PMID- 23461860 OWN - NLM STAT- MEDLINE DCOM- 20141107 LR - 20220216 IS - 1873-3441 (Electronic) IS - 0939-6411 (Print) IS - 0939-6411 (Linking) VI - 86 IP - 2 DP - 2014 Feb TI - Microneedle/nanoencapsulation-mediated transdermal delivery: mechanistic insights. PG - 145-55 LID - S0939-6411(13)00051-9 [pii] LID - 10.1016/j.ejpb.2013.01.026 [doi] AB - A systematic study was undertaken to gain more insight into the mechanism of transdermal delivery of nanoencapsulated model dyes across microneedle (MN)-treated skin, a complex process not yet explored. Rhodamine B (Rh B) and fluorescein isothiocyanate (FITC) as model hydrophilic and hydrophobic small/medium-size molecules, respectively, were encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) and delivered through full thickness porcine skin pretreated with MN array. Permeation through MN-treated skin was affected by physicochemical characteristics of NPs and the encapsulated dyes. Dye flux was enhanced by smaller particle size, hydrophilicity, and negative zeta potential of NPs. Regarding encapsulated dyes, solubility at physiological pH and potential interaction with skin proteins proved to outweigh molecular weight as determinants of skin permeation. Data were verified using confocal laser scanning microscopy imaging. Findings coupled with the literature data are supportive of a mechanism involving influx of NPs, particularly of smaller size, deep into MN-created channels, generating depot dye-rich reservoirs. Molecular diffusion of the released dye across viable skin layers proceeds at a rate determined by its molecular characteristics. Data obtained provide mechanistic information of importance to the development of formulation strategies for more effective intradermal and transdermal MN-mediated delivery of nanoencapsulated therapeutic agents. CI - Copyright (c) 2013 Elsevier B.V. All rights reserved. FAU - Gomaa, Yasmine A AU - Gomaa YA AD - Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Scotland, UK; Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. FAU - Garland, Martin J AU - Garland MJ AD - School of Pharmacy, Queen's University of Belfast, Northern Ireland, UK. FAU - McInnes, Fiona J AU - McInnes FJ AD - Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Scotland, UK. FAU - Donnelly, Ryan F AU - Donnelly RF AD - School of Pharmacy, Queen's University of Belfast, Northern Ireland, UK. FAU - El-Khordagui, Labiba K AU - El-Khordagui LK AD - Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. Electronic address: lakhalil@alexpharmacy.edu.eg. FAU - Wilson, Clive G AU - Wilson CG AD - Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), University of Strathclyde, Scotland, UK. LA - eng GR - BB/E020534/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom GR - BBE020534/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130224 PL - Netherlands TA - Eur J Pharm Biopharm JT - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JID - 9109778 RN - 0 (Isothiocyanates) RN - 0 (Polyesters) RN - 0 (Polymers) RN - 0 (Rhodamines) RN - 3129-90-6 (isothiocyanic acid) RN - 33X04XA5AT (Lactic Acid) RN - 459TN2L5F5 (poly(lactide)) RN - K7G5SCF8IL (rhodamine B) RN - TPY09G7XIR (Fluorescein) SB - IM MH - Administration, Cutaneous MH - Animals MH - Drug Delivery Systems/methods MH - Fluorescein/administration & dosage/chemistry MH - Hydrophobic and Hydrophilic Interactions MH - Isothiocyanates/administration & dosage/chemistry MH - Lactic Acid/administration & dosage/chemistry MH - Microinjections/methods MH - Nanoparticles/*administration & dosage/*chemistry/metabolism MH - Needles MH - Particle Size MH - Permeability MH - Polyesters MH - Polymers/administration & dosage/chemistry MH - Rhodamines/administration & dosage/chemistry MH - Skin/*metabolism MH - Skin Absorption MH - Solubility MH - Swine PMC - PMC4074889 OTO - NOTNLM OT - Confocal laser scanning microscopy OT - Fluorescein isothicoyanate OT - Microneedles OT - PLGA nanoparticles OT - Rhodamine B OT - Skin permeation OT - Transdermal delivery EDAT- 2013/03/07 06:00 MHDA- 2014/11/08 06:00 PMCR- 2014/02/01 CRDT- 2013/03/07 06:00 PHST- 2012/10/28 00:00 [received] PHST- 2013/01/06 00:00 [revised] PHST- 2013/01/29 00:00 [accepted] PHST- 2013/03/07 06:00 [entrez] PHST- 2013/03/07 06:00 [pubmed] PHST- 2014/11/08 06:00 [medline] PHST- 2014/02/01 00:00 [pmc-release] AID - S0939-6411(13)00051-9 [pii] AID - 10.1016/j.ejpb.2013.01.026 [doi] PST - ppublish SO - Eur J Pharm Biopharm. 2014 Feb;86(2):145-55. doi: 10.1016/j.ejpb.2013.01.026. Epub 2013 Feb 24.