title: Sustained epidermal powder drug delivery via skin microchannels.
abstract: Transdermal delivery of hydrophilic drugs is challenging. This study presents a novel sustained epidermal powder delivery technology (sEPD) for safe, efficient, and sustained delivery of hydrophilic drugs across the skin. sEPD is based on coating powder drugs into high-aspect-ratio, micro-coating channels (MCCs) followed by topical application of powder drug-coated array patches onto ablative fractional laser-generated skin MCs to deliver drugs into the skin. We found sEPD could efficiently deliver chemical drugs without excipients and biologics drugs in the presence of sugar excipients into the skin with a duration of ~12h. Interestingly the sEPD significantly improved zidovudine bioavailability by ~100% as compared to oral gavage delivery. sEPD of insulin was found to maintain blood glucose levels in normal range for at least 6h in chemical-induced diabetes mice, while subcutaneous injection failed to maintain blood glucose levels in normal range. sEPD of anti-programmed death-1 antibody showed more potent anti-tumor efficacy than intraperitoneal injection in B16F10 melanoma models. Tiny skin MCs and 'bulk' drug powder inside relatively deep MCCs are crucial to induce the sustained drug release. The improved bioavailability and functionality warrants further development of the novel sEPD for clinical use.
authors.affiliation: Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Pharmacy Building, Room 480, Kingston, RI 02881, United States.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Pharmacy Building, Room 480, Kingston, RI 02881, United States.
authors.forename: Prateek
authors.initials: P
authors.lastname: Kakar
authors.affiliation: Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Pharmacy Building, Room 480, Kingston, RI 02881, United States.
authors.forename: Md Nazir
authors.initials: MN
authors.lastname: Hossen
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, 50 Blossom Street, Boston, MA 02114, United States.
authors.forename: Mei X
authors.initials: MX
authors.lastname: Wu
authors.affiliation: Biomedical & Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Pharmacy Building, Room 480, Kingston, RI 02881, United States. Electronic address: xchen14@uri.edu.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Chen
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage; D000906:Antibodies / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004817:Epidermis / Q000378:metabolism*; D004867:Equipment Design; D005456:Fluorescent Dyes / Q000008:administration & dosage; D057927:Hydrophobic and Hydrophilic Interactions; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage; D007834:Lasers; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008845:Microinjections; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D011208:Powders / Q000008:administration & dosage; D012235:Rhodamines / Q000008:administration & dosage; D012869:Skin Absorption; D015215:Zidovudine / Q000008:administration & dosage
chemical_list: D019380:Anti-HIV Agents; D000906:Antibodies; D005456:Fluorescent Dyes; D007328:Insulin; D004364:Pharmaceutical Preparations; D011208:Powders; D012235:Rhodamines; C022027:lissamine rhodamine B; D015215:Zidovudine
keywords: Laser; Microchannel; Microneedle; Microporation; Micropore; Transdermal drug delivery