Preparation and optimization of resveratrol nanosuspensions by antisolvent precipitation using Box-Behnken design.

Resveratrol, a natural polyphenolic component, has inspired considerable interest for its extensive physiological activities. However, the poor solubility of resveratrol circumscribes its therapeutic applications. The purpose of this study was to optimize and prepare resveratrol nanosuspensions using the antisolvent precipitation method. The effects of crucial formulation and process variables (drug concentration, stabilizer, and surfactant contents) on particle size were investigated by utilizing a three-factor three-level Box-Behnken design (BBD) to perform this experiment. Different mathematical polynomial models were used to identify the impact of selected parameters and to evaluate their interrelationship for predictive formulation purposes. The optimal formulation consisted of drug 29.2 (mg/ml), polyvinylpyrrolidone (PVP) K17 0.38%, and F188 3.63%, respectively. The morphology of nanosuspensions was found to be near-spherical shaped by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis confirmed that the nanoparticles were in the amorphous state. Furthermore, in comparison to raw material, resveratrol nanosuspensions showed significantly enhanced saturation solubility and accelerated dissolution rate resulting from the decrease in particle size and the amorphous status of nanoparticles. Meanwhile, resveratrol nanosuspensions exhibited the similar antioxidant potency to that of raw resveratrol. The in vivo pharmacokinetic study revealed that the C max and AUC0→∞ values of nanosuspension were approximately 3.35- and 1.27-fold greater than those of reference preparation, respectively. Taken together, these results suggest that this study provides a beneficial approach to address the poor solubility issue of the resveratrol and affords a rational strategy to widen the application range of this interesting substance.

Differences in epithelial-mesenchymal-transition in paraquat-induced pulmonary fibrosis in BALB/C and BALB/C (nu/nu) nude mice.

Exposure to the toxic herbicide paraquat (PQ) can lead to the active absorption and enrichment of alveolar epithelial cells, resulting in pulmonary fibrosis and respiratory failure. At present, no effective clinical treatment is available. Notably, however, patients infected with human acquired immunodeficiency virus (HIV) (with T lymphocyte deficiency) do not show pulmonary fibrosis after PQ poisoning, suggesting that T lymphocytes may be involved in the occurrence and pathological development of lung fibers following PQ exposure, although relevant studies remain limited. Here, we found that the degree of pulmonary fibrosis induced by intragastric administration of PQ in congenital immunodeficiency BALB/C (nu/nu) nude (T lymphocyte loss) mice was lower than that in normal mice. However, pulmonary fibrosis was aggravated after transplantation of BALB/C (nu/nu) T lymphocytes into congenital immunodeficiency mice. This study is the first to report on the involvement of T lymphocytes in the occurrence and pathological development of lung fibers induced by PQ exposure. Thus, T cells may be an important cellular target for the clinical treatment of pulmonary fibrosis caused by PQ.

Fabrication of a composite system combining solid lipid nanoparticles and thermosensitive hydrogel for challenging ophthalmic drug delivery.

The purpose of this study was to explore a composite thermosensitive in situ gelling formulation using the distribution of solid lipid nanoparticles (SLNs) among poloxamer-based hydrogels as a potential carrier for novel ocular drug delivery. SLNs containing the model drug Resina Draconis were prepared using a melt-emulsion ultrasonication method. A central composite design (CCD) was adopted to screen the thermosensitive hydrogel (THG) formulation. After aqueous SLNs were dispersed into the THG matrices, the physicochemical properties of the SLNs were characterized before and after their incorporation into hydrogels. The in vitro corneal penetration experiment, ocular irritant test and transcorneal mechanism across the cornea have been previously described to predict the feasibility for the proposed ophthalmic application. Finally, the optimal THGs consisted of 27.8% (w/v) poloxamer 407 and 3.55% (w/v) poloxamer 188. The particle size of the SLNs remained within the colloidal range. In vitro corneal penetration studies revealed a nearly steady sustained drug release. The hen's egg test-chorioallantoic membrane (HET-CAM) test indicated that all of the tested polymer systems were non-irritant. Coumarin-6 labeled SLNs formulated into THGs displayed a more homogeneous fluorescence with a deeper penetration intensity into the cornea at various times. Taken together, these results suggest that the SLN-based THG system can be used as a potential vehicle for ocular application.