Ocular disposition of nanoencapsulated acyclovir and ganciclovir via intravitreal injection in rabbit's eye

Abstract

Ganciclovir nanoparticles were prepared using biodegradable polymers to evaluate a possible treatment for cytomegalovirus (CMV) retinitis. Bovine serum albumin (BSA), polyethylcyanoacrylate (PEC), and chitosan were utilized as drug carriers. The three products were evaluated for drug-loading capacity, particle size, and drug release. Spherical nanoparticles ranging between 0.3 and 1.2 μm in diameter were obtained, with those of PEC being the smallest. Loading capacity was in the range of 62.5–66.9%. Drug release studies revealed decreasing release rates in the following order: BSA > PEC ≥ chitosan. PEC nanoparticles containing ganciclovir (measured spectrophotometrically) and radioactive acyclovir (measured by liquid scintillation) showed essentially the same release patterns. The PEC nanoparticles containing [3H]acyclovir and ganciclovir together were selected for in vivo drug level studies. Following an intravitreal injection in rabbit eyes, drug levels in different eye tissues were used to compare the nanoparticle dispersion with free drug solution. The PEC nanoparticle product showed a markedly higher concentration than that of the drug solution over the 10 days, especially in the vitreous and retina. Therapeutic levels were detected for up to 10 days following administration of the nanospheres. Some lens opacification and vitreous turbidity were associated with administration of the PEC nanoparticles.