Polyelectrolyte Complex Nanoparticles Based on Methoxy Poly(Ethylene Glycol)-B-Poly (ε-Caprolactone) Carboxylates and Chitosan for Delivery of Tolbutamide.

ABSTRACT

In this study, a novel chitosan (CS)-modified nanoparticles (NPs) were developed to orally deliver tolbutamide (TOL). Methoxy poly(ethylene glycol)- b-poly(ε-caprolactone) carboxylates (mPEG2000-b-PCL4000) was synthesized via an esterification reaction. CS-modified mPEG2000-b-PCL4000-COOH NPs (CS@NPs) were fabricated by injecting mPEG2000-b-PCL4000-COOH NPs suspension (1.0 mg/mL) into CS solution (1.0 mg/mL, pH 5.0). Fourier transform infrared spectroscopy (FTIR) spectra were used to confirm the obtaining of mPEG2000-b-PCL4000-COOH. Transmission electron microscope (TEM) was carried out to observe morphology of all NPs. Nano ZS90 Malvern ParticleSizer were used to monitor the size distribution of obtained NPs. Thermogravimetry analysis (TGA) was performed to investigate the thermostability of CS@NPs. In vitro TOL release profiles were carried out in pH 1.2 and 7.4 buffers. FTIR spectra confirmed the obtaining of mPEG2000-b-PCL4000-COOH. TGA curves indicated that the protection of CS shells improved the thermostability of mPEG2000-b-PCL4000-COOH NPs. Cell tests indicated the CS@NPs had no obvious cytotoxicity, and they were easily taken up by 293T cells. In vitro release profiles showed that 91.0 ± 1.9% of encapsulated TOL were released from TOL-CS@NPs in pH 7.4 buffer. Therefore, the positive potential of CS@NPs could increase their combining capacity with intestinal mucosal cells. Finally, these NPs would improve the bioavailability of hydrophobic drugs.