NANO-FORMULATION OF ANTIMICROBIAL PEPTIDES FOR THE MANAGEMENT OF BACTERIAL INFECTIONS

近年来，深入研究的重点是寻找抗菌疗法。抗菌肽 (AMP) - 由 12-45 个氨基酸组成的阳离子肽，已成为传统抗生素的有前景的替代品。 AMP可以阻止细菌增殖，因此细菌无法对它们产生任何抵抗力。尽管AMP被认为是一类新型抗生素，也是一种很好的替代品，但在临床领域使用之前还需要解决一些问题。即使在到达感染部位之前，AMP 也很容易被人体内存在的蛋白水解酶降解。因此，需要设计 AMP 的递送载体，以保护它们免于早期降解并确保它们直接递送到感染部位。通过我们对聚合物纳米颗粒/水凝胶技术的广泛研究，我们建议使用聚合物纳米颗粒/纳米凝胶/水凝胶作为AMPs纳米载体。聚合物可以通过多种方式进行工程设计，使其无毒、可以轻松封装分子或大分子并且可以在人体内代谢。负载 AMP 的聚合物纳米颗粒将针对特定的管理途径进行进一步修改，这将提高其临床疗效。为了用于呼吸输送，聚合物纳米颗粒将涂有天然粘膜粘附聚合物并通过雾化输送。为了治疗感染性伤口，它们将被包裹在基于纤维素纳米晶体的水凝胶中并用作伤口敷料。我们假设负载 AMP 的聚合物纳米颗粒可以成功克服抗生素耐药菌株引起的感染。在临床中使用负载 AMP 的纳米颗粒可能会减少我们对日常使用的传统抗生素的依赖，并防止细菌耐药性的发展。它将改善患者的整体健康状况并降低治疗成本。该项目将提供一个框架，以了解选定的抗菌肽和聚合物纳米颗粒/水凝胶的相互作用、肽封装和释放动力学的功效及其生物特性。

In recent years, intensive research has focused on finding antimicrobial therapies. Antimicrobial peptides (AMPs) - cationic peptides consisting of 12-45 amino acids, have emerged as promising alternatives to conventional antibiotics. AMPs can stop bacteria from proliferation and thus bacteria could not develop any resistance to them. Though AMPs are regarded as a new class of antibiotics and also a good alternative, several problems need to be addressed before their use in the clinical field. The AMPs are easily prone to degradation by proteolytic enzymes present in human body even before reaching the infected site. As a result, there is a need to engineer delivery carriers for AMPs to protect them from early degradation and ensuring their direct delivery to the infected sites. With our extensive research on polymer nanoparticles/hydrogels technology, we suggest the use polymer nanoparticles/nanogels/hydrogels as AMPs nanocarriers. Polymers can be engineered in a multitude of ways such that they are non-toxic, can easily encapsulate molecules or macromolecules and can be metabolized in human body. The AMPs-loaded polymer nanoparticles will be further modified for specific management routes which will improve their clinical efficacy. In order to be used for respiratory delivery, polymer nanoparticles will be coated with natural muco-adhesive polymers and delivered via nebulisation. For the treatment of infectious wounds, they will be entrapped in cellulose nanocrystal based hydrogels and used as wound dressings. We hypothesize that polymer nanoparticles loaded with AMPs can successfully overcome infections caused by antibiotic-resistant bacterial strains. The use of AMPs-loaded nanoparticles in clinics can potentially reduce our reliance on conventional antibiotics that are used on a daily basis and prevent progress of bacterial resistance. It will improve the overall health of patients and also decrease treatment cost. This project will provide a framework in understanding the interactions of selected antimicrobial peptides and polymer nanoparticles/hydrogels, efficacy of peptide encapsulation and release kinetics, and their biological properties.