Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Drug Delivery Systems

Background:

• Developing efficient drug delivery systems for hydrophilic chemotherapeutics like 5-fluorouracil (5-FU) is crucial for colon cancer treatment.
• Existing methods for encapsulating 5-FU often result in low efficiencies and lack gastroresistance for oral administration.
• Alginate-based microcarriers offer potential for controlled drug release but require functionalization for targeted delivery.

Purpose of the Study:

• To develop an efficient protocol for encapsulating 5-fluorouracil (5-FU) into enteric shell-core alginate microcarriers.
• To enhance the gastroresistance and controlled release properties of the microcarriers for potential oral colon cancer therapy.
• To achieve significantly higher encapsulation efficiencies compared to existing methods.

Main Methods:

• Utilized ultrasonic atomization combined with polyelectrolyte complexation to create shell-core alginate microcarriers.
• Employed a two-stage complexation process: first with CaCl2/dichloromethane emulsion, then with Eudragit® RS 100 in dichloromethane for enteric coating.
• Characterized microcarriers using FTIR and DSC to confirm interpolyelectrolyte complex formation, drug stability, and amorphous dispersion.

Main Results:

• Achieved a high 5-fluorouracil (5-FU) encapsulation efficiency of approximately 50%, a substantial improvement over the reported 10% in literature.
• Developed microcarriers exhibited good gastroresistance, with less than 35% cumulative 5-FU release at pH 1 (simulating gastric conditions).
• Successfully formulated enteric-coated microcarriers into tablets for potential oral administration, demonstrating slower 5-FU release.

Conclusions:

• The developed ultrasonic atomization and polyelectrolyte complexation protocol efficiently encapsulates 5-fluorouracil in enteric alginate microcarriers.
• The shell-core enteric-coated microcarriers show promising gastroresistance and controlled release characteristics for oral colon cancer drug delivery.
• The microcarrier tablets represent a viable dosage system for enhanced oral administration of 5-FU.