EAPSI: Engineering Nanocarriers to Penetrate Colorectal Tissue as Platforms for HIV Prevention

Nelson Antoinette G, Far Rockaway NY

Investigators

Abstract

Without a cure or vaccine for the Human Immunodeficiency Virus (HIV), one of the most promising ways to slow down its spread is by focusing on prevention. In the development of HIV prevention strategies, patient adherence has been a major limitation. One factor that may cause poor adherence is prescribed drug regimen that require frequent dosing. In addition, individuals may be burdened with unwanted side effects that result from large doses and systemic toxicity. Nanotechnology is of significant interest to help address these concerns. This project will be conducted in collaboration with Dr. Xing-Jie Liang at the National Center for Nanoscience and Technology of China. As an expert in nanomedicine, Dr. Liang will provide guidance on the design and characterization of dendrimers, a form of branch-like nano-carriers, to be administered to the colorectum as drug delivery systems for HIV prevention. This work will establish greater insights into nano-scale drug delivery and develop the framework to produce more safe, convenient and effective pharmaceutical interventions. Exposure to HIV through unprotected sexual activity remains the primary cause of transmission worldwide. Currently, the only approach approved by the Federal Drug Administration (FDA) for HIV prevention is orally administered pre-exposure prophylaxis (PrEP) in the form of a combinational drug product. With oral PrEP, relatively large dosages are required to achieve effective concentrations in mucosal tissues. Additionally, the entire body is being exposed to antiretrovirals, raising concerns of systemic toxicity. Together with a strict once-a-day dosing regimen, these conditions contribute to overall poor patient adherence behaviors that may result in ineffectiveness of treatment. Therefore, significant research is currently being conducted to develop effective, safe, and long-acting PrEP formulations. Based on the unique physicochemical properties of nanomaterials, they show great promise in their ability to aid in the development of these applications. Dr. Xing-Jie Liang is an expert in nanomedicine with extensive experience in drug delivery and active cell and tissue targeting to enhance drug safety and efficacy. The project will be guided by the following aims: 1) engineer dendrimers labeled with established cell penetrating peptides; 2) characterize dendrimers by imaging and spectral analysis and 3) investigate cellular uptake in intestinal cells by flow cytometry and confocal microscopy. The completion of this work will establish a deeper understanding of nanoengineering and cell targeting techniques to potentially serve as interventions for HIV and within other areas of biomedical research. This award, under the East Asia and Pacific Summer Institutes program, supports summer research by a U.S. graduate student and is jointly funded by NSF and the Ministry of Science and Technology of China.