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J Drug Target. 1998;6(4):309-13.

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

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1
Laboratoire de Physico-Chimie, Pharmacotechnie, Biopharmacie, URA CNRS 1218, Faculté de Pharmacie, Châtenay-Malabry, France.

Abstract

The distribution of a model 16-mer oligothymidylate (pdT16) in several ocular tissues (cornea, conjunctiva, sclera, iris, lens, aqueous and vitreous humors) 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 within a 27% poloxamer 407 gel. pdT16 concentrations were measured in the tissues and fluids by radioactivity counting at time intervals of 10 min, 2 h and 24 h. When the pdT 16 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 the iris. Using the same treatment protocol, the two liposomal formulations (liposomes suspension or liposomes dispersed within the poloxamer gel) delivered low amounts of pdT16 to all ocular tissues, and particularly to the conjunctiva and the cornea. The poloxamer gel provided higher tissue concentrations of pdT16 than liposomes but lower than those observed with the solution except 10 min after administration in the iris where the amounts of pdT16 were higher when administered under the gel form. These findings indicate that liposomal forms may not be considered useful delivery systems for topical administration of oligonucleotides in superficial ocular diseases.

PMID:
9894698
DOI:
10.3109/10611869808996838
[Indexed for MEDLINE]
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