Biopharmaceutics studies applied to goyazensolide: a drug candidate from Lychnophora species.

OBJECTIVES: To predict the substance's behaviour in vivo and determine the viability of the bioactive substance to become a drug, this work aimed to evaluate the biopharmaceutics characteristics of goyazensolide. METHODS: Differential scanning calorimetry (DSC) and thermogravimetry (TG) were applied for the characterization of goyazensolide. The biopharmaceutics characteristics were evaluated using in-silico and in-vitro (shake-flask and Parallel Artificial Membrane Permeability Assay) methods. KEY FINDINGS: DSC curve showed a single endothermic peak. According to the TG curve, goyazensolide has thermal stability close to 221.0°C and 210.0°C, under a nitrogen and oxygen atmosphere, respectively. In-silico data indicated that goyazensolide has high solubility and low permeability. The high solubility was confirmed by equilibrium solubility studies determined by the shake-flask method. The dose/solubility ratio values were 175.16 ml (pH 1.2), 194.99 ml (pH 4.5) and 222.07 ml (pH 6.8). The effective permeability of 0.03 × 10-6 cm/s was obtained for goyazensolide. This value is lower than furosemide (1.03 × 10-6 cm/s), confirming the low permeability of goyazensolide. CONCLUSIONS: Biopharmaceutics characteristics of goyazensolide are similar to drugs available on the market and attest to the feasibility of starting the process of developing a formulation containing this substance.

Encapsulation of safflower oil in nanostructured lipid carriers for food application.

Safflower oil (SO) is mainly rich in linoleic acid (ω-6), oleic acid (ω-9), and other bioactives with potential antioxidant, antidiabetic, thermogenic, anti-inflammatory, cardioprotective and anticancer activities. The reduced aqueous solubility and high susceptibility to oxidative degradation are undesirable for food applications and can be overcome by incorporation in lipid nanoparticles. Thus, the main goal was to develop and characterize SO-loaded nanostructured lipid carriers (NLC-SO) and to evaluate their potential for protection of the antioxidant activity of the bioactive. NLC-SO showed average size of 222 ± 2.0 nm, zeta potential of  43 ± 3.5 mV and the encapsulation efficiency was 49.0 ± 2.8%, combined with high thermal compatibility (up to 228 °C) and physical stability for up to 60 days in aqueous dispersion. Besides, the NLC-SO showed threefold reduction in the DPPH radical scavenge activity after encapsulation, indicating protection of the antioxidant components of the SO and preservation of the bioactives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-021-05078-5.

Synthesis and characterization of a molecularly imprinted polymer (MIP) for solid-phase extraction of the antidiabetic gliclazide from human plasma.

Gliclazide is a sulfonylurea frequently prescribed for the management of type 2 diabetes mellitus in elderly patients and for patients with chronic renal or hepatic diseases. Even though it is considered a safer alternative, the drug can provoke side effects in some patients, especially hypoglycemia, due to the high interindividual variability. Therefore, the quantification of gliclazide in biological samples is usually recommended in order to assure efficacy and safety of the pharmacotherapy. However, due to the complexity of biological matrices, therapeutic monitoring can be very challenging, especially in the sample preparation step. For that reason, the synthesis and characterization of a novel and selective molecularly imprinted polymer (MIP) was proposed to be employed as sorbent for the extraction of gliclazide from human plasma samples by a molecularly imprinted solid-phase extraction (MISPE) procedure. Synthesis conditions were optimized (monomer, crosslinker and porogen) and the polymer was characterized for its morphological, physicochemical and stability properties. The influence of drug concentration, solvent composition and pH on the coefficient of distribution (Kd) and imprinting factor (IF) were studied, as well as repeatability between batches and selectivity. A bioanalytical method was developed applying the developed MIP as sorbent in solid phase extraction and liquid chromatography using a Poroshell 120 C18 (100 × 4.6 mm, 4 µm) column, acetonitrile and 10 mM potassium phosphate buffer pH 3.0 (50:50) at a flow-rate of 1.2 mL/min as mobile phase, temperature of 30 °C, injection volume of 40 µL and detection at 230 nm. The best reaction yield, extraction capacity, and selectivity was obtained using 2-hydroxyethyl methacrylate (2-HEMA), ethyleneglycol dimethacrylate (EGDMA) and acetonitrile. The optimized MIP showed coefficient of distribution (Kd) of 59.85 µg/g, imprinting factor (IF) of 1.60, and selectivity for gliclazide and other sulfonylureas compared to possible concurrent drugs. The developed method by MISPE-HPLC-UV showed to be appropriate to determine gliclazide in human plasma samples.

Amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid for the treatment of vulvovaginal candidiasis.

The treatment of vulvovaginal candidiasis (VVC) is based on oral and vaginal formulations which show limited effectiveness. In this study, amphotericin B-loaded Eudragit RL100 nanoparticles coated with hyaluronic acid (AMP EUD nanoparticles/HA) were developed to overcome the drawbacks of the conventional formulations. AMP EUD nanoparticles/HA were synthesized by nanoprecipitation, formulated by statistical experimental design, and characterized. AMP release from EUD nanoparticles/HA and its antifungal activity in a murine model of VVC were evaluated. Nanoparticles showed 147.6 ±â€¯16.7 nm of diameter, 0.301 ±â€¯0.09 of polydispersity index, - 29.9 ±â€¯3.76 mV of zeta potential, and 87.27 % of encapsulation efficiency. They released about 81 % of AMP in 96 h; and provided the elimination of 100 % of the vaginal fungal burden in 24 h. It was suggested that the AMP EUD nanoparticles/HA penetrated into the vaginal epithelium via CD44 receptors. These AMP EUD nanoparticles/HA represent a non-conventional vaginal formulation to improve the treatment of VVC.