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Purpose: Risperidone is an important antipsychotic agent used for treatment of both acute and chronic schizophrenia. The drug has been effective in resolving the disease's signs while keeping extrapyramidal side effects as low as possible. To achieve a sustained and gradual release of risperidone from PLGA microspheres, we utilized an emulsifying agent; PLGA-PEG-PLGA triblock (M-triblock), instead of PVA (M-PVA), applying ring-opening polymerization of the triblock via supercritical carbon dioxide (scCO2). Methods: PVA and PLGA-PEG-PLGA (as emulsifiers) were successfully employed to prepare risperidone-loaded PLGA microspheres. The scCO2 and microwave irradiation methods were used to construct PLGA-PEG-PLGA copolymers. The microspheres were subjected to various analyses to determine the particles' sizes, morphological characteristics, and structure (via XRD) and in vitro drug release kinetics. Drug loading capacity and encapsulation percentage were also determined. Results: The results showed a mean diameter of 43.34 ± 2.30 µm for M-PVA, and that of the M-triblock was 57.49 ± 1.21 µm. Risperidone encapsulation percentages were 72.8 ± 2.09 for M-PVAs and 73.4 ± 2.41 for the M-triblock. Particle size, risperidone distribution, and drug loading and encapsulation percentages were similar between M-PVAs and the M-triblock. In scanning electron microscopy (SEM), the morphology of the triblock emulsifier was more uniform than PVAs. Conclusions: The triblock emulsifier showed slower initial drug release than PVAs due to the precipitation of the triblock hydrogel around PLGA microspheres. Overall, the triblock used here can be a good alternative to PVA. [ABSTRACT FROM AUTHOR]

The crucial challenge in tuberculosis (TB) as a chronic infectious disease is to present a novel vaccine candidate that improves current vaccination and provides efficient protection in individuals. The present study aimed to evaluate the immune efficacy of multi-subunit vaccines containing chitosan (CHT)- or trimethyl chitosan (TMC)-coated PLGA nanospheres to stimulate cell-mediated and mucosal responses against Mycobacterium Tuberculosis (Mtb) in an animal model. The surface-modified PLGA nanoparticles (NPs) containing tri-fusion protein from three Mtb antigens were produced by the double emulsion technique. The subcutaneously or nasally administered PLGA vaccines in the absence or presence of BCG were assessed to compare the levels of mucosal IgA, IgG1, and IgG2a production as well as secretion of IFN-γ, IL-17, IL-4, and TGF-β cytokines. According to the release profile, the tri-fusion encapsulated in modified PLGA NPs demonstrated a biphasic release profile including initial burst release on the first day and sustained release within 18 days. All designed PLGA vaccines induced a shift of Th1/Th2 balance toward Th1-dominant response. Although immunized mice through subcutaneous injection elicited higher cell-mediated responses relative to the nasal vaccination, the intranasally administered groups stimulated robust mucosal IgA immunity. The modified PLGA NPs using TMC cationic polymer were more efficient to elevate Th1 and mucosal responses in comparison with the CHT-coated PLGA nanospheres. Our findings highlighted that the tri-fusion loaded in TMC-PLGA NPs may represent an efficient prophylactic vaccine and can be considered as a novel candidate against TB. [ABSTRACT FROM AUTHOR]

Background and the purpose of the study: A common approach in cancer chemotherapy is development of drugs that interrupt the mitosis phase of cell division. Dimethylenastron is a known kinesin inhibitor. In this study, six novel dimethylenastron analogues (4a-f), in which 3-hydroxyphenyl substituent has been replaced with substituted benzylimidazolyl, were synthesized through Biginelli reaction. Methods: Six novel Biginelli compounds (4a-f) were synthesized through one step Biginelli reaction of imidazole aldehydes (3a-c), dimedone and urea or thioura. In vitro cytotoxicities of prepared compounds were investigated using MTT assay. Furthermore the ELIPA kit was implemented to study inhibitory effects of synthesized compounds on ATPase activity of kinesin by measuring of organic phosphate. Results: Our results indicated that analogue 4c is the most toxic and analogues 4f, 4b and dimethylenasteron were less cytotoxic in compare with other analogues. On the other hand, analogue 4a, 4b, 4c and 4e showed stronger Kinesin inhibition as compared with analogue 4f and dimethylenasteron. None of synthesized compounds were as potent kinesin inhibitor as Taxol. Docking analysis revealed that hydrogen bond formation and hydrophobic interactions were the key factors affecting inhibitory effects of these compounds. Conclusion: Newly synthesized compounds were found to have moderate to good cytotoxicity against HeLa cancer cell. Our results may be helpful in further design of dihydropyrimidine as potential anticancer agents. [ABSTRACT FROM AUTHOR]