Jingwen Luo,Jiang Sun,Xiaoting Luo,Yinghui Wei,Hangsheng Zheng,Chaofeng Mu,Wenjie Yao
Objective: This article aims to design low molecular weight chitosan (LMWC)-based conjugates of Rhein (RH) by means of an amino acid linker (Alanine) for improved solubility and enhanced bioavailability.Significance: Rhein is a potential candidate for the therapy of kidney disease. However, the poor solubility, inadequate bioavailability, and lack of proper formulation restrict its clinical applicability. LMWC-drug conjugates offer the potential to improve the water-solubility of RH, increase its oral absorption, and thereby enhance its bioavailability.Methods: The conjugates were synthesized via a carbodiimide reaction and confirmed using UV-vis, FTIR, and 1H-NMR spectroscopy. The water-solubility and in vitro release properties were evaluated. Free RH and RH-LMWC conjugates were administered at an equivalent oral gavage dose of RH at 35 mg/kg for pharmacokinetic studies in Sprague Dawley rats.Results: The conjugates with RH content of 9.65% were successfully synthesized and featured a satisfactory water-solubility of 9.73 mg/mL, which exhibited a sustained release pattern over 72 h, and the enzymes present may promote the degradation of the conjugate to increase the release of Rhein. Oral administration of RH-LMWC conjugates to rats led to seven-folds and 3.1-folds increase in the T1/2 and AUC0–∞, respectively, as compared to RH suspension.Conclusion: The present work demonstrated that the RH-LMWC conjugates exhibited sustained release properties with outstanding oral bioavailability enhancements compared to administration of RH itself. Potentially, RH-LMWC conjugates may serve as a promising lead for developing a new platform for RH oral delivery.
Double network hydrogels (DN gels) are one of most extensively investigated high strength hydrogels. However, most of DN gels are concern to macromolecules , low-molecular-weight gelators (LMWG)-based supramolecular hydrogels are rarely reported to fabricate recoverable DN gels. Owing to the low mechanical properties, LMWG-based supramolecular hydrogels are hardly fabricated as conductive materials for human motion monitoring. Herein, we report a general strategy to fabricate strong, tough and conductive cholate-based supramolecular gels with double network (DN) structure (i.e. La-cholate/PAAm DN gels), consisting of La-cholate supramolecular gel as first network and covalent polyacrylamide gel (PAAm gel) as second network, in which La-cholate supramolecular gel was self-assembled by La 3+ ions and sodium cholate under sonication via the synergistic effect of hydrogen bonds , hydrophobic interactions and metal-coordination. At optimal condition, La-cholate/PAAm DN gel exhibited high tensile properties (fracture stress of 0.314 MPa, fracture strain of 29.85 mm/mm, elastic modulus of 90 kPa, and work of extension of 5.678 MJ/m 3 ) and high toughness (tearing energy of 1098 J/m 2 ), which are comparable to conventional chemical or hybrid DN gels. Meanwhile, La-cholate/PAAm DN gel also showed rapid self-recovery property (stiffness recovery of 84% and toughness recovery of 46% after resting for 3 min) at room temperature and λ-dependent luminescent property under UV-light. More importantly, cholate-based supramolecular gels with DN structure could be prepared with various metal ions and monomers . Interestingly, our cholate-based DN gels were ionically conductive, which could be used as strain sensor to finely detect the human motions. We hope our design principles, along with the simple method and cholate-based DN gels, can be generally applied to develop a new generation of strong and tough LMWG-based supramolecular hydrogels with various functionalities.
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