title: Translocation of cell penetrating peptide engrafted nanoparticles across skin layers.
abstract: The objective of the current study was to evaluate the ability of cell penetrating peptides (CPP) to translocate the lipid payload into the skin layers. Fluorescent dye (DID-oil) encapsulated nano lipid crystal nanoparticles (FNLCN) were prepared using Compritol, Miglyol and DOGS-NTA-Ni lipids by hot melt homogenization technique. The FNLCN surface was coated with TAT peptide (FNLCNT) or control YKA peptide (FNLCNY) and in vitro rat skin permeation studies were performed using Franz diffusion cells. Observation of lateral skin sections obtained using cryotome with a confocal microscope demonstrated that skin permeation of FNLCNT was time dependent and after 24h, fluorescence was observed upto a depth of 120 microm which was localized in the hair follicles and epidermis. In case of FNLCN and FNLCNY formulations fluorescence was mainly observed in the hair follicles. This observation was further supported by confocal Raman spectroscopy where higher fluorescence signal intensity was observed at 80 and 120 microm depth with FNLCNT treated skin and intensity of fluorescence peaks was in the ratio of 2:1:1 and 5:3:1 for FNLCNT, FNLCN, and FNLCNY treated skin sections, respectively. Furthermore, replacement of DID-oil with celecoxib (Cxb), a model lipophilic drug showed similar results and after 24h, the CXBNT formulation increased the Cxb concentration in SC by 3 and 6 fold and in epidermis by 2 and 3 fold as compared to CXBN and CXBNY formulations respectively. Our results strongly suggest that CPP can translocate nanoparticles with their payloads into deeper skin layers.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Ram R
authors.initials: RR
authors.lastname: Patlolla
authors.forename: Pinaki R
authors.initials: PR
authors.lastname: Desai
authors.forename: Kalayu
authors.initials: K
authors.lastname: Belay
authors.forename: Mandip S
authors.initials: MS
authors.lastname: Singh
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D015696:Gene Products, tat / Q000737:chemistry; D006801:Humans; D008239:Lysine / Q000031:analogs & derivatives / Q000737:chemistry; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D009829:Oleic Acids / Q000737:chemistry; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D013386:Succinates / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D004337:Drug Carriers; D005456:Fluorescent Dyes; D015696:Gene Products, tat; C476561:N(alpha),N(alpha)-bis(carboxymethyl)-N(epsilon)-(1,2-dioleyl-sn-glycero-3-succinyl)-L-lysine; D009829:Oleic Acids; D010455:Peptides; D013386:Succinates; D008239:Lysine