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

A photosensitive drug (riboflavin) was entrapped as such or in the for m of beta- or gamma-cyclodextrin complexes into the aqueous phase of m ultilamellar dehydration-rehydration vesicles (DRV liposomes) made of equimolar egg phosphatidylcholine or dipalmitoylphosphatidylcholine an d 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 liposo mes together with riboflavin). In some experiments, lipid-soluble abso rbers were supplemented with the antioxidant beta-carotene. Entrapment values for free (41-47%) and complexed (19-23%) riboflavin were estim ated fluorimetrically with additional data from NMR studies confirming that the complexes were entrapped as intact entities. Entrapment valu es 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 de rivative of their UV spectra to circumvent interference from overlappi ng absorption spectra of the other agents, when present. A number of c onditions of entrapment were found to reduce values, for instance co-e ntrapment of sulisobenzone together with the vitamin in the case of ri boflavin and, for all other materials, the absence (or reduced content ) of cholesterol in DRV or certain variations in their manufacture. Ex posure of a variety of riboflavin-containing DRV preparations to UV li ght revealed optimal protection with a formulation containing the gamm a-cyclodextrin complex of the vitamin, all three lipid-soluble light a bsorbers and beta-carotene, increasing the half-life of riboflavin 266 -fold. Results suggest that liposome-based multicomponent systems coul d be developed for the protection of photolabile agents in therapeutic s and other uses.