Computer simulation of convective and diffusive transport of controlled-release drugs in the vitreous humor

Matthew S. Stay, Jing Xu, Theodore W. Randolph, Victor H. Barocas

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

Purpose. Biodistribution of drugs in the eye is central to the efficacy of pharmaceutical ocular therapies. Of particular interest to us is the effect of intravitreal transport on distribution of controlled-released drugs within the vitreous. Methods. A computer model was developed to describe the three-dimensional convective-diffusive transport of drug released from an intravitreal controlled release source. Unlike previous studies, this work includes flow of aqueous from the anterior to the posterior of the vitreous. The release profile was based on in vitro release of gentamicin from poly(L-lactic acid) microspheres into vitreous. Results. For small drugs, convection plays a small role, but for large (slower diffusing) drugs, convection becomes more important. For the cases studied, the predicted ratio of drug reaching the retina to drug cleared by the aqueous humor was 2.4 for a small molecule but 13 for a large molecule. Transport in neonatal mouse eye. in contrast, was dominated by diffusion, and the ratio decreased to 0.39. Conclusions. The interaction among convection, diffusion, and geometry causes significant differences in biodistribution between large and small molecules or across species. These differences should be considered in the design of delivery strategies or animal studies.

Original languageEnglish (US)
Pages (from-to)96-102
Number of pages7
JournalPharmaceutical research
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Biodistribution
  • Ocular drug delivery
  • Sustained release

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