title: Doxorubicin liposomes as an investigative model to study the skin permeation of nanocarriers.
abstract: The objectives of this study were to develop an innovative investigative model using doxorubicin as a fluorophore to evaluate the skin permeation of nanocarriers and the impact of size and surface characteristics on their permeability. Different doxorubicin-loaded liposomes with mean particle size <130 nm and different surface chemistry were prepared by ammonium acetate gradient method using DPPC, DOPE, Cholesterol, DSPE-PEG 2000 and 1,1-Di-((Z)-octadec-9-en-1-yl) pyrrolidin-1-ium chloride (CY5)/DOTAP/1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) as the charge modifier. There was minimal release of doxorubicin from the liposomes up to 8h; indicating that fluorescence observed within the skin layers was due to the intact liposomes. Liposomes with particle sizes >600 nm were restricted within the stratum corneum. DOTAP (p<0.01) and CY5 (p<0.05) liposomes demonstrated significant permeation into the skin than DOPA and PEG liposomes. Tape stripping significantly (p<0.01) enhanced the skin permeation of doxorubicin liposomes but TAT-decorated doxorubicin liposomes permeated better (p<0.005). Blockage of the hair follicles resulted in significant reduction in the extent and intensity of fluorescence observed within the skin layers. Overall, doxorubicin liposomes proved to be an ideal fluorophore-based model. The hair follicles were the major route utilized by the liposomes to permeate skin. Surface charge and particle size played vital roles in the extent of permeation.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Cedar H A
authors.initials: CH
authors.lastname: Boakye
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
authors.forename: Ketan
authors.initials: K
authors.lastname: Patel
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. Electronic address: mandip.sachdeva@gmail.com.
authors.forename: Mandip
authors.initials: M
authors.lastname: Singh
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage / Q000737:chemistry; D003374:Coumarins / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D015696:Gene Products, tat / Q000008:administration & dosage / Q000737:chemistry; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D008297:Male; D010539:Permeability; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000903:Antibiotics, Antineoplastic; D057846:Cell-Penetrating Peptides; D003374:Coumarins; D004337:Drug Carriers; D005456:Fluorescent Dyes; D015696:Gene Products, tat; D008055:Lipids; D034741:RNA, Small Interfering; D013844:Thiazoles; C517282:coumarin 6; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D016650:Fluorescein-5-isothiocyanate
keywords: 1,2-Dioleoyl-3-trimethylammonium-propane (chloride salt); 1,2-Dioleoyl-sn-glycero-3-[(N-(5-amino-1-carboxypentyl) imidodiacetic acid) succinyl nickel salt]; 1,2-Dioleoyl-sn-glycero-3-phosphate; 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine; 1,2-Dipalmitoyl-sn-glycero-3-Phosphocholine; 1,2-Distearoyl-sn-glycero-3-Phosphoethanolamine-N-[amino(polyethyleneglycol)-2000] (ammonium salt); Cell penetrating peptides; Coumarin 6; Doxorubicin HCL; Doxorubicin liposomes; Hair follicle blocking; Polyethylene glycol; Skin permeation; Tape stripping; Topical drug delivery