title: Cutaneous penetration of soft nanoparticles via photodamaged skin: Lipid-based and polymer-based nanocarriers for drug delivery.
abstract: Photoaging is recognized as the factor damaging skin-barrier function. The aim of this study was to examine the impact of ultraviolet (UV) irradiation on the cutaneous penetration of soft nanoparticles, including nanostructured lipid carriers (NLCs) and poly(lactic-co-glycolic acid) polymer nanoparticles (PNs). In vitro cutaneous permeation of retinoic acid (RA) carried by nanoparticles was evaluated. In vivo nude mouse skin distribution of topically applied nanoparticles was observed by fluorescence and confocal microscopies. The association of nanoparticles with cultured keratinocytes was measured by flow cytometry and fluorescence microscopy. The average diameter and surface charge were 236nm and -32mV for NLCs, and 207nm and -12mV for PNs. The ultrastructural images of skin demonstrated that the application of UV produced a loss of Odland bodies and desmosomes, the organelles regulating skin-barrier function. UVA exposure increased skin deposition of RA regardless of nanoparticle formulation. UVB did not alter RA deposition from nanoparticles as compared to the non-treated group. Exposure to UVA promoted RA delivery into hair follicles from NLCs and PNs by 4.2- and 4.9-fold, respectively. The in vivo skin distribution also showed a large accumulation of Nile red-loaded nanoparticles in follicles after UVA treatment. The soft nanoparticles were observed deep in the dermis. PNs with higher lipophilicity showed a greater association with keratinocytes compared to NLCs. The cell association of PNs was increased by UVA application, whereas the association between NLCs and keratinocytes was reduced two times by UVA. It was concluded that both follicles and intercellular spaces were the main pathways for nanoparticle diffusion into photodamaged skin.
authors.affiliation: School of Medicine, Fu Jen Catholic University, Hsinchuang, New Taipei City, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Hung
authors.affiliation: Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Wei-Yu
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Health Sciences, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Hsu
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Aljuffali
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chang Gung Memorial Hospital, Kweishan, Taoyuan, Taiwan.
authors.forename: Hui-Chi
authors.initials: HC
authors.lastname: Shih
authors.affiliation: Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Kweishan, Taoyuan, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan. Electronic address: fajy@mail.cgu.edu.tw.
authors.forename: Jia-You
authors.initials: JY
authors.lastname: Fang
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D004058:Diffusion; D004337:Drug Carriers; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000648:ultrastructure; D019344:Lactic Acid / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D050997:Nanomedicine; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011859:Radiography; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D012869:Skin Absorption; D015595:Skin Aging; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D003879:Dermatologic Agents; D004337:Drug Carriers; D008055:Lipids; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D014212:Tretinoin
keywords: Cutaneous penetration; Lipid nanoparticle; Photodamage; Polymer nanoparticle; Skin