Comparison of Liposome-Encapsulated Acyclovir with Acyclovir Ointment: Ocular Pharmacokinetics in Rabbits

Abstract

A positively charged liposomal formulation for topical administration of acyclovir (ACV) was investigated in comparison with a commercial ACV ointment, by determining the pharmacokinetic profile of the drug in the aqueous humor of rabbits after topical administration. The ointment was tested at two different strengths: undiluted (3.0%) and diluted to the same ACV concentration as the liposomal vehicle (0.12%). A liquid formulation containing ACV plus "empty" liposomes and an isotonic aqueous ACV solution were also tested. The applied ACV dose was 0.18 mg, except for the full-strength (3.0%) ointment, in which case it was 1.5 mg. The ACV liposomal dispersion (LIPO-ACV) produced a significantly higher drug concentration profile in the aqueous with respect the three reference formulations containing the same ACV concentration, and showed a 90-minute plateau. The aqueous humor ACV concentration maintained by LIPO-ACV during the plateau was in the upper range of the ID(50)s (0.01 to 0.7 microg/mL) reported for Herpes simplex type 1. In spite of the much higher dose (1.5 versus 0.18 mg), the area under curve (AUC) produced by the full-strength 3.0% ointment was only 1.6 times greater than that corresponding to the liposomal vehicle. In vitro release tests through a cellophane membrane substantiated the concept that positively charged liposomal formulations owe their efficacy to interactions with the positively charged corneal epithelium.

Controlled Release of Acyclovir Through Bioengineered Corneal Implants with Silica Nanoparticle Carriers~!2009-08-29~!2010-01-05~!2010-03-18~!

“…PECA nanospheres in topical applications [36], Eudragit microparticles [26], or liposomes) [19]) have been successful in extending drug release time and therefore availability. However, in vivo applications are still proble-matic as both drugs and their carriers are rapidly cleared from the ocular surface by tearing and blinking.…”

“…However, in vivo applications are still proble-matic as both drugs and their carriers are rapidly cleared from the ocular surface by tearing and blinking. Hence, incorporation of carriers into a retentive ophthalmic ointment [19] or into contact lenses [22] have been proposed as means of extending drug availability to the ocular surface. However, to remedy HSV-induced vision loss, instead of treating the cornea with drugs and performing allograft surgery as two separate modalities, both with limited success rates, our results indicate that it would be possible to incorporate the drug/carrier directly into biosynthetic substitutes of human donor corneas [11,12], to allow for the drug to be released after implantation to prevent viral re-activation and re-infection.…”

“…This delivery method demonstrates low efficacy, due to poor drug solubility and lack of penetration to the target sites [14,17,18]. Topical delivery of ACV through colloidal systems such as encapsulated nanoparticles, microparticles, and lipsomes, has improved the delivery of this drug to some degree [19][20][21]. Efficacy is still limited as the product is quickly discharged from the eye (i.e.…”

Applications of Nanobiotechnology in Ophthalmology – Part I

“…In 2000, Law et al [50] demonstrated improved corneal deposition with the cationic acyclovir-containing liposomes, compared to either the anionic or unencapsulated modalities. The liposome-encapsulated acyclovir was demonstrated to have better delivery than the commercial acyclovir ointment, at different concentrations, in rabbit model and in vitro release tests [51] . The authors postulated that the nonspecific ionic interactions increase the precorneal residence time by forming a more intimate and complete coating of the negatively charged corneal surface.…”

Nonpolymeric nanoassemblies for ocular administration of acyclovir: Pharmacokinetic evaluation in rabbits

“…The osmolality of the preparation was adjusted to physiological values with sodium chloride, and pH was 6.5 [25].…”