Intracellular bacterial pathogens are hard to treat because of the inability of conventional antimicrobial agents belonging to widely used classes, like aminoglycosides and β-lactams, fluoroquinolones, or macrolides to penetrate, accumulate, or be retained in the mammalian cells. The increasing problem of antibiotic resistance complicates more the treatment of the diseases caused by these agents. In many cases, the increase in therapeutic doses and treatment duration is accompanied by the occurrence of severe side effects. Taking into account the huge financial investment associated with bringing a new antibiotic to the market and the limited lifetime of antibiotics, the design of drug delivery systems to enable the targeting of antibiotics inside the cells, to improve their activity in different intracellular niches at different pH and oxygen concentrations, and to achieve a reduced dosage and frequency of administration could represent a prudent choice. An ideal drug delivery system should possess several properties, such as antimicrobial activity, biodegradability, and biocompatibility, making it suitable for use in biomedical and pharmaceutical formulations. This approach will allow reviving old antibiotics rendered useless by resistance or toxicity, rescuing the last line therapy antibiotics by increasing the therapeutic index, widening the antimicrobial spectrum of antibiotics scaffolds that failed due to membrane permeability problems, and thus reducing the gap between increasingly drug-resistant pathogens and the development of new antibiotics. Different improved drug carriers have been developed for treating intracellular pathogens, including antibiotics loaded into liposomes, microspheres, polymeric carriers, and nanoplexes. The purpose of this chapter is to present the limitations of each class of antibiotics in targeting intracellular pathogens and the main research directions for the development of drug delivery systems for the intracellular release of antibiotics.
Part of the book: Smart Drug Delivery System
The most recent World Health Organization report revealed that the number of adults suffering from diabetes has almost quadrupled since 1980 to 422 million, thus drawing attention to the urgent need to step up prevention and treatment of this disease. This chronic ailment is often associated with serious complications such as increased risk of heart disease, stroke and kidney failure. In 2012 alone, diabetes lead to 1.5 million deaths. This dramatic rise is mainly due to the increased prevalence of type 2 diabetes and factors driving it include overweight and obesity. Novel studies in this area have advanced our understanding regarding the complex relationship between diet, gut microbiota and diabetes. Despite no clear microbiota signature is associated with diabetes, patients harbour a reduction of butyrate-producing species (Faecalibacterium prausnitzii, Roseburia intestinalis) as well as an increase in opportunistic pathogens. Furthermore, the functions of the gut microbiome (i.e., vitamin metabolism, transport of sugars, carbohydrate metabolism, short chain fatty acid (SCFA) synthesis, etc.) are also different in patients with type 2 diabetes, a fact that may significantly alter the course of disease. Diet is one of the most decisive factors that have an impact on the gut microbiome. Nutritional interventions using prebiotics (i.e., inulin-type fructans), polyphenols and arabinoxylans have been employed for the treatment of diabetes. Besides the shifts produced by these dietary components in the microbiome composition, it is worth mentioning their impact on host physiology through modulation of gut peptide production and glucose metabolism. The information presented within this chapter summarizes the most recent advances in the study of the microbiome-diet-diabetes interplay and analyses how these novel findings can be used in order to establish new therapeutic approaches for those with diabetes.
Part of the book: Pathophysiology