Biodegradable and Biocompatible Chitosan-Protein Nanoparticles in Drug Delivery

纳米粒子疗法以天然聚合物和合成聚合物与水溶性聚合物为基础，为改善抗癌药物的输送提供了新的途径。这有助于药物的溶解，通过长循环增加治疗过程，并通过实现渗透性和滞留效果增强对肿瘤的摄取。在用于药物递送系统的天然阳离子聚合物中，壳聚糖是一种生物相容性、可生物降解性和多功能的聚合物，因此在纳米生物医学技术领域引起了人们的极大兴趣。壳聚糖及其衍生物作为药物给药工具具有安全使用所需的性能。利用壳聚糖及其衍生物作为药物载体的主要目的是提高治疗药物(多肽、蛋白质、抗原和质粒DNA)在体内的生物利用度。然而，壳聚糖只溶于酸性溶液，不能在中性pH条件下溶解，这给药物载体的制备带来了很大的困难。为了提高壳聚糖的溶解性和亲和力，需要对聚合物结构进行修饰。壳聚糖-蛋白质偶联将增加聚合物在生理pH中的溶解度，并将显著提高壳聚糖在药物输送系统中的效率。*在该方案中，不同尺寸(15、50、100和200 KDa)的壳聚糖纳米颗粒将与不同的转运蛋白，如人和牛血清白蛋白和β-乳球蛋白进行偶联。由于所选蛋白质的疏水性不同，壳聚糖-蛋白质纳米粒对亲水和疏水药物具有更强的选择性。采用多种光谱方法和热力学分析，结合透射电子显微镜、扫描电子显微镜、原子力显微镜、共振光散射(RLS)/Zeta电位和分子模拟等手段，对阿霉素、柔红霉素、伊达阿比星、他莫昔芬、4-氢三苯氧胺和依多昔芬等几种抗癌药物与壳聚糖蛋白纳米胶囊进行包埋。评价聚合物大小和相对分子质量对药物纳米粒包封率的影响。将监测药物的控制和释放，并确定每种结合物在药物输送中的效率。*这项研究很重要，因为载体和药物的非共价结合是决定包封率和药物释放效率的最重要的分子方面之一。所产生的信息将有助于更合理的壳聚糖设计，解决药物传递系统中的问题，同时将推动新的新兴技术走向临床研究。该计划涉及多个学科，为我们的学生提供了与药物输送相关的重要知识，使他们能够在就业市场上具有很强的竞争力。

Nanoparticle therapeutics, based on natural and synthetic polymers with water-soluble polymers, offer new routes to improve cancer drug delivery. This aids the drug solubility, increases the therapeutic process through long circulation and enhances the uptake into tumors by achieving the permeability and retention effect. Among natural cationic polymers used in drug delivery systems, chitosan has attracted a major interest in the nanobiomedical technology sector since it is a biocompatible, biodegradable and versatile polymer. Chitosan and its derivatives have the desired properties for safe use as pharmaceutical drug delivery tools. The principal interest in using chitosan and its derivatives as a pharmaceutical carrier is to enhance the bioavailability of therapeutic drugs (peptides, proteins, antigens and plasmid DNAs) in vivo. However, chitosan is only soluble in acidic solution and not at neutral pH, which causes a major problem for drug-carrier formulation. Modifications of polymer structure are needed, in order to increase chitosan solubility and affinity. Chitosan-protein conjugation will increase polymer solubility in physiological pH and will enhance markedly chitosan efficiency in a drug delivery system.****In this proposal chitosan nanoparticles of different sizes (15, 50, 100 and 200 KDa) will be conjugated with different transporter proteins, such as human and bovine serum albumins and beta-lactoglobulin. Since selected proteins are different in hydrophobicity, chitosan-protein nanoparticles will be more selective towards hydrophilic and hydrophobic drugs. Encapsulation of several anticancer drugs such as doxorubicin, daunorubicin, idarubicin, tamoxifen, 4-hydrotamoxifen and endoxifen with chitosan-protein nanocapsules will be carried out using multiple spectroscopic methods and thermodynamic analysis in combination with TEM, SEM, AFM microscopic imaging, resonance light scattering (RLS)/zeta potential and molecular modeling. The effects of polymer size and molecular weight on drug-nanoparticle encapsulation will be evaluated. Control and release of the drug will be monitored and the efficiency of each conjugate in drug delivery will be determined.****This study is important, as non-covalent association of carrier and drug is one of the most significant molecular aspects that dictate the encapsulation efficacy and drug release efficiency. The generated information will facilitate a more rational chitosan design, resolving problems in drug delivery system; meanwhile it will advance novel and emerging technologies toward clinical investigation. The proposal is multidisciplinary and provides our students with important knowledge related to drug delivery, enabling them to be highly competitive in the job market.******