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Bacterial infections are a significant cause of mortality and morbidity worldwide, despite decades of use of numerous existing antibiotics and constant efforts by researchers to discover new antibiotics. The emergence of infections associated with antibiotic-resistant bacterial strains, has amplified the pressure to develop additional bactericidal therapies or new unorthodox approaches that can deal with antimicrobial resistance. Nanomaterial-based strategies, particularly those that do not rely on conventional small-molecule antibiotics, offer promise in part due to their ability to dodge existing mechanisms used by drug-resistant bacteria.
View Article and Find Full Text PDFWhen administered orally, the bioavailability of drugs is strongly influenced by their aqueous solubility and permeability. Although solubility-enabling excipients can improve the aqueous solubility of lipophilic drugs, their simultaneous effect on the apparent permeability can be often overlooked. Recently, we demonstrated that the aqueous dissolution of poorly aqueous soluble benznidazole (BNZ) was improved by γ-CD complexation, but the potential impact of γ-CD complexation on the permeability of BNZ remained unexplored.
View Article and Find Full Text PDFVancomycin (Van) is a key antibiotic of choice for the treatment of systemic methicillin resistant (MRSA) infections. However, due to its poor membrane permeability, it is administered parenterally, adding to the cost and effort of treatment. The poor oral bioavailability of Van is mainly due to its physico-chemical properties that limit its paracellular and transcellular transport across gastrointestinal (GI) epithelium.
View Article and Find Full Text PDFBenznidazole (BZ) and nifurtimox are first-line drugs for the treatment of Chagas disease, with BZ preferred due to its moderate side effects compared to nifurtimox. However, BZ has low aqueous solubility and a low dissolution rate which potentially limit its oral bioavailability. We now report for the first time efforts to improve the aqueous dissolution of BZ via processing and γ-cyclodextrin (γ-CD) complexation using supercritical carbon dioxide (scCO).
View Article and Find Full Text PDFAntibiotic resistance has become a global crisis, driving the exploration for novel antibiotics and novel treatment approaches. Among these research efforts two classes of antibiotics, bicyclic nitroimidazoles and antimicrobial peptides, have recently shown promise as novel antimicrobial agents with the possibility to treat multi-drug resistant infections. However, they suffer from the issue of poor oral bioavailability due to disparate factors: low solubility in the case of nitroimidazoles (BCS class II drugs), and low permeability in the case of peptides (BCS class III drugs).
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