title: Skin transport of PEGylated poly(ε-caprolactone) nanoparticles assisted by (2-hydroxypropyl)-β-cyclodextrin.
abstract: The aim of this work was to investigate the potential of small nanoparticles (NPs) made of a poly(ethylene glycol)-poly(ε-caprolactone)-amphiphilic diblock copolymer (PEG-b-PCL, PEG=2kDa and PCL=4.2kDa) as drug carrier system through the skin. Zinc(II) phthalocyanine (ZnPc), selected as lipophilic and fluorescent model molecule, was loaded inside NPs by a melting/sonication procedure. Loaded NPs with a hydrodynamic diameter around 60nm, a slightly negative zeta potential and a ZnPc entrapment dependent on polymer/ZnPc ratio were obtained. Spectroscopic investigations evidenced that ZnPc was entrapped in monomeric form maintaining its emission properties. The transport of ZnPc through porcine ear skin was evaluated on Franz-type diffusion cells after treatment with different vehicles (water or PEG 0.4kDa) containing free ZnPc or ZnPc-loaded NPs without and with (2-hydroxypropyl)-β-cyclodextrin (HPβCD) as permeation enhancer. Independently of the sample tested, ZnPc was transported in the skin without reaching receptor compartment. On the other hand, ZnPc was found in the skin in large amount and also in the viable epidermis when delivered through NPs associated with HPβCD, especially in conditions limiting water evaporation. Fluorescence images of skin samples after 24h of permeation were in line with ZnPc dosage in the skin and demonstrated the ability of NPs covalently tagged with rhodamine to penetrate the skin and to locate in the intercellular spaces. Insight into skin chemical properties upon application of NPs by confocal Raman spectroscopy demonstrated that HPβCD caused an alteration of water profile in the skin, highly reducing the degree of hydration at stratum corneum/viable epidermis interface which can promote NP transport. Taken together, these results highlight PEG-b-PCL NPs coupled with HPβCD as a novel vehicle for the skin delivery of highly lipophilic compounds paving the way to several applications.
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Conte
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Costabile
authors.affiliation: Second University of Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: d'Angelo
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, via Campi Flegrei, 34, 80078 Pozzuoli, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Pannico
authors.affiliation: Institute for Polymers, Composites and Biomaterials, National Research Council of Italy, via Campi Flegrei, 34, 80078 Pozzuoli, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Grassia
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Armando
authors.initials: A
authors.lastname: Ialenti
authors.affiliation: Department of Chemistry Paolo Corradini, University of Napoli Federico II, Via Cintia, 80126 Napoli, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Tirino
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Miro
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ungaro
authors.affiliation: Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesano 49, 80131 Napoli, Italy.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quaglia
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D001692:Biological Transport; D004337:Drug Carriers; D004339:Drug Compounding; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D054833:Isoindoles; D007783:Lactones / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000494:pharmacology; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013010:Sonication; D055672:Static Electricity; D013552:Swine; D046509:Tissue Culture Techniques; D014867:Water / Q000737:chemistry / Q000378:metabolism; D017967:Zinc Compounds; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004337:Drug Carriers; D005456:Fluorescent Dyes; D007211:Indoles; D054833:Isoindoles; D007783:Lactones; D009942:Organometallic Compounds; D017967:Zinc Compounds; D047392:beta-Cyclodextrins; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D014867:Water; C052159:Zn(II)-phthalocyanine; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D011092:Polyethylene Glycols
keywords: Cyclodextrin; Fluorescence; PEGylated nanoparticles; Raman; Skin