Lau, Kent G.; (2002) Formulation of novel double-chain lipid vesicles. Doctoral thesis (Ph.D.), University College London.

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Abstract

Ceramide, the primary constituent in mammalian stratum corneum (SC), is essential for maintaining water-barrier properties of the skin. SC lipid extracts can form liposomes. These vesicles can fuse with the outermost layers of SC when applied in vitro. SC lipid liposomes loaded with skin-active solutes may be able to deliver hydrophilic therapeutic agents into SC and beyond. In this project, a series of novel double-chain lipids (DCLs) were investigated for their potential to associate into liposomes. These DCLs are derivatives of alkenyl succinic anhydride (ASA) and exhibit acyl chains of C16 to C18 in length. They mimic the spatial geometry of native ceramides and were pre-selected for their intrinsic ability to improve moisture retention in damaged skin. Formation of DCL vesicles was revealed by fluorescence of 5,6-carboxyfluorescein (CF) encapsulated in their aqueous interiors. Successful novel DCL candidates were incorporated into phospholipid-based and SC lipid-extract multi-lamellar vesicles (MLVs) and dehydrated-rehydrated vesicles (DRVs). Entrapment efficiency of CF, [14C]sucrose and [125I]albumin was evaluated. Vesicle size and surface charge were characterized. DRVs incorporating novel DCLs were loaded with [14C]sucrose and Arlamol-GEO, a low molecular weight, hydrophilic, skin-active solute. They were stored at room temperature and solute retention was studied over several weeks. Initially, solute leakage from DCL-DRVs was much greater than control phospholipid- based DRVs and the initial rate of leakage significantly influenced the final retention value.

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