Imperial College London
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DrCarolinaHerrera

Faculty of Medicine, Department of Infectious Disease

Honorary Senior Research Fellow
 
 
 
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Contact

 

carolina.herrera

 
 
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Location

 

460 (Shattock Group)Medical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Crakes:2020:10.1002/jia2.25628,
author = {Crakes, KR and Herrera, C and Morgan, JL and Olstad, K and Hessell, AJ and Ziprin, P and LiWang, PJ and Dandekar, S},
doi = {10.1002/jia2.25628},
journal = {Journal of the International AIDS Society},
title = {Efficacy of silk fibroin biomaterial vehicle for in vivo mucosal delivery of Griffithsin and protection against HIV and SHIV infection ex vivo},
url = {http://dx.doi.org/10.1002/jia2.25628},
volume = {23},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - INTRODUCTION: The majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention. METHODS: We formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge. RESULTS: Effective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota. CONCLUSIONS: We demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two
AU  - Crakes,KR
AU  - Herrera,C
AU  - Morgan,JL
AU  - Olstad,K
AU  - Hessell,AJ
AU  - Ziprin,P
AU  - LiWang,PJ
AU  - Dandekar,S
DO  - 10.1002/jia2.25628
PY  - 2020///
SN  - 1758-2652
TI  - Efficacy of silk fibroin biomaterial vehicle for in vivo mucosal delivery of Griffithsin and protection against HIV and SHIV infection ex vivo
T2  - Journal of the International AIDS Society
UR  - http://dx.doi.org/10.1002/jia2.25628
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33073530
UR  - http://hdl.handle.net/10044/1/83870
VL  - 23
ER  -
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