Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

• Published in: Drug delivery Vol. 23; no. 1; pp. 174 - 184
• Main Authors: Dong, Kai, Dong, Yalin, You, Cuiyu, Xu, Wei, Huang, Xiaoyan, Yan, Yan, Zhang, Lu, Wang, Ke, Xing, Jianfeng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.01.2016
• Subjects: Animals; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacokinetics; Colon - drug effects; Dexamethasone; Dexamethasone - administration & dosage; Dexamethasone - pharmacokinetics; Drug Delivery Systems; drug-loading; Hydrogels; Hydrogen-Ion Concentration; in vitro drug release study; in vivo pharmacokinetic study; Lactic Acid; pH-sensitive; Polyethylene Glycols; Polyglycolic Acid; Polymers; Rats; Solubility; Solvents; pH-sensitive; Dexamethasone; drug-loading; in vivo pharmacokinetic study; in vitro drug release study
• ISSN: 1071-7544; 1521-0464
• DOI: 10.3109/10717544.2014.908329

Context: As a glucocorticoid drug, dexamethasone has good therapeutic effects for ulcerative colitis. pH-sensitive hydrogels could make conventional changes of volume in response with different pH values. Meanwhile, they could load drugs depending on its internal three-dimensional network structure. Objective: Appropriate methods were used to improve the drug-loading capacity of hydrogel and exploring the colon-targeting character of dexamethasone hydrogel. Materials and methods: Different solvents (ethanol and 1,2-propanediol) were employed to dissolve dexamethasone as well as hydrogel monomer materials (poly(ethylene glycol) methyl ether (MPEG)-poly(lactide acid)-acryloyl chloride macromonomer, itaconic acid (IA) and MPEG-methacrylate), then mixing them together to prepare hydrogel through the heat-initiated free radical polymerization method. Differential scanning calorimetry and X-ray diffraction methods were used to verify whether dexamethasone was loaded into hydrogels. In vitro drug release behavior and in vivo pharmacokinetic study were also investigated in detail. Results: Dexamethasone was successfully loaded into hydrogel, and its loading capacity was improved (5 mg/g). Both the in vitro release study and the in vivo pharmacokinetic study showed the good colon-targeting character of the pH-sensitive P(LE-IA-MEG) hydrogel (T max  = 1.0 h, C max  = 2.16 µg/ml of dexamethasone; T max  = 3.9 h, C max  = 0.43 µg/ml of dexamethasone hydrogel). Discussion: Dexamethasone could be targeted to the colon site by P(LE-IA-MEG) hydrogel, thereby improving its therapeutic effect and reduce its side effects. Conclusion: P(LE-IA-MEG) hydrogel might have great potential application in colon-targeted drug delivery systems.