Stabilization of vaccines and antibiotics in silk and eliminating the cold chain

Tufts University, Department of Biomedical Engineering, Medford, MA 02155, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 07/2012; 109(30):11981-6. DOI: 10.1073/pnas.1206210109
Source: PubMed


Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent "cold chain" to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self-standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 °C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world.

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    • "Silk proteins are a particularly promising biomaterial due to the unique combination of biocompatibility, biodegradability, self-assembly, mechanical stability and control over structure and morphology [19] [20]. Silk-based biomaterials have been shown to safeguard the activity of sensitive biomolecules in harsh environments, allowing delivering molecules that otherwise quickly lose efficacy [21] [22] [23]. While SF as a bulk biomaterial already has interesting properties, the controlled assembly of ultrathin SF films is particularly interesting as it allows further control of the architecture of the drug delivery system and associated properties such as drug release [24] [25]. "
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    ABSTRACT: Herein, we describe the delivery of plasmid DNA (pDNA) using silk fibroin (SF) layer-by-layer assembled microcapsules. Deposition of fluorescently labeled SF onto polystyrene (PS) template particles resulted in increasing fluorescence intensity and decreasing surface charge in correlation to SF layer number. After removal of the PS core, hollow, monodisperse, and structurally stable SF microcapsules of variable size and shell thickness were obtained. Plasmid DNA encoding for enhanced green fluorescent protein (eGFP) was loaded onto 1 or 4 μm capsules, either by incorporation of pDNA within the innermost layer of the shell or by adsorption to the microcapsules surface, and in vitro pDNA release, cytotoxicty and eGFP expression were studied. Sustained pDNA release over 3 days was observed using both loading techniques, being accelerated in the presence of protease. DNA loaded SF microcapsules resulted in efficient cell transfection along with low cytotoxicity after 3 days incubation compared to treatment with pDNA/branched polyethylenimine complexes. Among the tested conditions highest transfection efficiencies were achieved using 1 μm capsules where pDNA was adsorbed to the capsule surface. Our results suggest that SF microcapsules are suitable for the localized delivery of pDNA, combining low cytotoxicity and high transfection efficiency.
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    • "Recent research from this group has reviewed the strategies to produce spider silk by recombinant DNA [75]. In addition, they have looked at silk-heparin biomaterials for vascular tissue engineering [69], silk hydrogels for treating breast cancer [70], antibiotic-releasing silk biomaterials for infections [71], electrical stimulation of silk films for enhancement of neural growth and silk containing dressings for increased wound healing [72], and silk protein matrices which thermostabilize labile vaccines and antibiotics [73]. The latter development is very exciting and could potentially solve the problem of transporting vaccines to remote parts of Africa when vaccines against malaria are finally produced (Table 3). "
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