Pacelli Settimio, Paolicelli Patrizia, Dreesen Inge, Kobayashi Shuichiro, Vitalone Annabella, Casadei Maria Antonietta
Department of Drug Chemistry and Technologies, Sapienza University of Rome, Ple Aldo Moro 5, 00185 Rome, Italy.
Department of Drug Chemistry and Technologies, Sapienza University of Rome, Ple Aldo Moro 5, 00185 Rome, Italy.
Int J Biol Macromol. 2015 Jan;72:1335-42. doi: 10.1016/j.ijbiomac.2014.10.046. Epub 2014 Oct 27.
In this work, a natural polysaccharide gellan gum (GG) has been modified with methacrylic groups (GG-MA) and combined with polyethylene glycol dimethacrylate (PEG-DMA) in order to create novel injectable hydrogels that can be easily delivered through a needle and photocross-linked in the injection site. A novel synthetic procedure for methacrylation of GG has been proposed to better control its derivatization. Different degrees of functionalization have been achieved and their effects on the solubility and mechanical properties of GG-MA were investigated. A good balance in terms of hydrophilicity and elasticity of the corresponding hydrogels was identified, although not suitable enough as injectable material for the treatment of damaged soft tissues. For this reason, several concentrations and different molecular weights of PEG-DMA were investigated to modulate the composition of GG-MA hydrogels and overcome their extreme fragility. Swelling abilities of the hydrogels in different media were studied as a key parameter able to affect the release profile of loaded therapeutic agents. Model molecules having different spherical hindrance (sulindac and vitamin B12) were then chosen to study how the hydrogels were able to modulate their diffusion profiles over time. Finally, the hydrogel's safety was evaluated trough an MTT cytotoxicity test on human fibroblasts.
在这项工作中，天然多糖结冷胶（GG）已用甲基丙烯酸基团进行改性（GG-MA），并与聚乙二醇二甲基丙烯酸酯（PEG-DMA）结合，以制备新型可注射水凝胶，这种水凝胶能够轻松通过针头注射，并在注射部位进行光交联。已提出一种用于GG甲基丙烯酸化的新型合成方法，以更好地控制其衍生化。实现了不同程度的功能化，并研究了其对GG-MA的溶解性和机械性能的影响。确定了相应水凝胶在亲水性和弹性方面的良好平衡，尽管作为治疗受损软组织的可注射材料还不够合适。因此，研究了几种浓度和不同分子量的PEG-DMA，以调节GG-MA水凝胶的组成并克服其极度脆弱性。研究了水凝胶在不同介质中的溶胀能力，这是一个能够影响负载治疗剂释放曲线的关键参数。然后选择具有不同球形位阻的模型分子（舒林酸和维生素B12）来研究水凝胶如何随时间调节其扩散曲线。最后，通过对人成纤维细胞的MTT细胞毒性试验评估了水凝胶的安全性。
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