Silk-based delivery systems of bioactive molecules

Department of Biomedical Engineering, Tufts University, Medford, MA 02155, USA.
Advanced drug delivery reviews (Impact Factor: 15.04). 03/2010; 62(15):1497-508. DOI: 10.1016/j.addr.2010.03.009
Source: PubMed


Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed.

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    • "In the past years, the surface modification of silk fibroin (SF) fibers by chemically bound polymers with tailored surface properties has been widely considered as a new powerful method to substantially improve some intrinsic fiber properties such as slow biodegradation, good mechanical properties, and favorable processability in combination with biocompatibility [1] [2] [3] [4] [5] [6] [7] [8]. Bombyx mori silk, one of the most pervasive natural polymer, the most characterized silkworm silk, has been regarded as an attractive material with different biomedical and biotechnological applications [8] [9] [10]. "
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    ABSTRACT: In this study, silk fibroin surface containing hydroxyl and aminogroups was firstly modified using a polymerizable coupling agent 3-(trimethoxysilyl) propyl methacrylate (MPS), in order to induce vinyl groups onto the fiber surface. The reversible addition-fragmentation chain transfer (RAFT)-mediated polymerization of methyl methacrylate (MMA) and tributylsilyl methacrylate (TBSiMA) through the immobilized vinyl bond on the silk fibroin surface in the presence of 2-cyanoprop-2-yl dithiobenzoate (CPDB) as chain-transfer agent and 2,2'-azobis(isobutyronitrile) (AIBN) as initiator was conducted in toluene solution at 70°C for 24h. The structure and properties of the modified fiber were characterized by Fourier Transform Infrared Spectroscopy, (13)C, (29)Si Nuclear Magnetic Resonance (NMR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS), confirming the presence of the coupling molecule and the methacrylate groups onto the silk fibroin fiber surface. Molecular weight distributions were assessed by triple detection size exclusion chromatography (TD-SEC) in order to verify the livingness of the polymerization. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · Mar 2015 · Materials Science and Engineering C
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    • "Silks can be classified as mulberry and nonmulberry, which are produced by domesticated Bombyx mori (Bombycidae family) and wild silkworm species, respectively. Bombyx mori silk-based biomaterials have been extensively used for tissue engineering scaffolds [5] [6], biomedical devices [7] [8] and for drug release [9]. Of the various wild silkworms, Antheraea pernyi and Antheraea yamamai are relatively common species that belong to the Saturniidae family (order Lepidoptera, phylum Arthropoda). "
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    ABSTRACT: Degradation behavior is very important in the field of silk-based biomaterials. Mulberry and nonmulberry silk fibroins are structurally and functionally distinguishable; however, no studies have examined the differences in the degradation behaviors of silk materials from various silkworm species. In this study, Ca(NO3)2 was used as a uniform solvent to obtain regenerated mulberry and nonmulberry (Antheraea pernyi and Antheraea yamamai) silk fibroin (SF) solutions, and the degradation behaviors of various SF scaffolds were examined. In vitro and in vivo results demonstrated that regenerated mulberry SF scaffolds exhibited significantly higher mass loss and free amino acid content release than did nonmulberry SF scaffolds. The differences in the primary structures and condensed structures between mulberry and nonmulberry SF contributed to the significant difference in degradation rates, in which the characteristic (–Ala–)n repeats, compact crystal structure and high α-helix and β-sheet contents make nonmulberry SF more resistant than mulberry SF to enzymatic degradation. Moreover, the Antheraea pernyi and Antheraea yamamai SFs possess similar primary structures and condensed structures, although a slight difference in degradation was observed; this difference might depend on the differences in molecular weight following the regeneration process. The results indicate that the original sources of SF significantly influence the degradation rates of SF-based materials; therefore, the original sources of SF should be fully considered for preparing tissue engineering scaffolds with matched degradation rates.
    Full-text · Article · Feb 2015 · Biomedical Materials
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    • "Several properties of silk, such as mechanical characteristics , solubility, and biodegradability, can be controlled by manipulating silk's structure. Silk proteins have been genetically engineered in a variety of host systems [7]. Furthermore , multi-component systems of silk fibroin blended with various substances have been produced [8] [9]. "
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    ABSTRACT: Silk fibroin demonstrates great biocompatibility and is suitable for many biomedical applications, including tissue engineering and regenerative medicine. Current research manipulates the physico-chemical properties of fibroin, reflecting on its biocompatibility. Regenerated silk fibroin was modified by in vitro enzymatic phosphorylation and casted into films. Films were produced by blending at several ratios the phosphorylated and un-phosphorylated fibroin solutions. Fourier transform infra-red spectroscopy (FTIR) pointed out on the specific P-OH vibration peak, confirming the phosphorylation of regenerated solution. Differential scanning calorimetry (DSC) showed that phosphorylation altered the intra- and inter-molecular interactions. Further experiments demonstrated that phosphorylation can be used to tailor the hydrophylicity/hydrophobicity ratio and crystalinity of silk fibroin films. Release profiling of a model drug was highly dependent on silk modification level. Cytotoxicity assays showed that exposure to lixiviates of phosphorylated films only slightly affected cellular metabolism and proliferation, although direct contact denoted a strong correlation between phosphorylation level and cell proliferation. This new methodology for tuning silk biomaterials to obtain specific structural and biochemical features can be adapted for a wide range of applications. Phosphorylation of silk fibroins may be applied to improve the cytocompatibility of any silk-based device that is considered to be in contact with live animal or human tissues.
    Full-text · Article · Oct 2014 · Biotechnology Journal
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