Ca2+ Efflux from Temperature Sensitive Liposomes and In Situ Formation of Metal Cholate Liposome Gels: Basic Studies and Potentials for Sustained Site-Specific Drug Delivery

Abstract

Liposomes or vesicles are biomimetic close containers for the delivery of drugs at the local site for an extended period of time. On the other hand hydrogels which are three-dimensional hydrophilic matrices are another class of popular materials for sustained release. Such hybrids combine the features of liposomes and polymer to ensure a sustained local drug delivery. In the present work a novel liposome/hydrogel soft assembly is explored which may be potentially useful for drug delivery applications. We report thermally triggered release of Ca⁺² from temperature sensitive liposomal  compartments constituted as 90 mol% DPPC and 10 mol% DMPC to induce rapid gelation of a solution of calcium cholate and AgNO₃ (extravesicular precursor fluid). Calcium chloride loaded liposomes were prepared using the lipid film rehydration method. The formation of unilamellar bilayer were supported by the fluorometric studies using a compatible and labeled fluoropore (NBD-PS). Hydrogels were obtained by mixing Ca⁺² loaded liposome with extravesicular precursor fluid and incubating the content at 37^oC. The concentration of the cholate during gelation was sublytic in order to avoid vesicle solubilization. The integrity of liposomes within the hydrogels were preserved during gelation as confirmed by transmission electron microscopy (TEM). The presence of low concentration of cholate (for example 0.05 mM) also permitted spectrophotometric monitoring of Ca⁺² efflux for Ca-vesicles employing calcium sensitive dye, Arsenazo III.  We expect that this simple experiment may also be useful for developing implantable as well as rapidly gelling injectable biomaterials for site-specific drug delivery. The present work is also significant as the antimicrobial properties of hydrogels containing silver has been widely recognized for its therapeutic profile.  

Keywords: Liposome, triggered release, metal cholate liposome gel, site-specific delivery.