Vitamin A palmitate and aciclovir biodegradable microspheres for intraocular sustained release
ABSTRACT 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.
- SourceAvailable from: Linhua Zhang
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- "Intravitreal injections generally achieve improved drug absorption and diminish or prevent the adverse effects associated with systemic or topical treatment. However, many of the vitreoretinal diseases that intravitreal injections target are not controlled by a single injection, and the need for multiple injections is poorly tolerated and has inherent risks, such as endophthalmitis, cataract, retinal detachment, and vitreous hemorrhage.3,4 Moreover, the low therapeutic rate of some drugs used for the treatment of the posterior segment diseases can lead to toxic concentrations in the retina. "
ABSTRACT: The aim of the study was to investigate the tolerance and pharmacokinetics of dexamethasone (DEX)-loaded poly(lactic acid-co-glycolic acid) nanoparticles (DEX-NPs) in rabbits after intravitreal injection. The DEX-NPs were prepared and characterized in terms of morphology, particle size and size distribution, encapsulation efficiency, and in vitro release. Ophthalmic investigations were performed, including fundus observation and photography, intraocular pressure measurement, and B-scan ocular ultrasonography. There were no abnormalities up to 50 days after administration of DEX-NPs in rabbits. The DEX concentrations in plasma and the ocular tissues such as the cornea, aqueous humor, lens, iris, vitreous humor, and chorioretina were determined by high-pressure liquid chromatography. The DEX-NPs maintained a sustained release of DEX for about 50 days in vitreous and provided relatively constant DEX levels for more than 30 days with a mean concentration of 3.85 mg/L(-1). Based on the areas under the curve, the bioavailability of DEX in the experimental group was significantly higher than that in the control group injected with regular DEX. These results suggest that intravitreal injection of DEX-NPs lead to a sustained release of DEX with a high bioavailability, providing a basis for a novel approach to the treatment of posterior segment diseases.International Journal of Nanomedicine 09/2009; 4:175-83. · 4.38 Impact Factor
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ABSTRACT: This chapter discusses various types of dispersed systems, including applications of coarse and colloidal dispersions as pharmaceutical dosage and delivery systems. Applications of colloidal dispersions as controlled drug delivery systems are also discussed in this chapter.
- Journal of Drug Delivery Science and Technology 12/2008; 18(2):119-124. DOI:10.1016/S1773-2247(08)50019-0 · 1.09 Impact Factor