Vitamin A palmitate and aciclovir biodegradable microspheres for intraocular sustained release

Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain.
International Journal of Pharmaceutics (Impact Factor: 3.65). 01/2007; 326(1-2):100-6. DOI: 10.1016/j.ijpharm.2006.07.010
Source: PubMed


The aim of this study was to obtain a prolonged release of Vitamin A palmitate (RAP) and aciclovir from biodegradable microspheres for intraocular administration with an antiviral action and to be capable of preventing the inherent risks of intravitreal administration. The RAP effect on the microsphere characteristics was also studied. Poly(D,L-lactic-co-glycolic) acid microspheres were prepared by the solvent evaporation method. Different quantities of aciclovir (40-80 mg) and RAP (10-80 mg) were added to the internal phase of the emulsion. Microspheres were analysed by scanning electron microscopy, which revealed a spherical surface and a porous structure, and granulometric analysis that showed an adequate particle size for intraocular administration. The aciclovir loading efficiency increased when Vitamin A palmitate was added. Differential scanning calorimetry detected no differences in the polymer glass transition temperature and the aciclovir melting endotherm in all formulations. The release of aciclovir during the first days of the in vitro assay was improved with respect to microspheres without RAP. The microspheres showed a constant release of aciclovir and RAP for 49 days. Best results were obtained for microspheres prepared with 40 mg aciclovir, 80 mg RAP and 400mg polymer. A dose of 4.74 mg of microspheres would be therapeutic for the herpes simplex and Epstein-Barr viruses' treatment in an animal model and would reduce the intravitreal adverse effects. The injectability of a suspension of microspheres in isotonic saline solution resulted appropriate for its injection through a 27 G needle.

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    ABSTRACT: Disorders affecting the posterior segment of the eye are one of the major causes of blindness in western countries. Treatments of these pathologies often require multiple intravitreal injections to achieve effective concentrations in the vitreous cavity. However, repeated injections are poorly tolerated and are frequently associated with cataract formation, retinal detachment, and endophthalmitis. Furthermore, the risk of adverse effects increases with the frequency of intravitreal administration. Injectable microparticles offer a good alternative to multiple injections because they can be administered as conventional intraocular formulations. Among them, microspheres prepared from biodegradable polymers such as poly(lactic) (PLA) acid and poly(lactic-co- glycolic)acid (PLGA) have the advantage of disappearing from the site of administration once the active substance has been delivered. This work describes relevant in vitro and in vivo parameters and variables related to the intravitreal administration of PLA and PLGA microspheres for the treatment of diseases affecting the posterior segment.
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