Sustained release silk fibroin discs: Antibody and protein delivery for HIV prevention

Abstract

With almost 2 million new HIV infections worldwide each year, the prevention of HIV infection is critical for stopping the pandemic. The only approved form of pre-exposure prophylaxis is a costly daily pill, and it is recognized that several options will be needed to provide protection to the various affected communities around the world. In particular, many at-risk people would benefit from a prevention method that is simple to use and does not require medical intervention or a strict daily regimen. We show that silk fibroin protein can be formulated into insertable discs that encapsulate either an antibody (IgG) or the potent HIV inhibitor 5P12-RANTES. Several formulations were studied, including silk layering, water vapor annealing and methanol treatment to stabilize the protein cargo and impact the release kinetics over weeks. In the case of IgG, high concentrations were released over a short time using methanol treatment, with more sustained results with the use of water vapor annealing and layering during device fabrication. For 5P12-RANTES, sustained release was obtained for 31 days using water vapor annealing. Further, we show that the released inhibitor 5P12-RANTES was functional both in vitro and in ex vivo colorectal tissue. This work shows that silk fibroin discs can be developed into formidable tools to prevent HIV infection.

Silk Fibroin as a Functional Biomaterial for Drug and Gene Delivery

“…In a novel study conducted by Yavuz et al [27] SF was formulated into insertable discs that can encapsulate either IgG antibody or human immunodeficiency virus (HIV) inhibitor 5P12-RANTES. Three different formulations were prepared by SF layering, water vapor annealing, and methanol treatment.…”

“…Hence, loading the biological therapeutics into a compatible polymer can increase their stability and consequently their half-life [22]. Moreover, incorporating the APIs into a natural biocompatible protein such as SF has multiple advantages e.g., preserving the API [23], improving the mechanical properties of the formulation [6], modifying drug release kinetics [24,25,26,27], enhancing cell adhesion [16], and compatibility with blood components [25]. The versatility of SF protein processing and formulating methods allows the preparation of a wide range of drug carriers with different sizes and morphologies using unmodified or engineered SF (Figure 1).…”

Efficacy of silk fibroin biomaterial vehicle for in vivo mucosal delivery of Griffithsin and protection against HIV and SHIV infection ex vivo

“…We developed methodology for generating silk fibroin discs and optimized conditions for encapsulating them with anti-HIV agents for sustained release [22,27]. In this study, we enhanced the silk fibroin delivery discs with the higher payload of inhibitors.…”

“…Aside from its usage in some cases for sutures, the main FDA approved clinical use of silk fibroin is the SERI surgical scaffold, a surgical mesh for abdominal wall and breast reconstruction [25,26]. SF formulations can encapsulate several anti-HIV proteins, be stable for more than one year, and mediate quick release or sustained release over the course of one month [22,27,28]. Considering the need for sustained drug delivery of PrEP candidates at mucosal sites, SF provides an innovative platform that can be affordably produced, safely administered, and is effective against HIV transmission.…”

The influence of thermal treatments on the secondary structure of silk fibroin scaffolds and their interaction with fibroblasts

“…It has also long been used in surgical sutures, which causes no significant side effects. Recently, many reports have described the use of silk fibroin-based biomaterials in tissue engineering (Kawakami et al, 2011;Lee et al, 2017;Luetchford, Chaudhuri & De Bank, 2020) and drug delivery systems (Mao et al, 2018;Cheng et al, 2020) and as substrates for anticoagulants (Tamada, 2003) and anti-HIV materials (Yavuz et al, 2019). Regenerated silk fibroin can be fabricated into various forms such as films (Aznar-Cervantes et al, 2019), hydrogels (Zuluaga-Vélez et al, 2019), sponges (Tamada, 2005), resins (Kaneko et al, 2012), fibers (Zhang et al, 2016) and nanofibers (Kopp et al, 2020).…”