Abstract
Cholesterol-modified pullulan (CHSP) conjugate with succinyl linkages was synthesized and characterized by fourier transform infrared (FT-IR), proton nuclear magnetic resonance (1H NMR) and X-ray diffraction (XRD). The degree of substitution (DS) of cholesterol moiety determined by 1H NMR ranged from 3.87 to 5.70 cholesterol groups per hundred glucose units. CHSP self-aggregated nanoparticles were prepared by probe sonication in aqueous media and analyzed by dynamic laser light-scattering (DLS), zeta potential, transmission electron microscopy (TEM) and the fluorescence probe technologies. These novel nanoparticles were almost spherical in shape, and their size, ranging from 73.0 to 51.8 nm, could be controlled by DS. The zeta potentials of CHSP self-aggregated nanoparticles were near zero in aqueous media. The value of critical aggregation concentration (cac) was dependent on the DS of cholesterol moiety. Mitoxantrone (MTO), as a model anticancer drug, was loaded into the CHSP nanoparticles by dialysis method. MTO-loaded CHSP self-aggregated nanoparticles were almost spherical in shape and their size increased from 153.1 to 174.2 nm with the MTO-loading capacity increasing from 4.35% to 14.29%. The encapsulation efficiency (EE) of the process and loading capacity (LC) of the nanoparticles increased with increasing cholesterol DS. XRD powder patterns showed that crystal peaks of MTO disappeared when MTO was entrapped into CHSP nanoparticles. The release behavior of MTO from CHSP self-aggregated nanoparticles was studied in vitro. The results showed that the release behavior of MTO from CHSP nanoparticles exhibited a sustained release, and MTO release rate decreased with increasing the pH value of media.
Keywords: Pullulan, cholesterol-modified pullulan, cholesterol succinate, self-aggregated nanoparticle, mitoxantrone, drug delivery
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