Colon-Targeted Mucoadhesive PLGA Microspheres Loaded with Ramulus Mori Alkaloids for Enhanced Water-Soluble Drug...

Area of Science:

• Pharmacology and Drug Delivery
• Gastroenterology
• Materials Science

Background:

• Ulcerative colitis (UC) is a chronic inflammatory disease with limited treatment options and significant impact on quality of life.
• Ramulus Mori alkaloids (SZ-A) show therapeutic potential for UC due to anti-inflammatory and barrier repair properties.
• Oral administration of SZ-A causes gastrointestinal side effects (flatulence) due to alpha-glucosidase inhibition in the small intestine, necessitating targeted delivery.

Purpose of the Study:

• To develop a colon-targeted formulation of SZ-A to improve UC therapy and mitigate side effects.
• To enhance the therapeutic efficacy of SZ-A by ensuring its delivery to the inflamed colonic region.

Main Methods:

• Preparation of sodium alginate-modified PLGA microspheres encapsulating SZ-A (SZ-A@MSs) using thiolated hyaluronic acid as an intermediate carrier.
• Utilized a double emulsion method for efficient SZ-A encapsulation.
• Characterization of microsphere properties including particle size, drug loading, and encapsulation efficiency.

Main Results:

• SZ-A@MSs exhibited a particle size of ~30 µm, drug loading of ~12.0%, and encapsulation efficiency of ~31.7%.
• In vitro studies demonstrated antioxidant and anti-inflammatory effects of SZ-A@MSs in Raw264.7 cells.
• In vivo imaging confirmed good colon retention and sustained-release properties of SZ-A@MSs.
• Pharmacodynamic studies showed SZ-A@MSs effectively inhibited weight loss, colonic atrophy, and inflammatory factor secretion in a UC model.

Conclusions:

• The developed SZ-A@MSs possess excellent colon-targeting capabilities.
• This formulation enhances therapeutic effects for ulcerative colitis by enabling targeted delivery and sustained release.
• SZ-A@MSs represent a promising strategy for improved ulcerative colitis treatment, minimizing systemic side effects.