Strategies and progresses for enhancing targeted antibiotic delivery.

Antibiotic resistance is a global health issue and a potential risk for society. Antibiotics administered through conventional formulations are devoid of targeting effect and often spread to various undesired body sites, leading to sub-lethal concentrations at the site of action and thus resulting in emergence of resistance, as well as side effects. Moreover, we have a very slim antibiotic pipeline. Drug-delivery systems have been designed to control the rate, time, and site of drug release, and innovative approaches for antibiotic delivery provide a glint of hope for addressing these issues. This review elaborates different delivery strategies and approaches employed to overcome the limitations of conventional antibiotic therapy. These include antibiotic conjugates, prodrugs, and nanocarriers for local and targeted antibiotic release. In addition, a wide range of stimuli-responsive nanocarriers and biological carriers for targeted antibiotic delivery are discussed. The potential advantages and limitations of targeted antibiotic delivery strategies are described along with possible solutions to avoid these limitations. A number of antibiotics successfully delivered through these approaches with attained outcomes and potentials are reviewed.

A Comparative Insight on the Newly Emerging Rifamycins: Rifametane, Rifalazil, TNP-2092 and TNP-2198.

Rifamycins are considered a milestone for tuberculosis (TB) treatment because of their proficient sterilizing ability. Currently, available TB treatments are complicated and need a long duration, which ultimately leads to failure of patient compliance. Some new rifamycin derivatives, i.e., rifametane, TNP-2092 (rifamycin-quinolizinonehybrid), and TNP-2198 (rifamycin-nitromidazole hybrid) are under clinical trials, which are attempting to overcome the problems associated with TB treatment. The undertaken review is intended to compare the pharmacokinetics, pharmacodynamics and safety profiles of these rifamycins, including rifalazil, another derivative terminated in phase II trials, and already approved rifamycins. The emerging resistance of microbes is an imperative consideration associated with antibiotics. Resistance development potential of microbial strains against rifamycins and an overview of chemistry, as well as structure-activity relationship (SAR) of rifamycins, are briefly described. Moreover, issues associated with rifamycins are discussed as well. We expect that newly emerging rifamycins shall appear as potential tools for TB treatment in the near future.