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

近年来，密集的研究集中在寻找抗菌疗法上。抗菌肽（Antimicrobial peptides，AMP）是一种由12-45个氨基酸组成的阳离子肽，是传统抗生素的理想替代品。抗菌肽可以阻止细菌增殖，因此细菌不会对它们产生任何抗性。抗菌肽是一种新型的抗生素，也是一种很好的替代药物，但在其应用于临床之前还需要解决一些问题。AMP甚至在到达感染部位之前就容易被人体中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。通过对聚合物纳米粒子/水凝胶技术的深入研究，我们提出了将聚合物纳米粒子/纳米凝胶/水凝胶作为抗菌肽纳米载体的设想。聚合物可以以多种方式工程化，使得它们是无毒的，可以容易地封装分子或大分子，并且可以在人体内代谢。载AMP的聚合物纳米颗粒将被进一步修饰以用于特定的管理途径，这将提高其临床疗效。为了用于呼吸递送，聚合物纳米颗粒将用天然粘膜粘附聚合物涂覆并通过雾化递送。对于感染性伤口的治疗，它们将包埋在基于纤维素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地克服由耐药性细菌菌株引起的感染。在临床中使用载AMP的纳米颗粒可能会减少我们对日常使用的常规抗生素的依赖，并防止细菌耐药性的发展。这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，以及它们的生物学特性。

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.