Effect of triacylglycerol composition around the antioxidant task involving oryzanol

Co-amorphous drug delivery systems are evolving as a credible alternative to amorphous solid dispersions technology. In Co-amorphous systems (CAMs), a drug is stabilized in amorphous form using small molecular weight compounds called as co-formers. A wide variety of small molecular weight co-formers have been leveraged in the preparation of CAMs. The stability and supersaturation potential of prepared co-amorphous phases largely depend on the type of co-former employed in the CAMs. However, the rationality behind the co-former selection in co-amorphous systems is poorly understood and scarcely compiled in the literature. There are various facets to the rational selection of co-former for CAMs. In this context, the present review compiles various factors affecting the co-former selection. The factors have been broadly classified under Thermodynamic, Kinetic and Pharmacokinetic-Pharmacologically relevant parameters. In particular, the importance of Glass transition, Miscibility, Liquid-Liquid phase separation (LLPS), Crystallization inhibition has been deliberated in detail.Pancreatic cancer, as one of the most aggressive and lethal malignancies in the world, is lack of effective treatment. Constructing immunotoxin molecules to target the mesothelin (MSLN) receptor is a potential therapeutic strategy for pancreatic cancer and other related malignant tumors, with some molecules being tested in clinical trials. However, currently, there are still some limitations in its applications, such as the difficulty of the preparation of drug molecules, the limited effectiveness of drugs, and the inadequacy of drug safety and immunogenicity. In this study, we constructed a novel type of anti-MSLN immunotoxin, A1-PE24X7, in which a single domain antibody (sdAb) molecule was used as the target ligand and an improved PE24X7 toxin with reduced off-target toxicity and immunogenicity was used as the effector. Unlike conventional immunotoxins, the designed A1-PE24X7 could be easily expressed in the E. coli system in the form of a soluble protein with a good yield (15--20 mg/L), avoiding the complelatively broad therapeutic window. These preclinical results indicate that this strategy has good potential for application to the treatment of pancreatic cancer and other tumors with high MSLN expression.Central nervous system tuberculosis (CNS-TB) is the most severe form of the disease especially due to the inability of therapeutics to cross the blood-brain barrier (BBB). Clofazimine (CFZ) stands out for presenting high in vitro activity against multi-drug resistant strains of Mycobacterium tuberculosis, however, CFZ physicochemical and pharmacokinetics properties limit drug penetration into the CNS and, consequently, its clinical use. The aim of this work was to develop polymeric nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) loaded with CFZ and functionalized with a transferrin receptor (TfR)-binding peptide, aiming brain drug delivery for CNS-TB treatment by the intravenous route. The poor water solubility and high lipophilicity of CFZ was overcome through its entrapment into PLGA-PEG NPs manufactured by both conventional and microfluidic techniques using the nanoprecipitation principle. In vitro studies in brain endothelial hCMEC/D3 cells demonstrated that CFZ incorporation into the NPs was advantageous to reduce drug cytotoxicity. PARP inhibitor The TfR-binding peptide-functionalized NPs showed superior cell interaction and higher CFZ permeability across hCMEC/D3 cell monolayers compared to the non-functionalized NP control, thus indicating the efficacy of the functionalization strategy on providing CFZ transport through the BBB in vitro. The functionalized NPs demonstrate suitability for CFZ biological administration, suggested with low plasma protein binding, off-target biodistribution and precise delivery of CFZ towards the brain parenchyma.In the pharmaceutical industry, linear die filling is widely employed in R&D, while rotary die filling is very common in commercial production. It is not clear if powder die filling behaviour in a linear die filling system is representative of the flow performance in a rotary tablet press. In this study, a linear die filling system and a rotary die filling system were used to examine flow behaviours of both poor-flowing and free-flowing powders. It was found that the performance of poor-flowing powder in the linear die filling system is slightly better than that in the rotary die filling system, while the performance of free-flowing powders in the linear die filling system is similar to that in the rotary die filling system. Hence, it is suitable to use the linear die filling system to estimate the flow behaviour during rotary die filling with free-flowing powders, but caution needs to be taken when poor-flowing powders are used.High-grade glioma is one of the most aggressive types of cancer with a low survival rate ranging from 12 to 15 months after the first diagnosis. Though being the most common strategy for glioma therapy, conventional chemotherapy suffers providing the therapeutic dosage of common therapeutics mostly because of limited permeability of blood-brain barrier (BBB), and blood-brain tumor barrier (BBTB) to anticancer agents. Among various nanoformulations, liposomes are considered as the most popular carriers aimed for glioma therapy. However, non-targeted liposomes which passively accumulate in most of the cancer tissues mainly through the enhanced permeation and retention effect (EPR), may not be applicable for glioma therapy due to BBB tight junctions. In the recent decade, the surface modification of liposomes with different active targeting ligands has shown promising results by getting different chemotherapeutics across the BBB and BBTB and leading them into the glioma cells. The present review discusses the major barriers for drug delivery systems to glioma, elaborates the existing mechanisms for liposomes to traverse across the BBB, and explores the main strategies for incorporation of targeting ligands onto the liposomes. It subsequently investigates the most recent and relevant studies of actively targeted liposomes modified with antibodies, aptamers, monosaccharides, polysaccharides, proteins, and peptides applied for effective glioma therapy, and highlights the common challenges facing this area. Finally, the actively targeted liposomes undergoing preclinical and clinical studies for delivery of different anticancer agents to glioma cells will be reviewed.