang D, Zhai G. Lipid nanoparticles loading triptolide for transdermal delivery: mechanisms of penetration enhancement and transport properties. J Nanobiotechnology. 2018;16(1):68. doi: 10.1186/s12951-018-0389-3, PMID 30217198.

Ahn J, Kim KH, Choe K, Lim JH, Lee SK, Kim YS. Quantitative two-photon microscopy imaging analysis of human skin to evaluate enhanced transdermal delivery by hybrid type multi-lamellar nanostructure. Biomed Opt Express. 2018;9(8):3974-82. doi: 10.1364/BOE.9.003974, PMID 30338168.

Berekmeri A, Tiganescu A, Alase AA, Vital E, Stacey M, Wittmann M. Non-invasive approaches for the diagnosis of autoimmune/autoinflammatory skin diseases a focus on psoriasis and lupus erythematosus. Front Immunol. 2019 Aug 21;10:1931. doi: 10.3389/fimmu.2019.01931, PMID 31497014.

Ashtikar M, Matthaus C, Schmitt M, Krafft C, Fahr A, Popp J. Non-invasive depth profile imaging of the stratum corneum using confocal raman microscopy: first insights into the method. Eur J Pharm Sci. 2013;50(5):601-8. doi: 10.1016/j.ejps.2013.05.030, PMID 23764946.

Zhang LW, NA Monteiro Riviere. Use confocal microsc nanopart drug deliv skin. J Biomed Opt. 2012 Jun;18(6):61214. doi 10.1117/1.JBO.18.6.061214.