Baicalin (BG) is a natural glycoside with several promising therapeutic and preventive applications. However, its pharmaceutical potential is compromised by its poor water solubility, complex oral absorption kinetics, and low bioavailability. In this work, BG was incorporated in a series of chitosan (Ch)/glycerophosphate (GP)-based thermosensitive hydrogel formulations to improve its water solubility and control its release profile. Molecular interactions between BG and GP were investigated using Fourier transform infrared spectroscopy (FT-IR), and the ability of GP to enhance the water solubility of BG was studied in different release media. Drug-loaded Ch/GP hydrogels were prepared and characterized for their gelation time, swelling ratio, and rheological properties in addition to surface and internal microstructure. Polyethylene glycol (PEG) 6000 and hydroxypropyl methyl cellulose (HPMC) were incorporated in the formulations at different ratios to study their effect on modulating the sol–gel behavior and the in vitro drug release. In vivo pharmacokinetic (PK) studies were carried out using a rabbit model to study the ability of drug-loaded Ch/GP thermosensitive hydrogels to control the absorption rate and improve the bioavailability of BG. Results showed that the solubility of BG was enhanced in the presence of GP, while the incorporation of PEG and/or HPMC had an impact on gelation time, rheological behavior, and rate of drug release in vitro. PK results obtained following buccal application of drug-loaded Ch/GP thermosensitive hydrogels to rabbits showed that the rate of BG absorption was controlled and the in vivo bioavailability was increased by 330% relative to BG aqueous oral suspension. The proposed Ch/GP thermosensitive hydrogel is an easily modifiable delivery platform that is not only capable of improving the solubility and bioavailability of BG following buccal administration but also can be suited for various local and injectable therapeutic applications.

中文翻译：

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黄ical素用于多种生物医学应用的热凝胶平台

黄ical苷（BG）是一种天然糖苷，具有多种有希望的治疗和预防应用。但是，由于其水溶性差，口服吸收动力学复杂和生物利用度低，其药理潜力受到了损害。在这项工作中，将BG掺入了一系列基于壳聚糖（Ch）/甘油磷酸酯（GP）的热敏水凝胶配方中，以改善其水溶性并控制其释放特性。使用傅里叶变换红外光谱（FT-IR）研究了BG与GP之间的分子相互作用，并研究了GP在不同释放介质中增强BG水溶性的能力。制备了载有药物的Ch / GP水凝胶，并对其凝胶化时间，溶胀率和流变性质以及表面和内部微观结构进行了表征。以不同比例将聚乙二醇（PEG）6000和羟丙基甲基纤维素（HPMC）掺入制剂中，以研究它们对调节溶胶-凝胶行为和体外药物释放的影响。使用兔子模型进行了体内药代动力学（PK）研究，以研究载药的Ch / GP热敏水凝胶控制BG的吸收速率并提高其生物利用度的能力。结果表明，在GP存在下BG的溶解度增加，而PEG和/或HPMC的掺入对胶凝时间，流变行为和体外药物释放速率有影响。将载药的Ch / GP热敏水凝胶颊涂于兔后获得的PK结果表明，相对于BG水性口服混悬液，BG吸收速率得到控制，体内生物利用度提高了330％。拟议的Ch / GP热敏水凝胶是一个易于修改的输送平台，不仅能够在颊部给药后改善BG的溶解度和生物利用度，而且还适用于各种局部和可注射的治疗应用。