Study On Preparation Of Photocrosslinked Poly(Ether-anhydride) Gel Nanoparticles And The Entrapment Of Hydrophobic Drugs

Biodegradable poly(ether-anhydride) gel nanoparticles (GNP) with hydrophobic crosslinked core-hyphophilic shell sturcture were prepared, which could overcome the instable problems of polymer micelles, such as disintegration by dilution in the body, and could be used to solubilize hydrophobic drugs. The structure and hydrophilicity/hydrophobicity of GNP was modified by changing PEG chain length and adding hydrophobic monomers, which could finally affect the degradability and the drug loading capacity GNP.Amphiphilic photocrosslinkable ether-anhydride macromers and two hydrophobic photocrosslinkable monomers were synthesized initially and characterized by FT-IR and 1H NMR spectrum, then poly(ether-anhydride) gel nanoparticles were prepared by emulsion photopolymerization method, which were found to be spherical or elliptoid in shape and with obvious core-shell structure when stearic monoacrylic anhydride (MSA) was added. The particle size measured by laser particle analyzer (LPA) was 340-670 nm. The X-ray diffraction of GNP showed that the crystality of PEG chain decreased and MSA was grafted to core networks in amorphous state. GNP could degrade in a few hours in vitro, and the degradation rate could be tailored by regulating the length of PEG chain.Indomethacin (IND) was chosed to be the model hydrophobic drugs, which was entrapped in the hydrophobic crosslinked core by in situ or post embedding method. The FT-IR of IND in situ loaded GNP showed that there was no chemical change of IND structure during the preparation indicating that IND kept stable during the entrapment. The particle size of IND loaded GNP measured by LPA became slightly larger than that of blank GNP. The X-ray diffraction showed that IND was highly dispersed in the hydrophobic crosslinked core and stayed in amorphous or molecular state when in situ loaded in GNP, while some of the loaded IND stayed in crystal state when it was post embedded in GNP. The drug loading and encapsulation efficacy of IND by in situ method was affected by many factors, such as the different ether-anhydride macromers and the hydrophobicity of the core, which could be as high as 65% in this thesis. The in vitro release behavior of IND loaded GNP showed that GNP prepared by ether-anhydride macromers could improve the dissolution rate greatly, especially the GNP prepared by larger weight macromers. But the dissolution rate decreased obviously and IND could not be released completely after MSA added. The dissolution results implied that drug dissolution rate is closely related to the hydrophilic shell thickness and crosslinking density and hydrophobicity of the core. Six drugs loaded GNP could solubilize IND in different levels by measuring dissolution in water.The results indicate that these novel poly(ether-anhydride) gel nanoparticles with hydrophobic crosslinked core-hyphophilic shell are potential in solubilizing and deliverying hydrophobic drugs.