Comparison of the ocular distribution of a model oligonucleotide after topical instillation in rabbits of conventional and new dosage forms

The distribution of a model 16-mer oligothymidylate (pdT16) in several ocul ar tissues (cornea. conjunctiva. scleral iris, lens, aqueous and vitreous h umors) was determined after instillation in the eye of various dosage forms in a rabbit model. Radiolabelled pdT16 was applied as a simple solution. a 27% poloxamer 407 gel. a suspension of liposomes or liposomes dispersed wi thin a 27% poloxamer 407 gel. pdT16 concentrations were measured in the tis sues and fluids by radioactivity counting at time intervals of 10 min, 2 h and 24 h. When the pdT16 solution was used. the highest concentrations were observed in the conjunctiva and the cornea. while a substantial amount of drug was also present in the sclera. Low concentrations were measured in th e iris. Using the same treatment protocol, the two liposomal formulations ( liposomes suspension or liposomes dispersed within the poloxamer gel) deliv ered lon amounts of pdT16 to all ocular tissues, and particularly to the co njunctiva and the cornea. The poloxamer gel provided higher tissue concentr ations of pdT16 than liposomes but lower than those observed with the solut ion except 10 min after administration in the iris where the amounts of pdT 16 were higher when administered under the gel form. These findings indicat e that liposomal forms may not be considered useful delivery systems for to pical administration of oligonucleotides in superficial ocular diseases.