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

用于治疗 HIV/HCV 混合感染的抗病毒肽纳米复合物 (APN)

• 批准号: 8360243
• 负责人: LARISA Y POLUEKTOVA
• 金额: $ 23.67万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360243
• 关键词: Drug Formulations; Fluorescence; Freeze Drying; Funding; Grant; HIV; Hepatitis C virus; Infection; Micelles; National Center for Research Resources; Nebraska; Paclitaxel; Peptides; Pharmaceutical Preparations; Pharmacologic Substance; Polymers; Preparation; Principal Investigator; Property; Pyrenes; Research; Research Infrastructure; Resources; Science; Source; Toxic effect; United States National Institutes of Health; Viral; Water; base; copolymer; cost; immunogenicity; nanomedicine; tumor; water solubility

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.

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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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。