(584y) A Novel PEC Drug Carrier of Nacs-CS-PPS Microcapsules for Colon-Specific Drug Delivery

Polyelectrolyte complexes (PEC) prepared with sodium cellulose sulfate (NaCS), chitosan (CS)/water soluble chitosan (WSC) and sodium polyphosphate (PPS) were developed with a simple preparation process, which can be used as a novel colon-specific drug delivery system. NaCS is a polyanion with –SO₃^- groups while CS/WSC is a polycation with –NH₃⁺groups, and PPS was used as a cross-linking agent. Based on the PEC formed via ionization reaction, spherical microcapsules loaded with drugs were prepared by an orifice-polymerization method. This system was used to successfully load two model drugs: a small molecular drug and a protein drug.

The NaCS-CS-PPS microcapsules loaded with 5-aminosalicylic acid (5-ASA) as a model small molecular drug were prepared. The microcapsules prepared had an average diameter of 1.90 mm with loading efficiency (LE%) of 60.77% and encapsulation efficiency (EE%) of 90.03%. Scanning electron microscope (SEM) results showed that the microcapsules had a double-walled capsule structure with an outer wall thickness of approximately 4.40 µm and inner wall (shell) thickness of approximately 187.14 µm. SEM transection images of the microcapsules showed that 5-ASA entrapped in the microcapsule was in a crystal form. The results of in vitroswelling/erosion and release analysis showed that the drug was preferentially and completely released in simulated colonic fluid (SCF, pH 6.4) under the mechanism of anomalous transport.

The NaCS-CS/WSC-PPS microcapsules loaded with lactoferrin (LF) as a model protein drug were also prepared. The average diameter of NaCS-CS-PPS microcapsules and NaCS-WSC-PPS microcapsules were 1.85 and 1.97 mm, and the coefficient of variation (CV) value were 5.11% and 4.99%, respectively. SEM studies showed that both of the microcapsules had a typical wall-capsule structure with smooth surfaces. 1H-NMR spectrum confirmed that the WSC used was in the form of chitosan hydrochloride. Fourier transform infrared spectroscopy (FTIR) spectra analysis indicated that –NH₃⁺ of CS/WSC, –SO₃^- of NaCS and –[P₂O₅^4-]– of PPS may react and form PEC. Thermo-gravimetric analysis (TGA) studies showed that the weight loss of the NaCS-CS-PPS microcapsules was higher than that of the NaCS-WSC-PPS microcapsules in the same temperature, which indicated that the later one had better thermal stability. Drug loading and encapsulation efficiency studies showed that NaCS-CS-PPS microcapsules had LE% of 49.06% and EE% of 86.3%, respectively, which was higher than that of NaCS-CS-PPS microcapsules of 45.60% and70.72%. In vitrorelease studies showed that both of the microcapsules had a regular drug release behaviors with a trend of slow increasing, and the drug was released sustainably and completely in SCF (pH 5.5-7.0).

All of these results indicated that the microcapsules based on the PEC prepared with NaCS, CS/WSC and PPS can be a good candidate as an enzyme-triggered controlled release drug carrier for colon-specific drug delivery systems.

Acknowledgments: This work was supported by the National Natural Science Foundation of China and the Doctoral Programs Foundation of Ministry of Education of China.