ABSTRACT
Aripiprazole (ARI), a second-generation atypical antipsychotic drug approved for schizophrenia treatment, shows good efficacy against depression. However, the poorly aqueous solubility of ARI leads to low bioavailability and increased dose-related side effects, seriously limiting its application in pharmaceutics. Herein, we demonstrated the fabrication of ARI and poly (methyl vinyl ether-co-maleic anhydride) (PVMMA) composite nanoparticles (PA NPs) using the supercritical antisolvent (SAS) process for enhancing its water-solubility and curative anti-depressant effects. Initially, the optimal experimental conditions (ARI/PVMMA mass ratio of 1:6, pressure of 10 MPa, and solution flow rate of 0.75 ml min-1) were determined by a 23 factorial experimental design, resulting in the PA NPs with an excellent particle morphology. In vitro cell experiments showed that PA NPs significantly inhibited the inflammatory response caused by the microglia activation induced by lipopolysaccharide (LPS). Similarly, mice behavioral tests demonstrated that PA NPs significantly improved LPS-induced depression-like behavior. Importantly, compared with free ARI, the LPS-induced activation of microglia in the mouse brain and the expression of inflammatory factors in serum were significantly reduced after treatment with PA NPs. Together, the innovative PA NPs designed by SAS process might provide a candidate for developing new ARI-based nano-formulations.
ABSTRACT
Due to its hydrophobicity, fisetin (FIS) often suffers from several limitations in terms of its applicability during the fabrication of pharmaceutical formulations. To overcome this intrinsic limitation of hydrophobicity, we demonstrate here the generation of poly (vinyl pyrrolidone) (PVP)-encapsulated FIS nanoparticles (FIS-PVP NPs) utilizing a supercritical antisolvent (SAS) method to enhance its aqueous solubility and substantial therapeutic effects. In this context, the effects of various processing and formulation parameters, including the solvent/antisolvent ratio, drug/polymer (FIS/PVP) mass ratio, and solution flow rate, on the eventual particle size as well as on distribution were investigated using a 23 factorial experimental design. Notably, the FIS/PVP mass ratio significantly affected the morphological attributes of the resultant particles. Initially, the designed constructs were characterized systematically using various techniques (e.g., chemical functionalities were examined with Fourier-transform infrared (FTIR) spectroscopy, and physical states were examined with X-ray diffraction analysis (XRD) and differential scanning calorimetry (DSC) techniques). In addition, drug release as well as cytotoxicity evaluations in vitro indicated that the nanosized polymer-coated particles showed augmented performance efficiency compared to the free drug, which was attributable to the improvement in the dissolution rate of the FIS-PVP NPs due to their small size, facilitating a higher surface area over the raw form of FIS. Our findings show that the designed SAS process-assisted nanoconstructs with augmented bioavailability, have great potential for applications in pharmaceutics.
ABSTRACT
AIM: To prepare and identify monoclonal antibodies(mAbs) against human secretory leukocyte protease inhibitor (hSLPI). METHODS: BALB/c mice were immunized with hSLPI, and hybridoma cell lines were obtained by fusing mouse spleen cells with myeloma NS-1 cells. The specificity of mAbs were characterized by ELISA, Western blot, immunohistochemical staining, flow cytometry(FCM) and confocal laser scanning microscopy(CLSM). RESULTS: Four hybridoma cells which secreted the mAbs to hSLPI were obtained. 4 mAbs were IgM. Western blot analysis showed that the mAbs could recognize a target molecule with relative molecular mass of 12 000. Immunohistochemical staining revealed that the reactivities of 4 mAbs to the epithelial cells in lung and colon tissues, mast cell-like cells in lung, colon, tonsil and prepuce tissues were positive. The result of FCM showed that the 4 mAbs recognized SLPI expressed in A549 cells. CLSM examination confirmed that the fluorescent markers were mainly localized in the cytoplasm of A549 cells. CONCLUSION: The mAbs against hSLPI are prepared successfully, which provides valuable tool for studies on allergic and inflammatory diseases.
