Extended release formulations using silk proteins for controlled delivery of therapeutics

ABSTRACT

Introduction: Silk is a promising biomaterial for controlled delivery of therapeutics and has a unique protein chemistry that can be tuned to form different carrier formats. The protein has been studied for sustained release depot systems for the targeted or localized delivery of drugs.

Areas covered: An overview of natural silk proteins for controlled delivery of therapeutics is provided, with a focus on the features of silk proteins that allow them to be useful tools for controlled delivery. Recent applications of natural silk proteins as controlled delivery systems are also summarized.

Expert opinion: The versatility of silk proteins makes them desirable biomaterials for a broad range of applications for controlled delivery of both small and large molecules. Further, the degradation profile leading to peptides and amino acids provides compatibility with pH-sensitive therapeutics. While silk sericin and spider silks are under study, silk fibroin extracted from silkworms (e.g. Bombyx mori) dominates pharmaceutical studies with silk. Silk fibroin can be formed into drug delivery tools for systemic or local injections, topical and transdermal applications, and implantation; depending on the target disease and therapeutic molecule. In vitro to in vivo correlations and scale-up needs are the next steps towards clinical applications.

KEYWORDS:

• Silk
• controlled release
• drug delivery
• nanoparticles
• hydrogels
• implants
• microneedles

Article highlights

• Silk is a suitable candidate for controlled delivery of therapeutics due to controllable degradation and release kinetics, biocompatibility, all aqueous processing to maintain bioactive features of the therapeutics, and compatibility with sterilization.

• Silk has the ability to form various delivery systems, which can be applied via injections, implantation or transdermal routes.

• There is a focus on silk nanoparticles for the delivery of chemotherapeutics in order to reduce application frequency and systemic toxicity by increasing release duration, plasma circulation time and accumulation in the target area.

• Silk hydrogels are being used as injectable-sustained release depots as well as implant systems in combination with a solid support material.

• Implantable solid silk platforms such as films, wafers, foams, and reservoirs have been studied for focal delivery of chemotherapeutic molecules.

• Silk microneedles are promising transdermal delivery systems with easy fabrication techniques, controllable release, mechanical strength, and successful skin penetration.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by grants from National Institute of Health (NIH) [R01NS094218, U01EB014976].