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利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 高度疏水药物与无毒、非免疫原性和明确界定的载体的增溶仍然是药学科学的主要障碍。合成了基于聚(2-恶唑啉)的两亲性双嵌段和三嵌段共聚物，并将其用于增溶紫杉醇(PTX)和其他水不溶性药物。用荧光探针芘探测水中的聚合物胶束，观察到该探针的异常高极性微环境。这与PTX在配方中45wt.%的活性药物的超大载药量以及由此得到的配方的高水溶性不谋而合。制剂的物理化学性质、制备工艺、冻干稳定性、低毒和免疫原性表明，聚(2-恶唑啉)S是一种很有前途的具有挑战性的药物载体。此外，我们证明了PTX是完全有效的，与商业胶束制剂相比，它提供了更好的肿瘤抑制。

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.