Studying On Character Of Self-aggregated Nanoparticles Of Cholesterol-bearing Pullulan

Polysaccharides are highly stable, safe, non-toxic, hydrophilic, biodegradable, abundant resources in nature and low cost in their processing. Hydrophobically modified polysaccharides, also named hydrophobized poly-saccharides, are amphiphilic in nature due to their hydrophilic backbones and hydrophobic pendants. Due to above outstanding merits, modified polysaccharides have received more and more attention in the area of drug delivery systems. We use succinic acid and 1,6-hexyl diisocyanate synthesizing CHSP and CHDP by directly grafting proper cholesterol residues onto different molecular weight pullulan. This dissertation also studied the relationships between length of the link arm system, cholesterol-based degree of substitution, molecular weight of pullulan and properties of nanoparticles. The main content of this research are shown as follows.Various cholesterol-bearing pullulans (CHDP and CHSP) with different molecular weights of parent pullulan and degrees of substitution (DS) of cholesteryl moiety were synthesized and characterized by fourier transform infrared (FT-IR), proton nuclear magnetic resonance (1H NMR), and X-ray diffraction (XRD). he degree of substitution (DS) of cholesterol moiety determined by 1H NMR between 5.2 and 3.9 cholesterol groups per hundred glucose units. CHSP and CHDP self-aggregated nanoparticles were prepared by analyzed in aqueous media and by proton nuclear magnetic resonance (1H NMR), dynamic laser light-scattering (DLS), transmission electron microscopy (TEM) and the fluorescence probe technologies. Critical association concentration (CAC) was studied by fluorescence probe method. CHSP and CHDP self-aggregated nanoparticles had a roughly spherical shape, Diameter of CHSP particle is 45-205 nm and diameter of CHDP is between 40 nm and 105 nm. With the DS of cholesteryl moiety increased, the diameter of the nanoparticle increased, critical micelle concentration decreased. Molecular weight of pullulan has nothing to do with the size change. With the length of the link arm decreased, critical micelle concentration decreased, the diameter of the nanoparticle increased and the stability of the nanoparticle enhanced.Doxorubicin (DOX) and Mitoxantrone (MTO) were loaded into the CHSP and CHDP nanoparticles by dialysis method. DOX-loaded CHSP self-aggregated nanoparticles were almost spherical in shape and their size rang from 140.5 to 308.3 nm, loading capacity (LC) of the nanoparticles rang from 8.8 to 18.6%. DOX-loaded CHDP self-aggregated nanoparticles were almost spherical in shape and their size rang from 104 to 368.1 nm, loading capacity (LC) of the nanoparticles rang from 9.3 to 16.7%.. XRD powder patterns showed that crystal peaks of DOX disappeared when DOX was entrapped into CHSP and CHDP nanoparticles. Loading capacity (LC) of the MTO-loaded nanoparticles was higher than the DOX-loaded nanoparticles in the same feed ratio. Loading capacity (LC) of the nanoparticles decreased and the size of loaded-nanoparticles changed greatly with the link arm length increased in the same feed ratio, degree of substitution and molecular weight polysaccharides. The in vitro release of DOX and MTO-lodaed CHSP and CHDP nanparticles demonstrated that the release behavior of DOX and MTO exhibited a two-phase pattern characterized by a fast initial release, then a slower and continous release. More apparent slow release of DOX.The fast initial release decreased and the slow release pattern increased with the link arm length decreased.DOX and MTO release rate decreased with the pH increase of the release media.