Microbicidal Polymer Nanoparticles Containing Clotrimazole for Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) alters the innate cervicovaginal immunity, which provides an important barrier against viruses and other infections. The incidence of this disease has not decreased in the last 30 years, so effective treatments are still needed. Nanoparticles (NPs) of cellulose acetate phthalate (CAP) and clotrimazole (CLZ) were prepared by the emulsification-diffusion method. NPs were characterized using dynamic light scattering, atomic force microscopy and differential scanning calorimetry; their release profile was determined by the dialysis bag technique and mucoadhesion was evaluated with the mucin-particle method. The growth inhibition study of Candida albicans was carried out using the plate counting technique. Finally, accelerated physical stability tests of NPs were carried out, both in water and in SVF. The CAP-CLZ NPs had an average diameter of 273.4 nm, a PDI of 0.284, smooth surfaces and spherical shapes. In vitro release of CLZ from the CAP NPs was categorized with the Weibull model as a matrix system in which initial release was rapid and subsequently sustained. The inhibition of C. albicans growth by the CAP-CLZ NPs was greater than that of free CLZ, and the CAP-only NPs had a microbicidal effect on C. albicans. The NPs showed poor mucoadhesiveness, which could lead to studies of their mucopenetration capacities. An accelerated physical stability test revealed the erosion of CAP in aqueous media. A nanoparticulate system was developed and provided sustained release of CLZ, and it combined an antifungal agent with a microbial polymer that exhibited antifungal activity against C. albicans.

Alkylglycerol Derivatives, a New Class of Skin Penetration Modulators.

The absorption modulating activity of two alkylglycerol derivatives (batyl and chimyl alcohol) on skin barrier properties was evaluated. Biophysical tests such as transepidermal water loss (TEWL) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, as well as in vitro skin permeation studies, were performed in order to determine the effect of these compounds as chemical absorption modulators. Four drugs were used as models: three NSAIDS (diclofenac, naproxen, and piroxicam) and glycyrrhizic acid. The results showed that treatment of the skin with alkylglycerols caused (i) a reduction on the amount of drug permeated; (ii) a reduction in TEWL; and (iii) changes in the ATR-FTIR peaks of stratum corneum lipids, indicative of a more ordered structure. All of these findings confirm that alkyl glycerols have an absorption retarding effect on the drugs tested. Such effects are expected to give rise to important applications in the pharmaceutical and cosmetic sectors, in cases where it is desirable for the drug to remain in the superficial layers of the skin to achieve a local effect.

Preparation and characterization of solid lipid nanoparticles containing cyclosporine by the emulsification-diffusion method.

Solid lipid nanoparticles (SLNs) have been used for carrying different therapeutic agents because they improve absorption and bioavailability. The aim of the study was to prepare lipidic nanoparticles containing cyclosporine (CyA) by the emulsification-diffusion method and to study their physicochemical stability. Glyceryl behenate (Compritol(®) ATO 888) and lauroyl macrogolglycerides (Gelucire(®) 44/14) were used as carrier materials. Nanoparticles with good stability were obtained with Gelucire(®), while it was difficult to obtain stable systems with Compritol(®). Systems with Gelucire(®) were characterized by particle size, Z-potential, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), entrapment efficiency and in vitro release. Particle size and Z-potential were evaluated for at least three months. With a high CyA content (≥60 mg) in Gelucire(®) SLNs, variations in size were greater and particle size also increased over time in all batches; this effect may have been caused by a probable expulsion of the drug due to the lipid's partial rearrangement. While the Z-potential decreased 10 mV after three months, this effect may be explained by the superficial properties of the drug that make the molecules to be preferably oriented at the solid-liquid interface, causing a change in the net charge of the particle. SEM confirmed size and shape of the nanoparticles. DSC studies evidenced that CyA affects the lipid structure by a mechanism still unknown. The entrapment efficiency was higher than 92%, and CyA release from SLNs was relatively fast (99.60% in 45 min).

Silica xerogels as pharmaceutical drug carriers.

This review focuses on silica xerogels obtained by the sol-gel method and their application as drug delivery systems. SiO(2) xerogels are potential biomaterials to be used as matrix materials for the extended and controlled release of different kinds of biologically active agents administered by various routes. The article includes some representative examples that describe the encapsulation of bioactive molecules and model compounds inside a silica matrix produced by the conventional sol-gel method or by ultrasound hydrolysis. The drug release rate from xerogels could be modified by adjusting several parameters, such as the type of precursor, the concentration of the catalyst and drying temperature. In vitro and in vivo studies have shown the efficacy and biodegradability of these composites. The potential application of silica xerogels as drug carrier systems is critically analyzed and discussed.

Evaluation of SiO2 sonogels, prepared by a new catalyst-free method, as drug delivery system.

Recently, we reported on the synthesis of catalyst-free SiO(2) sonogels prepared by the sonication of a neutral distilled water/ tetraethyl ortosilicate mixture. The purpose of the present study was to evaluate the feasibility of using these sonogels as pharmaceutical delivery systems. A certified color additive (sunset yellow, SY) was used as a model compound for the release experiments. Different amounts of dye were incorporated into the gels before drying. Sonogels were characterized by scanning electron microscopy and differential scanning calorimetry. The effect of three drying temperatures (25 degrees C, 40 degrees C and 80 degrees C) and two mean grain sizes (1125 and 630 microm) on release behavior was analyzed. The analysis of variance showed no significant differences between the Higuchi's constants (K(H)) obtained for SY-loaded sonogels dried at 80 degrees C with different SY loads, irrespective of the mean grain size. In contrast, for SY-loaded sonogels dried at 40 degrees C, differences were found between sonogels loaded with 2.7, 7.7, 12.2, and 18.2% of SY, and no significant differences were detected between the mean grain sizes analyzed. Considering that the preparation of sonogels by the catalyst-free method allows an easy encapsulation, sonogels may offer an interesting alternative for drug release in the pharmaceutical field.