Executive Summary : | Phagocytosis by alveolar macrophages can eliminate conventional drug encapsulated particles or cut their residence time short and thus limit the therapeutic efficacy of the drug. In pathogenic infections, targeted drug delivery to the macrophages can potentially improve the potential therapeutic outcomes. Depending on the therapeutic goal, pharmacoenginnered mediated particulate delivery approaches can be tailored to modulate particle uptake by alveolar macrophages. Macrophages are involved in the progression of a number of diseases specially mycobacterium tuberculosis (MTb). MTb pathogens use macrophages as the haven to avoid detection, extend life-span and carrier to spread infections over various tissues. Moreover, such a pathogen cell membrane comprises tightly crosslinked mycolic acids, lipids, and glycoproteins, and poses a significant barrier to drug permeability. Unfortunately, ongoing oral delivery of first‐line Tb drugs is non‐targeted, limiting bioavailability at infected sites. Design of appropriate pharmacoeginerred nanobiocontainers largely resembles and triggered to that site of infection. We hypothesize that alveolar macrophages will exhibit enhanced particulate uptake from pharmacoengineered nanoarchitectonics. Hence, drug‐loaded engineered vesicles could potentially access infected alveolar macrophages for “triggered intracellular engineered delivery strategies." In exploratory studies, we have successfully enriched and engineered nanoarchitectonics with the first-line anti-Tb drug, i.e., pyrazinamide. Here, we propose to optimize and through systemic characterization, and biological implication of the pharmacoengineered nanoarchitectonics not only to enhance particle uptake capability but also to improve their therapeutic efficacy for potential future translational medicine.
Thus, application of pharmacoenginnering strategies such as particle engineering, targeted delivery/device engineering platforms, surface engineering, biomedical engineering, etc., with latest experimental approaches are relevant to that context in conjunction with both qualitative and quantitative methods from macrophage biology, biopharmaceutics, and molecular pharmacoengineering perspectives to solve problems in drugs and existing drug therapies in order to facilitate novel engineered deliverables both for human and veterinary health. Such, pharmacoengineered based delivery devices are also currently expanding its arena due to their wide acceptability, site-specificity, sustainability, biodegradability biocompatibility and superior bioavailability. |