posted on 2019-08-26, 14:35authored byYuan-Fu Ding, Tianlei Sun, Shengke Li, Qiaoxian Huang, Ludan Yue, Liangkui Zhu, Ruibing Wang
Orally administered colon-targeted
formulations of drugs are of
great importance in managing diseases in the colon. However, it is
often challenging to maintain the integrity of such formulations during
delivery, particularly in the gastric environment, which may lead
to premature drug release before reaching the targeted colon. Herein,
an oral colon-targeted drug delivery hydrogel (OCDDH) was developed
through cucurbit[8]uril (CB[8])-mediated noncovalent cross-linking
of phenylalanine (Phe)-modified Konjac glucomannan (KGM), in which
berberine (BBR), a natural anti-inflammatory product originating from
Chinese medicine, was loaded into the hydrogel matrix. With the strong
host–guest complexation mediated cross-linking and the inherent
reversibility of such interactions, KGM-Phe@CB[8] hydrogel exhibited
a readily tunable degree of cross-linking and an excellent self-healing
capability, and therefore the hydrogel retained ultrahigh stability
in the gastric environment, which is important for orally administered
formulations to target the colon. In the colon, KGM may get degraded
by colon-specific enzymes, β-mannanase or β-glucosidase,
resulting in burst release of the loaded cargoes on site. The structure
and specific payload release of the hydrogel, with and without BBR,
have been fully characterized in vitro, and the therapeutic effect
of BBR-loaded KGM-Phe@CB[8] hydrogel was evaluated against dextran
sulfate sodium (DSS) induced ulcerative colitis (UC) in a mouse model.
Very interestingly, the BBR-loaded KGM-Phe@CB[8] hydrogel exhibited
significantly improved therapeutic efficacy in treating colitis, without
causing any systemic toxicity, when compared with free BBR. This strategy
may pave a new way in the development of advanced supramolecular OCDDH.