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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.