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.
Nephrotoxicity is an important drug safety aspect to be assessed during drug discovery and development. To study renal toxicity, in vitro cell-based assays are often used. Unfortunately, translating the results of such cell assays to vertebrates including human remains challenging. Therefore, we aim to evaluate whether zebrafish larvae (ZFL) could serve as a vertebrate screening model to detect gentamicin-induced changes of kidney glomeruli and proximal tubules. To validate the model, we compared the results of ZFL with those obtained from kidney biopsies of gentamicin-treated mice. We used transgenic zebrafish lines expressing enhanced green fluorescent proteins in the glomerulus to visualize glomerular damage. Synchrotron radiation-based computed tomography (SRμCT) is a label-free approach providing three-dimensional representations of renal structures with micrometre resolution. Clinically used gentamicin concentrations induce nephrotoxicity and affect glomerular and proximal tubular morphology. Findings were confirmed in mice and ZFL. There was a strong correlation between fluorescent signals in ZFL, SRμCT- derived descriptors of glomerular and proximal tubular morphology and the histological analysis of mouse kidney biopsies. A combination of SRμCT and confocal microscopy provides unprecedented insights into anatomical structures of the zebrafish kidney. Based on our findings, we suggest to use ZFL as a predictive vertebrate screening model to study drug-induced nephrotoxicity and to bridge the gap between cell culture-based test systems and experiments in mammals.
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