In vitro and in vivo study of pH-sensitive and colon-targeting P(LE-IA-MEG) hydrogel microspheres used for ulcerative colitis therapy

摘要

Graphical abstract Display Omitted Highlights ? P(LE-IA-MEG) hydrogel microspheres (HMSs) were synthesized as the carrier of hydrocortisone sodium succinate (HSS) for ulcerative colitis therapy. ? The swelling and in vitro release studies indicated its good pH sensitivity. ? The pharmacokinetic study and the drug residues in the gastrointestinal tract study demonstrated its desirable colon targeting property. ? The therapeutic effects study revealed its ameliorative effects on the colitis mice. Abstract Hydrocortisone sodium succinate (HSS) is an anti-inflammatory drug, but its application on ulcerative colitis (UC) treatment is limited by its associated side-effects. To solve this problem, a kind of pH-sensitive P(LE-IA-MEG) hydrogel microspheres (HMSs) were prepared as the drug carrier of hydrocortisone sodium succinate (HSS) for the treatment of UC. The P(LE-IA-MEG) HMSs were spherical in shape with good dispersion and the mean particle size was 34.87±0.90μm. HSS was successfully loaded into the P(LE-IA-MEG) HMSs. The in vitro release study of HSS-loaded HMSs (HSS-HMSs) revealed that the HSS-HMSs possessed desirable pH-sensitivity, the cumulative release rate was 4.07% and 94.64% in the solution with pH 1.2 and pH 7.4 solution during 12h, respectively. Furthermore, the study on pharmacokinetic, gastrointestinal drug residue and side-effects were conducted to evaluate the in vivo colon-targeting property of the HSS-HMSs. All the results showed that the HSS-HMSs could deliver HSS to the colon as well as reduce its premature absorption in the upper gastrointestinal tract. Finally, the HSS-HMSs showed better ameliorative effects and therapeutic effects on mice with experimental colitis as compared to HSS. In conclusion, the HSS-HMSs had great potential in the treatment of UC.