Protein-Based Drug-Delivery Materials

Abstract

There is a pressing need for long-term, controlled drug release for sustained treatment of chronic or persistent medical conditions and diseases. Guided drug delivery is difficult because therapeutic compounds need to survive numerous transport barriers and binding targets throughout the body. Nanoscale protein-based polymers are increasingly used for drug and vaccine delivery to cross these biological barriers and through blood circulation to their molecular site of action. Protein-based polymers compared to synthetic polymers have the advantages of good biocompatibility, biodegradability, environmental sustainability, cost effectiveness and availability. This review addresses the sources of protein-based polymers, compares the similarity and differences, and highlights characteristic properties and functionality of these protein materials for sustained and controlled drug release. Targeted drug delivery using highly functional multicomponent protein composites to guide active drugs to the site of interest will also be discussed. A systematical elucidation of drug-delivery efficiency in the case of molecular weight, particle size, shape, morphology, and porosity of materials will then be demonstrated to achieve increased drug absorption. Finally, several important biomedical applications of protein-based materials with drug-delivery function-including bone healing, antibiotic release, wound healing, and corneal regeneration, as well as diabetes, neuroinflammation and cancer treatments-are summarized at the end of this review.

Keywords: collagen; controlled release; drug delivery; elastin; keratin; protein biopolymer; silk.

Figure 1

Various proteins and their possible sources under research for drug-delivery applications: (A) silk from Bombyx mori cocoons; (B) resilin from dragonfly; (C) collagen from fish scales; (D) keratin from goat hairs. These proteins can be fabricated into various drug-delivery vehicles such as films, sponges, gels, fibers, nanoparticles and microneedles. (Reproduced with permission from Reference [7,8,10,11], ACS Publications and Elsevier.)

Figure 2

Preparation for the magnetic human elastin-like polypeptide (HELP) microparticles with various controlled drug-delivery applications. (Reproduced with permission from Reference [72], John Wiley and Sons).

Figure 3

Microfluidic schematic for producing collagen microparticles. (Reproduced with permission from Reference [73], The Royal Society of Chemistry).

Figure 4

Schematic of silk microneedle fabrication for drug delivery. (Reproduced with permission from Reference [78], John Wiley and Sons).

Figure 5

(A) SDS-PAGE analysis of silk with different degumming times (10 min, 30 min, 60 min and 90 min); (B) Cumulative release of rifampicin from silk gel films capped with a single layer of silk prepared using varied degumming times. (Reproduced with permission from Reference [27], John Wiley and Sons).

Figure 6

(A) Schematic of a magnetic nanoparticle-based drug-delivery system; (B) Plot of the magnetic coercivity (Hc) vs. the size of particle for drug delivery. (Reproduced with permission from Reference [98], Elsevier, and Reference [99], The Royal Society of Chemistry).

Figure 7

Micrographs of PRINT particles varying in both size and shape. The scale bars for (A) is 20 μm; (B–D) is 1 μm. (Reproduced with permission from Reference [103], Copyright (2008) National Academy of Sciences, U.S.A.).