{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:44:51Z","timestamp":1791654291626,"version":"4.3.4"},"reference-count":140,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Northern Border University","award":["NBU-FFR-2026-3122-01"],"award-info":[{"award-number":["NBU-FFR-2026-3122-01"]}]},{"award":["NBU-FFR-2026-3122-01"],"award-info":[{"award-number":["NBU-FFR-2026-3122-01"]}],"id":[{"id":"https:\/\/ror.org\/03j9tzj20","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid\u2013polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments.<\/jats:p>","DOI":"10.3390\/ph19071057","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T14:27:23Z","timestamp":1783520843000},"page":"1057","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nanotechnologies for Skin Drug Delivery: Polymeric, Bio-Based, and Hybrid Nanocarriers with Clinical and Translational Perspectives"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8885-7903","authenticated-orcid":false,"given":"Lina","family":"Eltaib","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 73213, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0125-7073","authenticated-orcid":false,"given":"Hamoud","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 73213, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona Al","family":"Hamod","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Northern Border University, Rafha 73213, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Alfuraih","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Northern Border University, Rafha 76313, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0346-5754","authenticated-orcid":false,"given":"Noura Al","family":"Hamood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0640-4228","authenticated-orcid":false,"given":"Ahmad Mohammad","family":"Balkhair","sequence":"additional","affiliation":[{"name":"Department of Nano-Medicine Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7391-3228","authenticated-orcid":false,"given":"Abdullah Abdulrahman","family":"Aljasser","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e202107960","DOI":"10.1002\/anie.202107960","article-title":"Nanocarriers for skin applications: Where do we stand?","volume":"61","author":"Tiwari","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Brito, S., Baek, M., and Bin, B.H. (2024). Skin structure, physiology, and pathology in topical and transdermal drug delivery. 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