Floating drug delivery system (FDDS) are of particular interest for drugs that are locally active and have narrow absorption window in stomach or upper small intestine, unstable in the intestinal or colonic environment, and exhibit low solubility at high pH values. The Micro sponge Delivery System (MDS) is a patented polymeric system consisting of porous microspheres. These are tiny sponge like spherical particles that consist of a myriad of interconnecting voids within a non-collapsible structure with a large porous surface through which active ingredient are released in a controlled manner. Famotidine floating microsponges are prepared to improve site specific absorption of drug for peptic ulcer treatment. Modified quasi emulsion solvent diffusion method was used to formulate microsponges. Different concentrations of EudragitS100 and Polyvinyl alcohol were used and the prepared microsponges were evaluated for % entrapment efficiency, % buoyancy and % cumulative drug release. It was found that the % entrapment efficiency was 88.3%, % buoyancy was 76.4% and % cumulative drug release was 86.9% for F6 formulation. This study presents a new approach based on floating ability of microsponges for treatment of ulcer.
Extracellular vesicles (EVs) are highly interesting for the design of next-generation therapeutics. However, their preparation methods face challenges in standardization, yield, and reproducibility. Here, we describe a highly efficient and reproducible EV preparation method for monodisperse nano plasma membrane vesicles (nPMVs), which yields 10 to 100 times more particles per cell and hour than conventional EV preparation methods. nPMVs are produced by homogenizing giant plasma membrane vesicles following cell membrane blebbing and apoptotic body secretion induced by chemical stressors. nPMVs showed no significant differences compared to native EVs from the same cell line in cryo-TEM analysis, in vitro cellular interactions, and in vivo biodistribution studies in zebrafish larvae. Proteomics and lipidomics, on the other hand, suggested substantial differences consistent with the divergent origin of these two EV types and indicated that nPMVs primarily derive from apoptotic extracellular vesicles. nPMVs may provide an attractive source for developing EV-based pharmaceutical therapeutics.
Introduction: Blood infections from multi-drug-resistant Salmonella pose a major health burden. This is especially true because Salmonella can survive and replicate intracellularly, and the development of new treatment strategies is dependent on expensive and time-consuming in vivo trials. The aim of this study was to develop a Salmonella-infection model that makes it possible to directly observe Salmonella infections of macrophages in vivo and to use this model to test the effect of antimicrobials against intra-and extracellular Salmonella in order to close the gap between in vitro and rodent-infection models. Methods: We established suitable Salmonellainfection conditions using genetically engineered zebrafish and Salmonella-expressing fluorescent proteins (green fluorescent protein (GFP) and/or mCherry). Results: We detected Salmonella inside and outside zebrafish larvae macrophages. Administration of the cellimpermeable antibiotic tobramycin removed Salmonella residing outside macrophages but did not affect Salmonella in macrophages, whereas ceftriaxone successfully cleared both types of Salmonella. Salmonella inside and outside macrophages experienced substantial DNA damage after administration of fluoroquinolones consistent with the excellent cell penetration of these antibiotics. Conclusions:The zebrafish-larvae model enables testing of antimicrobials for efficacy against extra-and intracellular Salmonella in a complex in vivo environment. This model thus might serve for antimicrobial lead optimization prior to using rodent models.
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