IMPREGNATION OF COLLAGEN CORNEAL SHIELDS WITH LIPOSOMES - UPTAKE AND RELEASE OF HYDROPHILIC AND LIPOPHILIC MARKER SUBSTANCES

Purpose. Liposomes and collagen corneal shields (CCS) have been used a s ophthalmic drug delivery devices. With regard to a possibly combined application, we studied the effects of surface charge and bilayer flu idity of liposomes on their uptake and release by CCS. Methods. 12-hou rs-CCS were soaked in large unilamellar liposomes, which had been labe lled with 4,5-carboxyfluorescein (CF) and N-(lissamine rhodamine B sul fonyl)-diacylphosphatidylethanolamine (PE-RhB) in the aqueous space an d in the liposome bilayer, respectively. Released fluorophores were de termined fluorometrically in the elution buffer at intervals from 1 to 240 min after immersion.Results. The CF concentration in the CCS soak ed in a CF solution was two to seven times higher than immersion in th e liposome suspensions. Among those, the negatively charged, cholester ol-containing preparation led to the highest CF concentration in the C CS. The PE-RhB concentration was highest after soaking the CCS in neut ral, cholesterol-free liposomes. All types of liposomes were found ins ide the CCS by freeze fracture electron microscopy. The release kineti cs data indicate a first order release. More than 90% of CF was releas ed by the CCS within the first 30 min. This was equal after soaking th e CCS in the CF solution or in liposomes. With DOPC-liposomes, the max imal release was already attained after 10 min. In general, the differ ences in the release kinetics of both hydrophilic and lipophilic marke rs, obtained by the various liposome types were small. Conclusions. Ou r results indicate that surface charge and bilayer fluidity are of min or importance for the interaction with collagen corneal shields. Howev er, since the release kinetics of a liposome-encapsulated hydrophilic or lipophilic substance are similar to the release of a non-encapsulat ed drug, the combination of liposomes with collagen shields may be use ful mainly with respect to the encapsulation of drugs which do not pen etrate the ocular surface as well as to prolong corneal contact time o f the liposomes.