Stabilization and Sustained Release of HIV Inhibitors by Encapsulation in Silk Fibroin Disks
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Topical microbicides have the potential to provide effective protection against sexual transmission of HIV. Challenges in developing microbicides include their application in resource-poor settings with high temperatures and a lack of refrigeration, and low user adherence to a rigorous daily regimen. Several protein-based HIV inhibitors show great promise as microbicides, being highly specific and not expected to lead to resistance that would affect the efficacy of current antiretroviral treatments. We show that four potent protein HIV inhibitors, 5P12-RANTES, 5P12-RANTES-L-C37, Grft, and Grft-L-C37 can be formulated into silk fibroin (SF) disks and remain functional for 14 months at 25, 37, and 50 °C. These HIV inhibitor-encapsulated SF disks show excellent inhibition properties in PBMC and in human colorectal and cervical tissue explants, and do not induce inflammatory cytokine secretion. Further, the SF provides a mechanically robust matrix with versatile material formats for this type of application. Finally, a formulation was developed to allow sustained release of functional Grft for 4 weeks at levels sufficient to inhibit HIV transmission. This work establishes the suitability of HIV inhibitor-encapsulated SF disks as topical HIV microbicides that can be further developed to allow easy insertion for extended protection.
Date Issued
2017-05-22
Date Acceptance
2017-05-22
Citation
ACS BIOMATERIALS SCIENCE & ENGINEERING, 2017, 3 (8), pp.1654-1665
ISSN
2373-9878
Publisher
American Chemical Society
Start Page
1654
End Page
1665
Journal / Book Title
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume
3
Issue
8
Copyright Statement
© 2017 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Biomaterials Science and Engineering, after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acsbiomaterials.7b00167
Sponsor
National Institutes of Health
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000407874600021&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
F105GRA084
Subjects
Science & Technology
Technology
Materials Science, Biomaterials
Materials Science
silk fibroin
drug stabilization
sustained release
HIV microbicide
SPI2-RANTES
Griffithsin
IMMUNODEFICIENCY-VIRUS TYPE-1
IN-VIVO
INTRAVAGINAL RING
ENTRY INHIBITOR
HIGHLY POTENT
ENV CLONES
GRIFFITHSIN
PROPHYLAXIS
MICROBICIDE
INFECTION
Publication Status
Published