Augmentation of Antidiabetic Activity of Glibenclamide Microspheres Using S-Protected Okra Powered by QbD: Scintigraphy and In Vivo Studies

• Published in: Pharmaceuticals (Basel, Switzerland) Switzerland), 2022-04, Vol.15 (4), p.491
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Acids; Bioavailability; central composite design; Chemical bonds; Drug delivery systems; Drug dosages; glibenclamide; Hydration; microsphere; mucoadhesion; Polymers; sustainability of natural resources; thiolation; Viscoelasticity; Viscosity
• ISSN: 1424-8247; 1424-8247
• 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.