Kai Dong1, Yalin Dong2, Cuiyu You1, Wei Xu1, Xiaoyan Huang1, Yan Yan1, Lu Zhang1, Ke Wang1, Jianfeng Xing1. 1. a School of Pharmacy, Health Science Center , Xi'an Jiaotong University , Xi'an , Shaanxi , China and. 2. b Depertment of Pharmacy, The first Affiliated Hospital of Medical College , Xi'an Jiaotong University , Xi'an , Shaanxi , China.
Abstract
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.
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.
Entities:
Keywords:
Dexamethasone; drug-loading; in vitro drug release study; in vivo pharmacokinetic study; pH-sensitive