Abstract
Growth factors have great therapeutic potential for various disease therapy and tissue engineering applications. However, their clinical efficacy is hampered by low bioavailability, rapid degradation in vivo and non-specific biodistribution. Nanoparticle based delivery systems are being evaluated to overcome these limitations. Herein, we have developed a thermosensitive heparin nanosponge (Hep-NS) by a one step photopolymerization reaction between diacrylated pluronic and thiolated heparin molecules. The amount of heparin in Hep-NS was precisely controlled by varying the heparin amount in the reaction feed. Hep-NS with varying amounts of heparin showed similar size and shape properties, though surface charge decreased with an increase in the amount of heparin conjugation. The anticoagulant activity of the Hep-NS decreased by 65% compared to free heparin, however the Hep-NS retained their growth factor binding ability. Four different growth factors, bFGF, VEGF, BMP-2, and HGF were successfully encapsulated into Hep-NS. In vitro studies showed sustained release of all the growth factors for almost 60 days and the rate of release was directly dependent on the amount of heparin in Hep-NS. The released growth factors retained their bioactivity as assessed by a cell proliferation assay. This heparin nanosponge is therefore a promising nanocarrier for the loading and controlled release of growth factors.
Highlights
Advances in protein purification and recombinant DNA technology have made it possible to obtain many natural and recombinant growth factors for clinical applications
Biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres and nanoparticles functionalized with heparin were widely used for the delivery of several growth factors, such as basic fibroblast growth factor, and vascular endothelial growth factor (VEGF), amongst others[11,12,13]
The heparin nanosponges were characterized as a new type of carrier for loading and controlled release of four different yet important growth factors; basic fibroblast growth factor (bFGF), VEGF, bone morphogenic protein 2 (BMP-2), and hepatocyte growth factor (HGF)
Summary
Won Il Choi[1], Abhishek Sahu[2], Cristian Vilos 3,4, Nazila Kamaly 5, Seong-Min Jo6, Jin Hyung Lee1 & Giyoong Tae[2]. To attain a therapeutic effect in vivo, requires administration of extremely high doses, which often results in unwanted side effects such as hypotension, retinopathy, or progression of malignant tumors due to off-target effects at distant sites[1,5] To improve their clinical success and reduce any unwanted side effects there is a considerable need to optimize growth-factor delivery so that their local concentration in the target tissue is sustained over time, and their bioactivity is retained with minimal impact on normal organs[3,5]. Micro/nano-particles, hydrogels, and porous 3D scaffolds are a few examples of different systems used for growth factor delivery[3,5,6] Their release profiles are controlled by adjusting the physiochemical properties of the vehicle, such as porosity, degree of cross-linking and degradation rate. The bioactivity of the released growth factor was analyzed
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