ANTI-VIRAL PEPTIDE NANOCOMPLEXES (APN) FOR TREATMENT OF HIV/HCV CO-INFECTION

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 为子项目列出的总成本可能 表示子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 用无毒、无免疫原性和明确定义的载体溶解高度疏水性药物仍然是药学科学中的主要障碍。制备了基于聚（2-恶唑啉）的两亲性二嵌段和三嵌段共聚物，并将其用于紫杉醇（PTX）和其他水不溶性药物的增溶。以芘为荧光探针探测水中的聚合物胶束，观察到了异常的高极性微环境。这与45重量%的PTX的非常大的负载容量相一致制剂中的活性药物以及所得制剂的高水溶性。制剂的物理化学性质、制备的容易性和冻干后的稳定性、低毒性和免疫原性表明聚（2-恶唑啉）是用于递送高度挑战性药物的有希望的候选物。此外，我们证明了PTX是完全活性的，并且与商业胶束制剂相比提供了上级肿瘤抑制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well defined remains a major obstacle in pharmaceutical sciences. Well-defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45 wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.