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Bioengineered Silk-Based Delivery Systems

Silk-based drug delivery systems are studied to exploit the all-water processing, the ability to regulate beta sheet (crystalline) content for control of lifetime in vivo (days to years), to control medical device format (e.g., coating, fibers, tablets, gels, etc.), to deliver small or large molecules that are hydrophilic or hydrophobic, and to exploit the stabilization influence of silk on labile compounds. We approach the challenge from both a fundamental design approach (genetically engineered block copolymers) to direct delivery systems from reprocessed silkworm silk. In vitro and in vivo studies are conducted to understand and optimize the various systems.

Macromol Biosci. 2014 May 30. doi: 10.1002/mabi.201400113
Gene delivery research has gained momentum with the use of lipophilic vectors that mimic viral systems to increase transfection efficiency. Maintaining cell viability with these systems remains a major challenge. Therefore, biocompatible biopolymers that are designed by combining non-immunological viral mimicking components with suitable carrier are explored to address these limitations. In the present study, dragline silk recombinant proteins are modified with DNA condensing units and the proton sponge endosomal escape pathway is utilized for enhanced delivery. Transfection efficiency in a COS-7 cell line is enhanced compared to lipofectamine and polyethyleneimine (PEI), as is cell viability.

Adv Funct Mater. 2013 Jan 7;23(1):58-65
Standard care for early stage breast cancer includes tumor resection and local radiotherapy to achieve long-term remission. Systemic chemotherapy provides only low locoregional control of the disease; therefore, we describe self-assembling silk hydrogels that can retain and then deliver doxorubicin locally. Self-assembling silk hydrogels show no swelling, are readily loaded with doxorubicin under aqueous conditions and release drug over 4 weeks in amounts that can be fine-tuned by varying the silk content. Thus, silk hydrogels are well suited for the local delivery of chemotherapy and provide a promising approach to improve locoregional control of breast cancer.

Adv Funct Mater. 2013 Feb 18;23(7):854-861
Effective treatment of infections in avascular and necrotic tissues can be challenging due to limited penetration into the target tissue and systemic toxicities. Controlled release polymer implants have the potential to achieve the high local concentrations needed while also minimizing systemic exposure. Silk biomaterials possess unique characteristics for antibiotic delivery including biocompatibility, tunable biodegradation, stabilizing effects, water-based processing and diverse material formats. The capability of silk antibiotic carriers to sequester, stabilize and then release bioactive antibiotics represents a major advantage over implants and pumps based on liquid drug reservoirs where instability at room or body temperature is limiting. (A) Silk fibers after immersion in a 20 mg mL-1 rifampicin in methanol solution overnight, rinsing in distilled water and drying. (B) Representative sample agar plate showing zone of inhibition in S. aureus lawns produced by rifampicin-releasing silk fibers. (C) Representative sample agar plate showing the zones of inhibition in S. aureus lawns produced by rifampicin-releasing silk film.