Optimization of topical cidofovir penetration using microparticles

Abstract

Cidofovir is a new class of antiviral agent with potent in vitro and in vivo activity against a broad spectrum of herpes viruses. The aim of this work was to obtain a prolonged therapeutic effect of cidofovir in the basal epidermis after its topical application. For this purpose, PLGA microparticles were prepared by solvent evaporation and spray-drying methods. Microparticles prepared by spray-drying showed a encapsulation efficiency of 80%.Conversely, for all the microspheres prepared by the W/O/W solvent evaporation method the encapsulation efficiency was low. Also, microparticles prepared by spray-drying showed a higher burst release. Skin penetration and distribution experiments were carried out with cidofovir-loaded microparticles prepared by spray-drying, since these carriers presented the best characteristics in terms of size and encapsulation efficiency. A cidofovir solution in 0.2% PVA served for comparison. Penetration experiments were carried out in Franz type diffusion cells with an available diffusion area of 1.76 cm 2 , using porcine skin. The results obtainedshowed that the amount of cidofovir penetrated, over a 24 h time period, was higher with the drug solution than with microparticles. Cidofovir distribution in porcine skin, after topical application of microparticles and drug solution for 24 h, was determined by horizontal slicing of the skin. The profiles obtained for the two formulations showed that the quantity of cidofovir retained in the skin decreased with the depth. Besides the amount of cidofovir found in the basal epidermis (120-150 μm) was much higher with microparticles than with the control solution. These data showed that cidofovir-loaded microparticles could improve cidofovir topical therapy since these vehicles increased drug retention in the basal epidermis and decreased its penetration through the skin.

Microparticulate Based Topical Delivery System of Clobetasol Propionate

“…It has been also shown that PLGA microparticles could be used to deliver acyclovir into the basal epidermis (19). Similar results were obtained in some studies which were carried out with different drugs for topical delivery, such as cidofovir (20) and urea (13).…”

In Vitro and In Vivo Evaluation of Hydroxyzine Hydrochloride Microsponges for Topical Delivery

“…A previous study on the topical antiviral effect of cidofovirloaded microparticles (36) suggested the passage of the drug at higher concentrations to the first skin layers to an occlusive effect exerted by microparticles. That effect produced a film on the skin surface which reduced the transepidermal water loss and favored drug penetration into the skin.…”

Preparation and Evaluation of Tubular Micelles of Pluronic Lecithin Organogel for Transdermal Delivery of Sumatriptan

“…Various other systems have also been developed for delivery of active principles through the skin such as acyclovir-loaded poly(lactic-co-glycolic acid) (PLGA) topical microparticles (37)(38)(39), microsponges for topical delivery mupirocin (40), biodegradable PLGA microparticles in o/w and w/o cream (41), block copolymer nanoparticles (42), biodegradable nanoparticles (43), and PLA nanoparticles (44). Further, the strategies for vectorization of drug across the skin have been extended to polymeric gels like pluronic lecithin organogels (45), bioadhesive gels, etc.…”