Adapalene-loaded poly(ε-caprolactone) microparticles: Physicochemical characterization and in vitro penetration by photoacoustic spectroscopy.

Adapalene (ADAP) is an important drug widely used in the topical treatment of acne. It is a third-generation retinoid and provides keratolytic, anti-inflammatory, and antiseborrhoic action. However, some topical adverse effects such as erythema, dryness, and scaling have been reported with its commercial formula. In this sense, the microencapsulation of this drug using polyesters can circumvent its topical side effects and can lead to the enhancement of drug delivery into sebaceous glands. The goal of this work was to obtain ADAP-loaded poly(ε-caprolactone) (PCL) microparticles prepared by a simple emulsion/solvent evaporation method. Formulations containing 10 and 20% of ADAP were successfully obtained and characterized by morphological, spectroscopic, and thermal studies. Microparticles presented encapsulation efficiency of ADAP above 98% and showed a smooth surface and spherical shape. Fourier transform infrared spectroscopy (FTIR) results presented no drug-polymer chemical bond, and a differential scanning calorimetry (DSC) technique showed a partial amorphization of the drug. ADAP permeation in the Strat-M membrane for transdermal diffusion testing was evaluated by photoacoustic spectroscopy (PAS) in the spectral region between 225 and 400 nm after 15 min and 3 h from the application of ADAP-loaded PCL formulations. PAS was successfully used for investigating the penetration of polymeric microparticles. In addition, microencapsulation decreased the in vitro transmembrane diffusion of ADAP.

A Stability-Indicating HPLC-DAD Method for Determination of Ferulic Acid into Microparticles: Development, Validation, Forced Degradation, and Encapsulation Efficiency.

A simple stability-indicating HPLC-DAD method was validated for the determination of ferulic acid (FA) in polymeric microparticles. Chromatographic conditions consisted of a RP C18 column (250 mm × 4.60 mm, 5 µm, 110 Å) using a mixture of methanol and water pH 3.0 (48 : 52 v/v) as mobile phase at a flow rate of 1.0 mL/min with UV detection at 320 nm. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of quantification, limit of detection, accuracy, precision, and robustness provided suitable results regarding all parameters investigated. The calibration curve was linear in the concentration range of 10.0-70.0 µg/mL with a correlation coefficient >0.999. Precision (intraday and interday) was demonstrated by a relative standard deviation lower than 2.0%. Accuracy was assessed by the recovery test of FA from polymeric microparticles (99.02% to 100.73%). Specificity showed no interference from the components of polymeric microparticles or from the degradation products derived from acidic, basic, and photolytic conditions. In conclusion, the method is suitable to be applied to assay FA as bulk drug and into polymeric microparticles and can be used for studying its stability and degradation kinetics.

PCL/PHBV microparticles as innovative carriers for oral controlled release of manidipine dihydrochloride.

Microparticles of poly(ε-caprolactone) (PCL) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) containing manidipine dihydrochloride (MAN) were successfully prepared by the simple emulsion/solvent evaporation method. All formulations showed loading efficiency rates greater than 80% and average particle size less than 8 µm. Formulations had spherical shape with smooth and porous surface for PCL and PHBV, respectively. According to Fourier-transform infrared spectroscopy, initial components were not chemically modified during microencapsulation. X-ray diffraction patterns and differential scanning calorimetry demonstrated that this process led to drug amorphization. In vitro dissolution studies showed that all microparticles prolonged MAN release, mainly which one obtained using PCL that contained 5% of drug loaded (PCL-M5). Animal studies demonstrated that formulation PCL-M5 was able to keep the variation of mean arterial pressure after phenylephrine administration up to 24 hours. These data confirmed the sustained antihypertensive effect of the investigated microparticles. Results provided an experimental basis for using formulation PCL-M5 as a feasible carrier for oral controlled release of MAN intended for treating high blood pressure.

In Vitro Cytotoxic Potential of Essential Oils of Eucalyptus benthamii and Its Related Terpenes on Tumor Cell Lines.

Eucalyptus L. is traditionally used for many medicinal purposes. In particular, some Eucalyptus species have currently shown cytotoxic properties. Local Brazilian communities have used leaves of E. benthamii as a herbal remedy for various diseases, including cancer. Considering the lack of available data for supporting this cytotoxic effect, the goal of this paper was to study the in vitro cytotoxic potential of the essential oils from young and adult leaves of E. benthamii and some related terpenes (α-pinene, terpinen-4-ol, and γ-terpinene) on Jurkat, J774A.1 and HeLa cells lines. Regarding the cytotoxic activity based on MTT assay, the essential oils showed improved results than α-pinene and γ-terpinene, particularly for Jurkat and HeLa cell lines. Terpinen-4-ol revealed a cytotoxic effect against Jurkat cells similar to that observed for volatile oils. The results of LDH activity indicated that cytotoxic activity of samples against Jurkat cells probably involved cell death by apoptosis. The decrease of cell DNA content was demonstrated due to inhibition of Jurkat cells proliferation by samples as a result of cytotoxicity. In general, the essential oils from young and adult leaves of E. benthamii presented cytotoxicity against the investigated tumor cell lines which confirms their antitumor potential.

Chemical composition, toxicity and mosquito repellency of Ocimum selloi oil.

Ocimum spp. (Lamiaceae) and their essential oils have been traditionally used to kill or repel insects, and also to flavor foods and oral products, in fragrances, in folk medicine and as condiments. In Brazil, Ocimum selloi has been used to treat stomachaches and as an anti-inflammatory remedy. This study was performed to provide data on the chemical composition, acute toxicity, mutagenicity, skin irritant potential and mosquito repellency of Ocimum selloi oil. GC/MS analysis of Ocimum selloi oil revealed that its major constituents were methyl-chavicol or estragole (55.3%), trans-anethole (34.2%), cis-anethole (3.9%) and caryophyllene (2.1%). Ocimum selloi oil given by gavage to adult Swiss Webster mice produced no adverse effects at doses as high as 1250 mg/kg body weight. Deaths and symptoms (e.g. hypoactivity, ataxia and lethargy) were observed at doses > or =1500 mg/kg body weight, being females apparently more susceptible than males. Genotoxicity of Ocimum selloi oil was evaluated in the Salmonella/microsome assay without and with S9 mixture. The oil, tested up to the toxicity limit (500-700 microg/plate), was not mutagenic to tester strains TA97a, TA98 and TA100. None of 30 volunteers of either sex exposed to undiluted Ocimum selloi oil (4-h patch test) showed a positive skin irritant reaction. A field test (six volunteers, each individual his/her own control) was carried out to evaluate mosquito (Anopheles braziliensis) repellency of Ocimum selloi oil diluted in ethanol (10% v/v). The median number of mosquito bites on volunteers' skin-recorded for 30 min after application of Ocimum selloi oil (2, range 0-3) was much lower than that noted after application of the solvent alone (19.5, 3-25) (Wilcoxon test, P<0.01). In conclusion, results showed that Ocimum selloi oil is an effective mosquito repellent that presents a low acute toxicity, poses no mutagenic risk and seems not to be irritating to human skin.