Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for...

Area of Science:

• Biomedical Engineering
• Materials Science
• Pharmacology

Background:

• Ulcerative colitis (UC) requires effective colon-targeted drug delivery due to localized inflammation.
• Current therapies for UC face limitations, including rectal administration inconvenience and oral drug systemic toxicity.
• Budesonide (BUD) is a corticosteroid used for UC, but its administration methods have drawbacks.

Purpose of the Study:

• To design and prepare colon-targeted solid lipid nanoparticles (SLNs) encapsulating budesonide (BUD) for oral administration in ulcerative colitis (UC) treatment.
• To develop a drug delivery system with tunable, colon-specific release profiles.
• To evaluate the anti-inflammatory efficacy of the developed SLNs in a preclinical colitis model.

Main Methods:

• Synthesized a negatively charged surfactant (NaCS-C12) to create cellulase-responsive polyelectrolyte complexes (PECs) on SLNs.
• Formed PEC layers using NaCS and chitosan, controlling BUD release by adjusting layer number.
• Characterized BUD-loaded SLNs (SLN-BUD-2L) for particle size, zeta potential, and drug release kinetics.
• Assessed anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model.

Main Results:

• Developed nanoscale SLNs with a negative zeta potential, exhibiting targeted release in response to high cellulase activity.
• Demonstrated that the number of PEC layers precisely controlled the release rate and colon-specific behavior of BUD.
• SLN-BUD-2L showed significant anti-inflammatory effects in the DSS-induced colitis mouse model.

Conclusions:

• The developed BUD-loaded SLNs (SLN-BUD-2L) represent a promising oral colon-targeted drug delivery system for ulcerative colitis.
• The PEC coating strategy allows for tunable, colon-specific drug release, overcoming limitations of current BUD formulations.
• These findings suggest potential for advanced SLN-based therapies in treating inflammatory bowel diseases like UC.