Men who sleep with men are more severely affected by HIV infection than any other group in the US, representing the vast majority of new infections each year. Pre-exposure prophylaxis (PrEP), the only FDA-approved HIV prevention method, is effective in reducing infection only if patients take their medicines as prescribed. Unfortunately, recent experience with orally administered PrEP indicates the majority of patients do not take their medications regularly. In this research program, a nanotechnology-based pharmaceutical foam administered rectally once a week will be developed to prevent the establishment of permanent HIV infection. Anti-HIV drugs will be released from nanoparticles that are absorbed and stay in colonic and rectal tissue for a week treating early viral exposure locally. Two groups of therapeutic agents, suppressive antiretrovirals and TRAP (therapeutic reclamation of apoptotic proficiency) agents, will be investigated in parallel. The proposed research will accomplish its objectives by first formulating rectally administered foams that spread drug- containing nanoparticles throughout the rectum and colon. The program will next develop nanoparticles that are taken up and remain locally for a week in rectal and colonic tissues. For each drug, multiple groups of nanoparticles will be engineered to have different delays and release times in order to achieve effective drug exposure in the tissue for up to a week. Finally, foams containing the engineered nanoparticles will be evaluated preclinically. This new treatment option, known as mucosal PrEP, may drastically reduce drug dosages and frequency of administration resulting in fewer side effects and increased patient compliance.

Public Health Relevance

In this research program, a nanotechnology-based pharmaceutical foam administered rectally once a week will be developed to prevent the establishment of permanent HIV infection. Anti-HIV drugs will be released from nanoparticles that are absorbed and stay in colonic and rectal tissue treating early viral exposure locally for a week. This new treatment option, known as mucosal Pre-exposure prophylaxis (PrEP), may drastically reduce drug dosages and frequency of administration resulting in fewer side effects and increased patient compliance.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI117776-04
Application #
9419761
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Turpin, Jim A
Project Start
2015-02-01
Project End
2020-01-31
Budget Start
2018-02-01
Budget End
2020-01-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Rutgers University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
001912864
City
Piscataway
State
NJ
Country
United States
Zip Code
Heon Lee, In; Palombo, Matthew S; Zhang, Xiaoping et al. (2018) Design and evaluation of a CXCR4 targeting peptide 4DV3 as an HIV entry inhibitor and a ligand for targeted drug delivery. Eur J Pharm Biopharm :
Samizadeh, Mahta; Zhang, Xiaoping; Gunaseelan, Simi et al. (2016) Colorectal delivery and retention of PEG-Amprenavir-Bac7 nanoconjugates--proof of concept for HIV mucosal pre-exposure prophylaxis. Drug Deliv Transl Res 6:1-16
Gao, Yu; Jin, Biyu; Shen, Weiyu et al. (2016) China and the United States--Global partners, competitors and collaborators in nanotechnology development. Nanomedicine 12:13-9
Pinkerton, Nathalie M; Gindy, Marian E; Calero-DdelC, Victoria L et al. (2015) Single-Step Assembly of Multimodal Imaging Nanocarriers: MRI and Long-Wavelength Fluorescence Imaging. Adv Healthc Mater 4:1376-85
Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha et al. (2015) Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment. J Control Release 219:669-680
Tang, Christina; Xiao, Edward; Sinko, Patrick J et al. (2015) Responsive foams for nanoparticle delivery. Colloids Surf B Biointerfaces 133:81-7