结冷胶
化学
黏膜黏附
自愈水凝胶
木瓜蛋白酶
羧甲基纤维素
药物输送
色谱法
毒品携带者
生物化学
高分子化学
有机化学
钠
酶
食品科学
作者
Caroline Santos Alves de Lima,M. Isabel Rial-Hermida,Lucas Freitas de Freitas,Ana F Pereira-da-Mota,María Vivero-Lopez,Aryel H. Ferreira,Sławomir Kadłubowski,Gustavo H.C. Varca,Ademar B. Lugão,Carmen Alvarez‐Lorenzo
标识
DOI:10.1016/j.ijbiomac.2023.124957
摘要
Local treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.
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