NOVEL LIPOSOME-BASED MULTICOMPONENT SYSTEMS FOR THE PROTECTION OF PHOTOLABILE AGENTS

A photosensitive drug (riboflavin) was entrapped as such or in the form of beta- or gamma-cyclodextrin complexes into the aqueous phase of multilamellar dehydration-rehydration vesicles (DRV liposomes) made of equimolar egg phosphatidylcholine or dipalmitoylphosphatidylcholine and cholesterol. Riboflavin-containing DRV were prepared in the absence or presence of one or more of the lipid-soluble UV absorbers oil red O, oxybenzone and dioxybenzone (entrapped into the lipid phase) and the water-soluble sulisobenzone (entrapped in the aqueous phase of liposomes together with riboflavin). In some experiments, lipid-soluble absorbers were supplemented with the antioxidant beta-carotene. Entrapment values for free (41-47%) and complexed (19-23%) riboflavin were estimated fluorimetrically with additional data from NMR studies confirming that the complexes were entrapped as intact entities. Entrapment values for each of the UV light lipid-soluble absorbers (79-98%) and beta-carotene (78 and 88%) were estimated by the use of the second-order derivative of their UV spectra to circumvent interference from overlapping absorption spectra of the other agents, when present. A number of conditions of entrapment were found to reduce values, for instance co-entrapment of sulisobenzone together with the vitamin in the case of riboflavin and, for all other materials, the absence (or reduced content) of cholesterol in DRV or certain variations in their manufacture. Exposure of a variety of riboflavin-containing DRV preparations to UV light revealed optimal protection with a formulation containing the gamma-cyclodextrin complex of the vitamin, all three lipid-soluble light absorbers and beta-carotene, increasing the half-life of riboflavin 266-fold. Results suggest that liposome-based multicomponent systems could be developed for the protection of photolabile agents in therapeutics and other uses.