title: Investigation of the mechanism of enhanced skin penetration by ultradeformable liposomes.
abstract: This study aimed to determine the mechanism by which ultradeformable liposomes (ULs) with terpenes enhance skin penetration for transdermal drug delivery of fluorescein sodium, using transmission electron microscopy (TEM) and confocal laser scanning microscopy (CLSM). Skin treated with ULs containing d-limonene, obtained from in vitro skin penetration studies, was examined via TEM to investigate the effect of ULs on ultrastructural changes of the skin, and to evaluate the mechanism by which ULs enhance skin penetration. The receiver medium collected was analyzed by TEM and CLSM to evaluate the mechanism of the drug carrier system. Our findings revealed that ULs could enhance penetration by denaturing intracellular keratin, degrading corneodesmosomes, and disrupting the intercellular lipid arrangement in the stratum corneum. As inferred from the presence of intact vesicles in the receiver medium, ULs are also able to act as a drug carrier system. CLSM images showed that intact vesicles of ULs might penetrate the skin via a transappendageal pathway, potentially a major route of skin penetration.
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Thirapit
authors.initials: T
authors.lastname: Subongkot
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Boonnada
authors.initials: B
authors.lastname: Pamornpathomkul
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Theerasak
authors.initials: T
authors.lastname: Rojanarata
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Praneet
authors.initials: P
authors.lastname: Opanasopit
authors.affiliation: Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, Thailand.
authors.forename: Tanasait
authors.initials: T
authors.lastname: Ngawhirunpat
mesh_terms: D000818:Animals; D019793:Fluorescein / Q000737:chemistry / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D012867:Skin / Q000737:chemistry* / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects*; D013552:Swine
chemical_list: D005456:Fluorescent Dyes; D008081:Liposomes; D019793:Fluorescein
keywords: confocal laser scanning microscopy; mechanism of enhanced skin penetration; transmission electron microscopy; ultradeformable liposomes
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