Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy.
Department of Chemical, Material and Environmental Engineering, Sapienza University of Rome, Via Eudossiana 18, 00184 Rome, Italy.
Carbohydr Polym. 2017 Oct 15;174:960-969. doi: 10.1016/j.carbpol.2017.07.008. Epub 2017 Jul 6.
Physical hydrogels of a high-carboxymethylated derivative of scleroglucan (Scl-CM) were investigated as potential systems for topical drug delivery using three different therapeutic molecules (fluconazole, diclofenac and betamethasone). Rheological tests were carried out on drug-loaded hydrogels along with in-vitro release studies in a vertical Franz cell, in order to investigate if and how different drugs may influence the rheological and release properties of Scl-CM hydrogels. Experimental results and theoretical modeling highlighted that, in the absence of drug/polymer interactions (as for fluconazole and betamethasone) Scl-CM matrices offer negligible resistance to drug diffusion and a Fickian transport model can be adopted to estimate the effective diffusion coefficient in the swollen hydrogel. The presence of weak drug/hydrogel chemical bonds (as for diclofenac), confirmed by frequency sweep tests, slow down the drug release kinetics and a non-Fickian two-phase transport model has to be adopted. In-vivo experiments on rabbits evidenced optimal skin tolerability of Scl-CM hydrogels after topical application.
高羧甲基化支链淀粉(Scl-CM)衍生物的物理水凝胶被研究作为局部药物传递的潜在系统,使用三种不同的治疗分子(氟康唑、双氯芬酸和倍他米松)。对载药水凝胶进行了流变学测试,并在垂直 Franz 细胞中进行了体外释放研究,以研究不同药物是否以及如何影响 Scl-CM 水凝胶的流变学和释放特性。实验结果和理论模型表明,在不存在药物/聚合物相互作用的情况下(如氟康唑和倍他米松),Scl-CM 基质对药物扩散的阻力可以忽略不计,可以采用菲克扩散模型来估计溶胀水凝胶中的有效扩散系数。通过频率扫描测试证实了弱的药物/水凝胶化学相互作用的存在(如双氯芬酸),这会减缓药物释放动力学,必须采用非菲克扩散两相传输模型。兔体内实验证明,局部应用 Scl-CM 水凝胶具有良好的皮肤耐受性。