Enhancing the efficiency of thiomers: Utilizing a highly mucoadhesive polymer as backbone for thiolation and preactivation
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- 作者：Felix Prü ; fert ; Sonja Bonengel ; Claudia Menzel ; Andreas Bernkop-Schnü ; rch ; andreas.bernkop@uibk.ac.at
- 关键词：Thiomer ; Preactivated thiomer ; Mucoadhesion ; Highly mucoadhesive polymeric backbone
- 刊名：European Journal of Pharmaceutical Sciences
- 出版年：2017
- 出版时间：1 January 2017
- 年：2017
- 卷：96
- 期：Complete
- 页码：309-315
- 全文大小：502 K
- 卷排序：96
文摘
The objective of this study was to develop a novel thiomer with enhanced mucoadhesive properties using a highly mucoadhesive polymeric backbone. Fixomer™ A-30 (poly(methacrylic acid-co-sodium acrylamidomethyl propane sulfonate)), exhibiting a mucoadhesive strength superior to that of all other polymers, was thiolated by conjugation with l-cysteine and furthermore preactivated with 2-mercaptonicotinic acid (MNA). The resulting derivatives Fix-SH and Fix-S-MNA exhibited coupling rates of 755 μmol thiol groups and 304 μmol MNA per gram polymer, respectively. The mucoadhesive profile was evaluated with three different methods: tensile studies, rotating cylinder and rheological synergism. In tensile studies, a total work of adhesion of above 500 μJ was determined for the unmodified polymer that increased to around 750 μJ after thiolation and around 1500 μJ after preactivation. The adhesion time of Fix-SH on the rotating cylinder was 3.7-fold and that of Fix-S-MNA 6.8-fold longer compared to the unmodified polymer. A rheological synergism was observed for the unmodified polymer as well as the derivatives with a non-significant difference for Fix-SH but a 5.44-fold improvement for Fix-S-MNA. Fix-S-MNA showed a significantly improved swelling behavior with a water-uptake up to the 30-fold of its initial weight over > 50 h whereas thiolation showed only slight improvements. Derivatization had no significant influence on cell viability. According to the results, Fix-S-MNA seems to be a suitable polymer for mucoadhesive drug delivery systems.