Novel Pemulen/Pullulan blended hydrogel containing clotrimazole-loaded cationic nanocapsules: Evaluation of mucoadhesion and vaginal permeation.

In this work, hydrogels containing clotrimazole-loaded nanocapsules were developed through the innovative association of two mucoadhesive polymers: Pemulen® TR1 and Pullulan. Furthermore, the hydrogels macroscopic characteristics, pH and spreadability were evaluated. The formulations showed homogeneous appearance and pH compatible with vaginal application (around 5.0). Similar spreadability profiles were found in hydrogels containing clotrimazole-loaded nanocapsules and in the free drug as well. Hydrogels were evaluated considering their mucoadhesive potential by the falling liquid film method and the permeation/penetration capacity through cow vaginal mucosa in Franz cell. The results showed that the concentration of 3% Pullulan was important to increase the adhesive strength on the layer used (mucin gel or animal mucosa). The results of the permeation/penetration study showed that the hydrogel containing clotrimazole-loaded nanocapsules remained on the vaginal mucosa surface, what is ideal for the treatment of superficial vaginal infections. This way, the Pemulen/Pullulan blended hydrogel is a promising alternative for the treatment of vulvovaginal candidiasis.

Association of Borage Oil and Betamethasone Dipropionate in Lipid-Core Nanocapsules: Characterization, Photostability and In Vitro Irritation Test.

The association of vegetable products to nanostructured systems has attracted the attention of researchers due to several advantages, such as drug photoprotection, as well as the improvement of the pharmacological and therapeutic activities because of synergistic action, which can provide their topical application. In this work, lipid-core nanocapsules containing borage oil as oil core and betamethasone dipropionate were developed, and nanocapsules without the drug were prepared for comparison. The suspensions were characterized in relation to mean particle size, zeta potential, pH, drug content, and encapsulation efficiency. A photodegradation study was carried out and the in vitro release profile as well as the irritation potential of the drug after nanoencapsulation were also evaluated. In addition, the antiproliferative activity of the free borage oil as well as loaded in nanocapsules was studied. Lipid-core nanocapsules showed nanometric mean size (185-210 nm); polydispersity index below 0.10; negative zeta potential and pH slightly acid (6.0-6.2). Moreover, the drug content was close to theoretical concentration (0.50 +/- 0.03 mg/ml of betamethasone), and the encapsulation efficiency was approximately 100%. The study of the antiproliferative activity of borage oil showed ability to reduce cell growth of Allium cepa. The nanoencapsulation of betamethasone dipropionate provided greater protection against UVC light and decreased the irritation potential of the drug. The release profile of betamethasone dipropionate from nanocapsules followed monoexponential model.

Dithranol-loaded lipid-core nanocapsules improve the photostability and reduce the in vitro irritation potential of this drug.

Dithranol is a very effective drug for the topical treatment of psoriasis. However, it has some adverse effects such as irritation and stain in the skin that make its application and patient adherence to treatment difficult. The aims of this work were to prepare and characterize dithranol-loaded nanocapsules as well as to evaluate the photostability and the irritation potential of these nanocarriers. Lipid-core nanocapsules containing dithranol (0.5 mg/mL) were prepared by interfacial deposition of preformed polymer. EDTA (0.05%) or ascorbic acid (0.02%) was used as antioxidants. After preparation, dithranol-loaded lipid-core nanocapsules showed satisfactory characteristics: drug content close to the theoretical concentration, encapsulation efficiency of about 100%, nanometric mean size (230-250 nm), polydispersity index below 0.25, negative zeta potential, and pH values from 4.3 to 5.6. In the photodegradation study against UVA light, we observed a higher stability of the dithranol-loaded lipid-core nanocapsules comparing to the solution containing the free drug (half-life times around 4 and 1h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing EDTA, respectively; half-life times around 17 and 7h for the dithranol-loaded lipid-core nanocapsules and free drug solution containing ascorbic acid, respectively). Irritation test by HET-CAM method was conducted to evaluate the safety of the formulations. From the results it was found that the nanoencapsulation of the drug decreased its toxicity compared to the effects observed for the free drug.