title: Protein transduction domain-containing microemulsions as cutaneous delivery systems for an anticancer agent.
abstract: In this study, we developed cationic microemulsions containing a protein transduction domain (penetratin) for optimizing paclitaxel localization within the skin. Microemulsions were prepared by mixing a surfactant blend (BRIJ:ethanol:propylene glycol 2:1:1, w/w/w) with monocaprylin (oil phase) at 1.3:1 ratio, and adding water at 30% (ME-30), 43% (ME-43), and 50% (ME-50). Electrical conductivity and viscosity measurements indicated that ME-30 is most likely a bicontinuous system, whereas ME-43 and ME-50 are water continuous. Their irritation potential, studied in bioengineered skin equivalents, decreased as aqueous content increased. Because ME-50 was not stable in the presence of paclitaxel (0.5%), ME-43 was selected for penetratin incorporation (0.4%). The microemulsion containing penetratin (ME-P) displayed zeta potential of +5.2 mV, and promoted a 1.8-fold increase in paclitaxel cutaneous (but not transdermal) delivery compared with the plain ME-43, whereas the enhancement promoted by another cationic microemulsion containing phytosphingosine was 1.3-fold. Compared with myvacet oil, ME-P promoted a larger increase on transepidermal water loss (twofold) than the plain or the phytosphingosine-containing microemulsions (1.5-fold), suggesting that penetratin addition increases the barrier-disrupting and penetration-enhancing effects of microemulsions. The ratio Δcutaneous/Δtransdermal delivery promoted by ME-P was the highest among the formulations, suggesting its potential for drug localization within cutaneous tumor lesions.
authors: Albany College of Pharmacy and Health Sciences, Albany, New York 12208, USA.
authors: Dominique
authors: D
authors: Pepe
authors: Melissa
authors: M
authors: McCall
authors: Haian
authors: H
authors: Zheng
authors: Luciana B
authors: LB
authors: Lopes
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000279:Administration, Cutaneous; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002210:Caprylates / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D057846:Cell-Penetrating Peptides; D004655:Emulsions / Q000737:chemistry* / Q000378:metabolism; D005989:Glycerides / Q000737:chemistry / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014677:Pharmaceutical Vehicles / Q000737:chemistry* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D023422:Skin Irritancy Tests; D013110:Sphingosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism; D013552:Swine; D014867:Water / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D002210:Caprylates; D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D004655:Emulsions; D005989:Glycerides; D014677:Pharmaceutical Vehicles; D013501:Surface-Active Agents; D014867:Water; D000255:Adenosine Triphosphate; C414409:penetratin; C012491:phytosphingosine; D013110:Sphingosine; D017239:Paclitaxel; C025343:monooctanoin