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Dermal and transdermal delivery of pharmaceutically relevant macromolecules. <i>Eur. J. Pharm. Biopharm.<\/i>, <b>119<\/b>, 235\u2013242 (2017).","DOI":"10.1016\/j.ejpb.2017.06.019"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Amano N, Takaki Y, Takei H, Matsuo M, Hara M, Tashiro Y, Oniki T, Ito T, Hikima T. Fabrication and mechanical\/biological evaluations of dissolving bird-bill microneedle arrays. <i>Drug Deliv. Transl. Res.<\/i>, <b>15<\/b>, 2581\u20132588 (2025).","DOI":"10.1007\/s13346-024-01757-w"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Wang Y, Zeng L, Song W, Liu J. Influencing factors and drug application of iontophoresis in transdermal drug delivery: an overview of recent progress. <i>Drug Deliv. Transl. Res.<\/i>, <b>12<\/b>, 15\u201326 (2022).","DOI":"10.1007\/s13346-021-00898-6"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Sinico C, Manconi M, Peppi M, Lai F, Valenti D, Fadda AM. Liposomes as carriers for dermal delivery of tretinoin: in vitro evaluation of drug permeation and vesicle-skin interaction. <i>J. Control. Release<\/i>, <b>103<\/b>, 123\u2013136 (2005).","DOI":"10.1016\/j.jconrel.2004.11.020"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Desai P, Patlolla RR, Singh M. Interaction of nanoparticles and cell-penetrating peptides with skin for transdermal drug delivery. <i>Mol. Membr. Biol.<\/i>, <b>27<\/b>, 247\u2013259 (2010).","DOI":"10.3109\/09687688.2010.522203"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Morrow DIJ, McCarron PA, Woolfson AD, Donnelly RF. Innovative strategies for enhancing topical and transdermal drug delivery. <i>Open Drug Deliv. J.<\/i>, <b>1<\/b>, 36\u201359 (2007).","DOI":"10.2174\/1874126600701010036"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Salau O, Bagde A, Kalvala A, Singh M. Enhancement of transdermal permeation of cannabinoids and their pharmacodynamic evaluation in rats. <i>Int. J. Pharm.<\/i>, <b>624<\/b>, 122016 (2022).","DOI":"10.1016\/j.ijpharm.2022.122016"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Virani A, Puri V, Mohd H, Michniak-Kohn B. Effect of penetration enhancers on transdermal delivery of oxcarbazepine, an antiepileptic drug using microemulsions. <i>Pharmaceutics<\/i>, <b>15<\/b>, 183 (2023).","DOI":"10.3390\/pharmaceutics15010183"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Monti D, Egiziano E, Burgalassi S, Chetoni P, Chiappe C, Sanzone A, Tampucci S. Ionic liquids as potential enhancers for transdermal drug delivery. <i>Int. J. Pharm.<\/i>, <b>516<\/b>, 45\u201351 (2017).","DOI":"10.1016\/j.ijpharm.2016.11.020"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Gao W, Xing W, Tang Z, Wang Q, Yu W, Zhang Q. Ionic liquid-iontophoresis mediates transdermal delivery of sparingly soluble drugs. <i>Drug Deliv.<\/i>, <b>32<\/b>, 2489730 (2025).","DOI":"10.1080\/10717544.2025.2489730"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Szuma\u0142a P, Jungnickel C, Koz\u0142owska-Tylingo K, Jacyna B, Cal K. Transdermal transport of collagen and hyaluronic acid using water in oil microemulsion. <i>Int. J. Pharm.<\/i>, <b>572<\/b>, 118738 (2019).","DOI":"10.1016\/j.ijpharm.2019.118738"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Xing H, Pan X, Hu Y, Yang Y, Zhao Z, Peng H, Wang J, Li S, Hu Y, Li G, Ma D. High molecular weight hyaluronic acid-liposome delivery system for efficient transdermal treatment of acute and chronic skin photodamage. <i>Acta Biomater.<\/i>, <b>182<\/b>, 171\u2013187 (2024).","DOI":"10.1016\/j.actbio.2024.05.026"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Elizarova IS, Luckham RF. Layer-by-layer adsorption: factors affecting the choice of substrates and polymers. <i>Adv. Colloid Interface Sci.<\/i>, <b>262<\/b>, 1\u201320 (2018).","DOI":"10.1016\/j.cis.2018.11.003"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Mirchandani Y, Patravale VB, Brijesh S. Solid lipid nanoparticles for hydrophilic drugs. <i>J. Control. Release<\/i>, <b>335<\/b>, 457\u2013464 (2021).","DOI":"10.1016\/j.jconrel.2021.05.032"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Mehnert W, Mader K. Solid lipid nanoparticles: production, characterization and applications. <i>Adv. Drug Deliv. Rev.<\/i>, <b>47<\/b>, 165\u2013196 (2001).","DOI":"10.1016\/S0169-409X(01)00105-3"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) M\u00fcller RH, Radtke M, Wissing SA. Nanostructured lipid matrices for improved microencapsulation of drugs. <i>Int. J. Pharm.<\/i>, <b>242<\/b>, 121\u2013128 (2002).","DOI":"10.1016\/S0378-5173(02)00180-1"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Essaghraoui A, Belfkira A, Hamdaoui B, Nunes C, Lima SAC, Reis S. Improved dermal delivery of cyclosporine A loaded in solid lipid nanoparticles. <i>Nanomaterials<\/i>, <b>9<\/b>, 1204 (2019).","DOI":"10.3390\/nano9091204"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Sakai T, Sodemoto N, Inoue A, Taniguchi S, Maeda I, Hikima T. Suitability of high-molecular-weight tissue-derived elastin polypeptides and their particles as cosmetic biomaterials. <i>J. Pept. Sci.<\/i>, <b>29<\/b>, e3472 (2023).","DOI":"10.1002\/psc.3472"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Hikima T, Tamura Y, Yamawaki Y, Yamamoto M, Tojo K. Skin accumulation and penetration of a hydrophilic compound by a novel gemini surfactant, sodium dilauramidoglutamide lysine. <i>Int. J. Pharm.<\/i>, <b>443<\/b>, 288\u2013292 (2013).","DOI":"10.1016\/j.ijpharm.2012.12.034"},{"key":"20","unstructured":"20) Shimizu M, Yamamoto K, Hamayama S, U.S. Patent US10,441,935 B2 (2019) \u2039https:\/\/www.j-platpat.inpit.go.jp\/c1801\/PU\/US-B-010441935\/50\/ja\u203a, accessed 18 July, 2025."},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: a key molecule in skin aging. <i>Dermatoendocrinol.<\/i>, <b>4<\/b>, 253\u2013258 (2012).","DOI":"10.4161\/derm.21923"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Tojo K, Yamada K, Hikima T. Diffusion and metabolism of prednisolone farnesylate in viable skin of the hairless mouse. <i>Pharm. Res.<\/i>, <b>11<\/b>, 393\u2013397 (1994).","DOI":"10.1023\/A:1018960920313"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Hikima T, Tojo K. Binding of prednisolone and its ester prodrugs in the skin. <i>Pharm. 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Release<\/i>, <b>62<\/b>, 201\u2013208 (1999).","DOI":"10.1016\/S0168-3659(99)00039-5"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Chen W, Palazzo A, Hennink WE, Kok RJ. Effect of particle size on drug loading and release kinetics of Gefitinib-loaded PLGA microspheres. <i>Mol. Pharm.<\/i>, <b>14<\/b>, 459\u2013467 (2017).","DOI":"10.1021\/acs.molpharmaceut.6b00896"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Tokudome Y, Komi T, Omata A, Sekita M. A new strategy for the passive skin delivery of nanoparticulate, high molecular weight hyaluronic acid prepared by a polyion complex method. <i>Sci. Rep.<\/i>, <b>8<\/b>, 2336 (2018).","DOI":"10.1038\/s41598-018-20805-3"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Mishra H, Mishra PK, Iqbal Z, Jaggi M, Madaan A, Bhuyan K, Gupta N, Gupta N, Vats K, Verma R, Talegaonkar S. Co-delivery of eugenol and dacarbazine by hyaluronic acid-coated liposomes for targeted inhibition of survivin in treatment of resistant metastatic melanoma. <i>Pharmaceutics<\/i>, <b>11<\/b>, 163 (2019).","DOI":"10.3390\/pharmaceutics11040163"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Verma DD, Verma S, Blume G, Fahr A. Particle size of liposomes influences dermal delivery of substances into skin. <i>Int. J. Pharm.<\/i>, <b>258<\/b>, 141\u2013151 (2003).","DOI":"10.1016\/S0378-5173(03)00183-2"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Sato T, Takeuchi H, Sakurai T, Tanaka K, Matsuki K, Higashi K, Moribe K, Yamamoto K. Characterization of a riboflavin non-aqueous nanosuspension prepared by bead milling for cutaneous application. <i>Chem. Pharm. Bull.<\/i>, <b>63<\/b>, 88\u201394 (2015).","DOI":"10.1248\/cpb.c14-00641"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Witting M, Boreham A, Brodwolf R, V\u00e1vrov\u00e1 K, Alexiev U, Friess W, Hedtrich S. Interactions of hyaluronic acid with the skin and implications for the dermal delivery of biomacromolecules. <i>Mol. Pharm.<\/i>, <b>12<\/b>, 1391\u20131401 (2015).","DOI":"10.1021\/mp500676e"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) D\u00edaz-Valenzuela A, Garc\u00eda-Fern\u00e1ndez FP, Carmona Fern\u00e1ndez PJ, Valle Ca\u00f1ete MJ, Pancorbo-Hidalgo PL. Effectiveness and safety of olive oil preparation for topical use in pressure ulcer prevention: Multicentre, controlled, randomised, and double-blinded clinical trial. <i>Int. Wound J.<\/i>, <b>16<\/b>, 1314\u20131322 (2019).","DOI":"10.1111\/iwj.13191"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Kozaka S, Kashima A, Wakabayashi R, Nakata T, Ueda T, Goto M. 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