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

Annalisa Dalmoro1, Alexander Y Sitenkov2, Sara Cascone3

  • 1Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, 84084 Fisciano, SA, Italy.

International Journal of Pharmaceutics
|December 31, 2016
PubMed
Summary

Researchers developed novel enteric shell-core alginate microcarriers for colon cancer drug 5-fluorouracil (5-FU). This method achieved 50% encapsulation efficiency, significantly improving upon existing techniques for oral drug delivery.

Keywords:
5-Fluorouracil5-Fluorouracil (PubChem CID: 3385)Calcium chloride (PubChem CID: 5284359)Eudragit(®) E100 (PubChem CID: 107676)Eudragit(®) RL100 (PubChem CID: 104804)Eudragit(®) RS100 (PubChem CID: 104931)Hydrophilic drugPluronic F127 (PubChem CID: 24751)Polyelectrolyte complexationShell-core microparticlesSodium alginate (PubChem CID: 5102882)Ultrasonic atomization

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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.