Rizg Waleed Y, Naveen N Raghavendra, Kurakula Mallesh, Safhi Awaji Y, Murshid Samar S, Mushtaq Rayan Y, Abualsunun Walaa A, Alharbi Majed, Bakhaidar Rana B, Almehmady Alshaimaa M, Salawi Ahmad, Al Fatease Adel, Hosny Khaled M
Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Center of Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
Pharmaceuticals (Basel). 2022 Apr 18;15(4):491. doi: 10.3390/ph15040491.
Successful drug delivery by mucoadhesive systems depends on the polymer type, which usually gets adherent on hydration. The intended polymers must sustain the association with biomembranes and preserve or accommodate the drug for an extended time. The majority of hydrophilic polymers tend to make weak interactions like noncovalent bonds, which hampers the positioning of dosage forms at the required target sites, leading to inefficient therapeutic outcomes. It is possible to overcome this by functionalizing the natural polymers with thiol moiety. Further, considering that S-protected thiomers can benefit by improving thiol stability at a broad range of pH and enhancing the residence period at the required target, 2-mercapto-nicotinic acid (MA) was utilized in this present study to shield the free thiol groups on thiolated okra (TO). S-protected TO (STO) was synthesized and characterized for various parameters. Glibenclamide-loaded microspheres were formulated using STO (G-STO-M), and the process was optimized. The optimized formulation has shown complete and controlled release of the loaded drug at the end of the dissolution study. Cell viability assay indicated that the thiolated S-protected polymers gelated very well, and the formulated microspheres were safe. Further, G-STO-M showed considerable in vivo mucoadhesion strength. The glucose tolerance test confirmed the efficacy of STO formulation in minimizing the plasma glucose level. These results favor S-protection as an encouraging tool for improving the absorption of poorly aqueous soluble drugs like glibenclamide.
通过粘膜粘附系统成功给药取决于聚合物类型，该聚合物通常在水化时会发生粘附。预期的聚合物必须与生物膜保持结合，并长时间保留或容纳药物。大多数亲水性聚合物倾向于形成如非共价键这样的弱相互作用，这会妨碍剂型在所需靶位点的定位，导致治疗效果不佳。通过用硫醇部分对天然聚合物进行功能化可以克服这一问题。此外，考虑到S-保护的硫醇聚合物可以通过在广泛的pH范围内提高硫醇稳定性以及延长在所需靶标的停留时间而受益，本研究中使用2-巯基烟酸（MA）来保护硫醇化秋葵（TO）上的游离硫醇基团。合成了S-保护的TO（STO）并对其各种参数进行了表征。使用STO制备了载有格列本脲的微球（G-STO-M），并对该过程进行了优化。在溶出度研究结束时，优化后的制剂显示出所载药物的完全和可控释放。细胞活力测定表明硫醇化的S-保护聚合物凝胶化良好，且制备的微球是安全的。此外，G-STO-M显示出相当大的体内粘膜粘附强度。葡萄糖耐量试验证实了STO制剂在降低血浆葡萄糖水平方面的功效。这些结果支持S-保护作为改善格列本脲等难溶性药物吸收的一种有前景的工具。
