In vitro and in vivo topical delivery studies of tretinoin-loaded ultradeformable vesicles

• UDV contributed to a sustained and controlled tretinoin release.
• Tretinoin–UDV was not toxic under in vitro and in vivo conditions.
• Tretinoin–UDV can be considered as a promising delivery system for topical delivery.

IntroductionUltradeformable vesicles are highly promising tools to enhance the percutaneous transport of different drugs such as tretinoin across the skin barrier and also to increase the formulation stability at absorption site and reduce the drug induced irritation.MethodsTopical delivery of tretinoin-loaded ultradeformable vesicles (tretinoin–UDV) was evaluated concerning different studies, such as: the release and permeation profiles (tape stripping); skin penetration (fluorescence analysis); induced electrical changes in skin barrier properties; cytotoxicity (Trypan Blue assay) and skin irritation in in vivo conditions (Draize test). The novel formulation performance was also compared to a commercial tretinoin formulation regarding in vivo studies.ResultsIt was obtained a sustained and controlled drug release, as expected for UDV formulation. In addition, a dermal delivery was observed regarding the permeation study since it was not detected any drug amount in the receptor phase after 24 h. Nile Red–UDV stained intensively mostly in the stratum corneum, corroborating the tape stripping results. Tretinoin–UDV decreased skin resistance, suggesting its ability to induce skin barrier disruption. Finally, the formulation vehicle (empty UDV) and tretinoin–UDV were not toxic under in vitro and in vivo conditions, at least, at 5 × 10−3 mg/mL and 0.5 mg/mL of tretinoin, respectively.ConclusionTretinoin−UDV is a promising delivery system for tretinoin dermal delivery without promoting skin irritation (unlike other commercial formulations), which is quite advantageous for therapeutic purpose.

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