title: Glucocorticoid entrapment into lipid carriers--characterisation by parelectric spectroscopy and influence on dermal uptake.
abstract: Topical glucocorticoids such as betamethasone 17-valerate (BMV) and prednicarbate (PC) are an important therapeutic option in atopic eczema. To reduce the risk of dermal atrophy, we aimed at BMV incorporation into solid lipid nanoparticles (SLN) for epidermal targeting using various lipids and emulsifiers corresponding to previous work on PC. Cutaneous absorption into excised human skin was compared to the one with a cream. While Compritol-based particles increased BMV uptake about fourfold we failed, however, to obtain epidermal targeting. To obtain insight into the location of active substance relative to the carrier, we used the recently optimised method of parelectric spectroscopy (PS). In fact, we were able to study electric dipole movements in the broad field of a frequency span from 0.1 to 100 MHz demonstrating that glucocorticoids are attached to the particle surface but are not incorporated into the lipid matrix. With BMV, the loading capacity of the particle surface lies clearly below the usual concentration of 0.1% which is not the case with PC. An adequate association of drug and carrier is essential for epidermal targeting. Parelectric spectroscopy provides insight into the interaction between drug and lipidic carrier.
authors.affiliation: Department of Physics, Freie Universität Berlin, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Sivaramakrishnan
authors.forename: C
authors.initials: C
authors.lastname: Nakamura
authors.forename: W
authors.initials: W
authors.lastname: Mehnert
authors.forename: H C
authors.initials: HC
authors.lastname: Korting
authors.forename: K D
authors.initials: KD
authors.lastname: Kramer
authors.forename: M
authors.initials: M
authors.lastname: Schäfer-Korting
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004337:Drug Carriers / Q000032:analysis / Q000493:pharmacokinetics*; D005260:Female; D005938:Glucocorticoids / Q000032:analysis / Q000493:pharmacokinetics*; D006801:Humans; D008055:Lipids / Q000032:analysis / Q000493:pharmacokinetics*; D008875:Middle Aged; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*
chemical_list: D004337:Drug Carriers; D005938:Glucocorticoids; D008055:Lipids