Development of a nanotechnological hydrogel containing desonide nanocapsules in association with acai oil: design and in vivo evaluation.

Nanotechnological products have been used as strategies to optimize the therapy and minimize the side effects of topical corticoids. The objective of this study was to develop hydrogels by the addition of sclerotium gum to the suspensions of desonide-loaded açai oil-based nanocapsules and to study their biological effect using an animal model of acute skin inflammation. The hydrogels presented a pH compatible with topical application (4.4 to 5.0), nanometric mean diameter (131 to 165 nm), pseudoplastic behavior, and stability under room conditions during 30 days. The in vitro skin permeation/penetration study demonstrated that a higher amount of desonide (p < 0.05) was retained in the epidermis from the nanotechnological-hydrogels (0.33 to 0.36 µg.cm2) in comparison to the commercial gel cream (0.16 µg.cm2). In the dermis, the nanostructured hydrogels promoted a lower DES retention compared to the non-nanostructured formulations (p < 0.05). This result may indicate a smaller amount of drug reaching the bloodstream and, thus, fewer side effects can be expected. Concerning the anti-inflammatory effect, the developed hydrogels reduced both ear edema and inflammatory cell infiltration, showing an effect comparable to the commercially available formulation, which presents twice the drug concentration. The hydrogels developed may be considered a promising approach to treat dermatological disorders.

Genotoxic effects of Campomanesia xanthocarpa extracts on Allium cepa vegetal system.

UNLABELLED: CONTEXT. Campomanesia xanthocarpa Berg. (Myrtaceae), popularly known in Brazil as guabiroba, is a plant used as antidiarrheic, anti-inflammatory and antirheumatic agents, and in stomach and hepatic disorders. OBJECTIVE: The antiproliferative and genotoxic effects of aqueous extracts and essential oil of C. xanthocarpa were evaluated. MATERIALS AND METHODS: Cytotoxicity and genotoxicity of the aqueous extracts (6 and 30 mg/mL) and essential oil (0.25%, v/v) obtained from leaves of C. xanthocarpa were evaluated using the Allium cepa L. (Amaryllidaceae) assay. Mitotic index was calculated as the percentage of dividing cells of total cells observed; chromosome abnormalities were observed and counted during cell division. Additionally, the composition of the essential oil and the quantification of the main compounds of the extracts were determined by gas chromatography/mass spectrometry and high performance liquid chromatography coupled with diode array detector, respectively. RESULTS AND DISCUSSION: Aqueous extracts (6 and 30 mg/mL) led to a reduction of 67.7% and 34.1% of the mitotic index, respectively, whereas the treatment with essential oil caused a 48.2% reduction in the mitotic index, when compared with negative control. Chromosomal mutations were observed and included anaphase bridges, delay chromosome, break chromosome, as well as metaphase with disorganized chromosomal and binuclear cells. The main compounds of the essential oil were ß-caryophyllene (8.87%), viridiflorol (6.40%), spathulenol (5.16%), δ-cadinene (4.92%), linalool (4.46%) and α-cadinol (4.25%). Gallic acid (3.19%), chlorogenic acid (1.04%), quercetin (2.97%) and rutin (4.82%) were identified in an aqueous extract (30 mg/mL). CONCLUSION: Our results demonstrated that genotoxic and antiproliferative activities are present in C. xanthocarpa infusions using the in vivo onion root-tip cell test.

Desonide nanoencapsulation with açai oil as oil core: Physicochemical characterization, photostability study and in vitro phototoxicity evaluation.

This study aimed to develop Eudragit® RL 100 nanocapsules loaded with desonide (DES) using açai oil (AO) or medium chain triglycerides (MCT) as oil core. Pre-formulation study showed that AO and MCT are suitable for nanocapsules preparation. The nanocapsules prepared with AO and MCT presented mean particle size around 165 and 131 nm, respectively; polydispersity index values <0.20, positive zeta potential values, drug content close to the theoretical value (0.25 mg mL-1), and DES encapsulation efficiency around 81%, regardless of the oil core (AO or MCT). Considering the photoinstability reported to DES, photodegradation studies were performed. The UV-A (365 nm) and UV-C (254 nm) photodegradation studies revealed less DES degradation when associated to the nanocapsules containing AO in comparison to those with MCT. The in vitro release study showed a biphasic release profile for both nanocapsule suspensions: an initial burst effect followed by a prolonged DES release. In addition, the formulations were considered non-phototoxic at 0.5 mg mL-1 when tested on 3 T3 murine fibroblasts and HaCaT human keratinocytes using the MTT and NRU viability assays. The irritant potential of the prepared nanocapsules and DES in free form were evaluated by HET-CAM method. All formulations were classified as slightly irritant, including the non-associate DES. In conclusion, the nanocapsule formulations developed in this study may be promising for therapeutic applications.

Novel Pullulan-Eudragit® S100 blend microparticles for oral delivery of risedronate: formulation, in vitro evaluation and tableting of blend microparticles.

Polymer blends have been considered a promising strategy to tailor drug release. In order to achieve gastroresistance and controlled release, Pullulan, a polysaccharide, and Eudragit® S100, an enteric polymer were selected to prepare microparticles for oral delivery of risedronate, an antiresorptive drug associated with GI tract injuries. Blend microparticles were prepared by spray-drying technique at 3 Pullulan and Eudragit® S100 ratios (MP2:1, MP1:1 and MP1:2) and were characterized in terms of yield, particle size, encapsulation efficiency, morphology, moisture content, flowability and in vitro drug release profiles. Microparticles presented yields between 31 and 42%, encapsulation efficiencies close to 100%, moisture contents lower than 11%, particle size ranging from 2.9 to 4.8 µm and narrow distribution. In the gastric medium, MP1:2 showed the best gastroresistance profile. In the intestinal fluid, all samples were able to prolong drug release. MP1:2 was compressed into tablets with or without polyvinylpyrrolidone. Both tableted microparticles could be obtained with acceptable average weights, drug content close to 100%, sufficient hardness and low friability. In vitro studies showed that tablets maintained the gastroresistance observed for microparticles and were also able to prolong risedronate release. In conclusion, Pullulan/Eudragit® S100 microparticles are promising alternatives for the oral delivery of risedronate in the future.

Haloperidol-loaded polysorbate-coated polymeric nanocapsules decrease its adverse motor side effects and oxidative stress markers in rats.

Haloperidol is the most widely used antipsychotic drug in the treatment of psychiatric disorders. Despite its satisfactory therapeutic effect, its chronic use is related to severe motor side effects. Here, we investigate the incidence of motor side effects of haloperidol-loaded nanocapsules when compared to free haloperidol and the relation with oxidative stress (OS) development. Both vehicle (B-NcFO) and haloperidol loaded polysorbate-coated nanocapsules suspension (H-NcFO) prepared with fish oil as core showed uniform and rounded particles, nanometric size, negative zeta potential, low polydispersity indices and high encapsulation efficiency. Wistar rats received a single dose of free haloperidol (FH), B-NcFO or H-NcFO (0.2 mg/kg ip) and were submitted to acute motor side effects evaluation 1 h after the injection. Lower catalepsy time and oral dyskinesia were observed in H-NcFO-treated group than in FH group; however, both formulations decreased animals' locomotor activity. In a experiment performed subchronically, rats injected daily with H-NcFO (0.2 mg/kg-ip) for 28 days showed decreased oral dyskinesia frequency and catalepsy time and no impairment on locomotor activity as compared to FH group (0.2 mg/kg-ip). FH group showed higher OS, as observed by increased lipid peroxidation and reduced glutathione levels and catalase activity in extrapyramidal region. Our findings showed that nanocapsules may be an efficient form to prevent or minimize haloperidol motor side effects, which are related to OS development, ameliorating psychiatric patients' quality of life.