Anemoside B4 Rectal Thermosensitive In Situ Gel to Treat Ulcerative Colitis by Overcoming Oral Bioavailability...

Area of Science:

• Pharmacology and Drug Delivery
• Gastroenterology
• Materials Science

Background:

• Anemoside B4 (AB4), a saponin from Pulsatilla chinensis, has anti-inflammatory and anti-tumor properties.
• Clinical use of AB4 for ulcerative colitis (UC) is limited by poor absorption and low oral bioavailability.
• Rectal in situ gels (ISGs) offer a potential alternative delivery route.

Purpose of the Study:

• To engineer and optimize thermosensitive rectal ISGs for AB4 delivery.
• To enhance AB4's mucosal permeation, bioavailability, and therapeutic efficacy for UC using absorption enhancers.
• To evaluate the safety and effectiveness of the developed ISGs.

Main Methods:

• Screening of permeation enhancers (hydroxypropyl-β-cyclodextrin, sodium caprate) using Caco-2 cells and Franz diffusion cells.
• Optimization of poloxamer 407 (P407), poloxamer 188 (P188), and hydroxypropyl methyl cellulose (HPMC) concentrations using Box-Behnken design.
• Characterization of ISGs including in vitro release, pharmacokinetics, rectal tolerability, retention time, and in vivo UC model efficacy.

Main Results:

• Optimized ISGs (HP-β-CD-AB4-ISG and SC-AB4-ISG) were successfully formulated with specific enhancer and polymer concentrations.
• The ISGs exhibited suitable physicochemical properties (gelation temperature, pH, strength) and demonstrated prolonged rectal retention.
• Significant improvements in AB4 bioavailability and notable alleviation of UC symptoms were observed in vivo.

Conclusions:

• Poloxamer-based thermosensitive rectal ISGs with absorption enhancers provide an effective platform for targeted AB4 delivery to the colorectum.
• This approach overcomes oral administration limitations for AB4 in treating UC.
• The developed rectal ISGs warrant further clinical investigation for UC and other colorectal inflammatory diseases.