Acostachurchill4058

The predictive tool, in the form of a user-friendly graphical user interface, was created based on the simplified model. The tool was adopted for in-house, bench-scale formulation development and scale-up because of its ease-of-use, good predicting capability, and very low material demand.Oral delivery of exenatide (EXE), a high-efficiency therapeutic peptide, is urgently needed for long-term treatment of diabetes. In this study, a polylactide-co-glycoside (PLGA) nanoparticles (NPs) in yeast cell wall particle (YCWP) system was built to improve the intestinal absorption of EXE by efficient protection of EXE against gastrointestinal degradation and intestinal phagocytic cell targeted delivery. The EXE-loaded PLGA NPs were prepared by a double emulsion solvent diffusion method and exhibited a uniformly spherical appearance, a nano size (92.4 ± 4.6 nm) and a positive surface charge (+32.3 ± 3.8 mV). And then, the NPs were successfully loaded into the YCWPs by a solvent hydration - lyophilization cycle method to obtain the EXE-PLGA NPs @YCWPs, which was verified by scanning electron microscope and confocal laser scanning microscopy. An obvious sustained drug release and a reduced burst release were achieved by this nano-in-micro carrier. Moreover, the gastrointestinal stability of EXE in PLGA NPs @YCWPs was significantly higher than that in PLGA NPs in the simulated gastrointestinal environment, which were useful in enhancing the intestinal absorption of EXE. In biodistribution study, the EXE-PLGA NPs @YCWPs could quickly reached the root of the villi, and even partly entered the inner of the villi, especially in ileum and Peyer's patches. In vitro cell evaluation demonstrated an efficient β-glucan receptor mediated endocytosis and transport of EXE-PLGA NPs @YCWPs by the macrophage RAW 264.7 cells, suggesting a potential intestinal macrophage targeted absorptive pathway. The in vivo pharmacokinetic study showed a preferred hypoglycemic effect and an increased pharmacological availability (13.7 ± 4.1%) after oral administration of the EXE-PLGA NPs @YCWPs. It is believed that the PLGA nanoparticles in YCWP system could become an efficient strategy to orally deliver therapeutic peptide drugs.We have developed a novel class of specifically engineered, dimerized cyclodextrin nanostructures for the encapsulation of toxic biomolecules such as 7-ketocholesterol (7KC). 7KC accumulates over time and causes dysfunction in many cell types, linking it to several age-related diseases including atherosclerosis and age-related macular degeneration (AMD). Presently, treatments for these diseases are invasive, expensive, and show limited benefits. Cyclodextrins (CDs) are cyclic glucose oligomers utilized to capture small, hydrophobic molecules. Here, a combination of in silico, in vitro, and ex vivo methods is used to implement a synergistic rational drug design strategy for developing CDs to remove atherogenic 7KC from cells and tissues. Mechanisms by which CDs encapsulate sterols are discussed, and we conclude that covalently linked head-to-head dimers of βCDs have substantially improved affinity for 7KC compared to monomers. We find that inclusion complexes can be stabilized or destabilized in ways that allow the design of CD dimers with increased 7KC selectivity while maintaining an excellent safety profile. These CD dimers are being developed as therapeutics to treat atherosclerosis and other debilitating diseases of aging.Inositol hexanicotinate (IHN) self-micelle solid dispersion (SD) with glycyrrhizic acid (GA) and arabic gum (AG) was prepared by mechanical ball milling process to improve the solubility, stability of amorphous state, and bioavailability of IHN, which enhanced the treatment of IHN on hyperlipidemia and nonalcoholic fatty liver disease (NAFLD). The physicochemical properties of IHN/GA/AG SDs in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscopy. The characteristics of the sample solutions were analyzed by reverse-phase HPLC, particle characterization, critical micelle concentration, and transmission electron microscopy. Further pharmacokinetic study of this SD formulation in rats showed a significant 3.3-fold increase in bioavailability compared to pure IHN. Moreover, biomarkers in serum and liver of NAFLD mice were significantly ameliorated after oral administration of IHN/GA/AG SDs for 15 days. find more Altogether, these results establish the mechanochemically prepared IHN/GA/AG SDs as an efficacious formulation for the treatment of hyperlipidemia and NAFLD.Biomimetic adhesive surfaces have a number of potential applications in the pharmaceutical and biomedical fields. Fabrication techniques must be adapted to biocompatible and biodegradable materials required for controlled drug release applications. In this study biomimetic adhesive poly(lactic-co-glycolic acid) (PLGA) films loaded with different concentrations of clotrimazole (CTZ) were prepared without combining other adhesive excipients as a controlled release system for potential local oral drug delivery. The films were fully characterized from morphological point of view, and CTZ-loaded biomimetic films exhibited adequate surface pH values, high drug encapsulation efficiency, and loading content. The adhesion strength of the obtained films was significantly higher compared to a flat film reference under different contact conditions. Thermal analysis indicated a decrease of drug crystallinity upon incorporation into PLGA films. The in vitro release of CTZ from PLGA biomimetic films was tested in simulated saliva, and it exhibited an initial burst release, accompanied by a sustained release phase over 10 days. Finally, the mucoadhesive properties of the obtained films was studied using agar/mucin plate as a representative mucosal substrate, and the results demonstrated superior mucoadhesion potential of CTZ-loaded biomimetic film in comparison to its flat counterpart. Having demonstrated the ability to load CTZ into PLGA biomimetic films with enhanced adhesion capacity, the potential use in local oral drug delivery applications warrants further in vitro and in vivo investigations.