diflucortolone and Edema

The objective of this study was to prepare a suitable formulation for dermal delivery of diflucortolone valerate (DFV) that would maintain the localization in skin layers without any penetration and to optimize efficiency of DFV. Drug-loaded lecithin/chitosan nanoparticles with high entrapment efficiency (86.8%), were successfully prepared by ionic interaction technique. Sustained release of DFV was achieved without any initial burst release. Nanoparticles were also incorporated into chitosan gel at different ratios for preparing a more suitable formulation for topical drug delivery with adequate viscosity. In ex-vivo permeation studies, nanoparticles increased the accumulation of DFV especially in the stratum corneum + epidermis of rat skin without any significant permeation. Retention of DFV from nanoparticle in chitosan gel formulation (0.01%) was twofold higher than commercial cream, although it contained ten times less DFV. Nanoparticles in gel formulations produced significantly higher edema inhibition in rats compared with commercial cream in in-vivo studies. Skin blanching assay using a chromameter showed vasoconstriction similar to that of the commercial product. There were no barrier function changes upon application of nanoparticles. In-vitro and in-vivo results demonstrated that lecithin/chitosan nanoparticles in chitosan gel may be a promising carrier for dermal delivery of DFV in various skin disorders.

Topics: Administration, Cutaneous; Animals; Anti-Inflammatory Agents; Chitosan; Diflucortolone; Drug Carriers; Edema; Gels; Lecithins; Male; Mechanical Phenomena; Nanoparticles; Particle Size; Rats; Rats, Wistar; Skin; Skin Absorption; Vasoconstriction

The local anti-inflammatory activity and systemic side effects of NM-135 (6alpha,9-difluoro-11beta-hydroxy-16alpha-methyl-21[[2 ,3,4,6-tetrakis-O-(4-methylbenzoyl)-beta-D-glucopyranosyl]oxy]-pregna-1, 4-diene-3,20-dione) in croton oil-induced granuloma pouches and ear edema in rats were studied. The local anti-inflammatory activity of NM-135 was stronger than that of betamethasone 17-valerate (BV). As to systemic side effects, BV and diflucortolon valerate (DFV) caused thymolysis at the doses required for the anti-inflammatory activity. In contrast, no clear systemic side effect was observed in rats administered NM-135 at the dose producing the anti-inflammatory activity. These results suggest that NM-135 is a drug exhibiting a high degree of dissociation between the local anti-inflammatory activity and systemic side effects.

Topics: Animals; Anti-Inflammatory Agents; Atrophy; Betamethasone Valerate; Croton Oil; Diflucortolone; Disease Models, Animal; Dose-Response Relationship, Drug; Ear; Edema; Exudates and Transudates; Glucocorticoids; Granuloma; Inflammation; Male; Organ Size; Pregnanediones; Prodrugs; Rats; Rats, Sprague-Dawley; Thymus Gland

To establish a reliable laboratory assay for quantitating topical anti-inflammatory efficacy, the method of Tonelli et al was modified by employing felt fixed forceps, felt and sharp punch in Wistar rats. Croton oil, applied topically to the rat ear, elicited an acute phlogistic response which was maximal 6 hr after the application. The phlogistic response elicited by a single topical application of croton oil (1, 2, 5 and 10%) was increased in a dose-dependent manner, and croton oil, 5%, induced 63.2% increase of ear weight and was the optimal concentration for the experiment. Using this procedure, the antiphlogistic potencies of two corticoids were assayed under conditions of a blind test. ED50 of betamethasone valerate and diflucortolone valerate was 0.26 mg/ml and 0.0097 mg/ml, respectively, in Wistar rats, and 0.86 mg/ml and 0.016 mg/ml in Sprague Dawley rats, suggesting that diflucortolone valerate has an antiphlogistic potency of 27-56 relative to that seen with betamethasone valerate with minor differences in the strain of the rat. Our method should prove to be a useful assay for rapidly quantitating antiphlogistic activities of topically applied corticoids.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Betamethasone; Biological Assay; Croton Oil; Diflucortolone; Dose-Response Relationship, Drug; Double-Blind Method; Ear; Edema; Male; Rats; Time Factors