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Amit Mirani

Title: Polyphenols loaded vaginal microbicide: A novel strategy for prevention of HIV transmission

Amit Mirani

Institute of Chemical Technology, India

Biography

Amit is a Senior Research Fellow pursuing his Ph.D. (Tech.) degree in Pharmaceutics with Prof. Vandana B. Patravale in Department of Pharmaceutical Sciences and Technology at Institute of Chemical Technology (ICT), Mumbai. Amit is currently working on “Nanotherapeutics for Prophylaxis of HIV” sponsored by DBT-ICMR agency. He has 2 international publications and has co-authored 3 book chapters in “Pharmaceutical Product Development” published by Taylor & Francis Inc. He has also won 3 Best Poster Awards in International Conferences.  

Abstract

The unprotected sexual intercourse associated HIV is one of the most serious challenges to public health all over the world. According to recent reports, sexual transmission is the predominant mode of HIV transmission. This rate could be declined by a prophylactic strategy using a microbicide. Several prophylactic microbicides, when tested clinically, have failed to show efficacy and exert poor adherence which is mainly attributed to the emergence of drug resistance, severe adverse effects. Thus, there is a need for identification of safe and effective drug candidates that can prevent early stage transmission HIV-1 via unprotected sexual intercourse. Polyphenols are the naturally occurring secondary metabolites with wide therapeutic activities viz., anti-viral, anti-cancer, anti-aging, etc. However, the polyphenols which act at early stage gp120-CD4 binding inhibition are not yet identified. With this understanding, a suitable class of naturally occurring polyphenols was subjected to in silico screening (molecular docking and dynamics simulation studies) using homology model of gp12-CD4 binding. Amongst the tested polyphenols, punicalagin exhibited superior gp120-CD4 binding affinity due to its stable hydrophobic interactions with residues Asp368 and Trp427at deeper site in the Phe43 cavity and the same was confirmed by in vitro cell line study (IC50=0.237µM) and hence it was considered as a lead. With this proof, Punicalagin rich P. granatum extract loaded novel microbicide gel was developed and optimised for efficient delivery via the rectal/vaginal route. The P. granatum extract loaded nanomicrobicide gel exhibited 40 times higher anti HIV activity as compared to tenofovir disoproxil fumarate. Further, it showed mild but acceptable irritation score when tested in rabbits for consecutive 14 days application. Thus, the novel natural nanomicrobicide ensured enhanced efficacy and acceptable safety proving the potential of polyphenols as gp120-CD4 binding inhibitors for prevention of HIV transmission via unprotected sexual intercourse.

Audience will learn:
•HIV prophylaxis is a niche area where the research still is in clinical phase. The lack of effective formulation strategy is the major concern for the success of HIV prophylaxis. The proposed work would help the audience to understand the role of key excipients with inherent therapeutic effect and herbal entities to provide complete HIV-1 prophylaxis    
•The proposed nanotechnology could be utilised for different hydrophilic/lipophilic entities for both vaginal/rectal delivery
•Encourage the audience to adapt reverse pharmacology for life-threatening diseases.