Study Of Preparation And Drug Loading Property Of Schiff’s Base Modified Chitosan Derivatives

Chitosan is non-toxic, biocompatible and biodegradable. It is widely used inmany fields including controlled drug delivery system, antibacterial materials, thegene vector and etc. Chitosan derivatives are applied to drug carrier in the form ofgel, particle and nano micelle. Although drug availability can be improved in a way,its size cannot be controlled easily. The sizes of polymeric nano-micelles can becontrolled by changing the ratio of hydrophilic/hydrophobic groups and the averagemolecular weight of polymer. Imine (Schiff’s base) is a kind of dynamic covalentbond. It can be used as pH-sensitive site in pH-sensitive drug carrier. A new kind ofamphipathic chitosan derivative containing Schiff’s base was synthesized to formpH-sensitive self-assembled polymeric micelles, and used as hydrophobic drug carrierto improve bioavaibility in this paper.N-(4-alkoxy) benzaldehyde chitosan Schiff’s base(CS-DBA) was synthesizedthrough the Schiff’s base reaction between4-alkoxy benzaldehyde (DBA) andchitosan. Then2,3-glycidyl trimethylammonium chloride was introduced to CS-DBAto get goal product O-quaternary-N-(4-alkoxy) benzaldehyde chitosan Schiff’sbase(QA-CS-DBA). In order to improve drug loading capacity and encapsulationefficiency, β-cyclodextrin which could encapsulate hydrophobic drug well wasintroduced to CS-DBA while2-chloroethylamine was used as linker. Methyl iodidewas used to make amido quaterization to gain goal product N-(4-alkoxy)benzaldehyde chitosan Schiff’s base immobilize β-cyclodextrin(QC-CS-DBA) Inorder to investigate the relationship between structure and performance, chitosan withthe average molecular weight is50kDa and100kDa were used to modified and thecarbon chain length(8,10,12) were changed. The results of nuclear magneticresonance spectroscopy (1H NMR), fourier transform infrared (FTIR), elementalanalysis (EA) together indicated that these novel chitosan derivatives were succeedsynthesized.Both of QA-CS-DBA and QC-CS-DBA could self-assemble into micelles inaqueous solution. The micelles were spherical confirmed by SEM. Size of the micelles were uniformity measured by the particle size analyzer. The size ofQA-CS-DBA was between270~390nm and the size of QC-CS-DBA is between370~455nm.Pyrene was used as a fluorescent probe to test the critical micelleconcentration (CMC). The CMC of QA-CS-DBA was0.526~0.081mg/mL and theCMC of QC-CS-DBA micelle is0.495~0.085mg/mL. The size and CMC of themicelles will be smaller with the increase of the carbon numbers of carbon chain,while the size will be bigger and the Zeta will be higher when the molecular weighincrease. The zeta potential values of QA-CS-DBA and QC-CS-DBA micelles wereabout30mV indicating that micelles were stable.Under the best feed ratio of products and durg, the QA-CS-DBA micelle couldcarry ketoprofen with the drug loading capacity28.09~40.78%and the encapsulationefficiency40.78~52.70%, while QC-CS-DBA micelle could carry ketoprofen withthe drug loading capacity40.27~45.44%and the encapsulation efficiency67.41~83.15%. Compared with QA-CS-DBA, the drug loading capacity and theencapsulation efficiency of QC-CS-DBA was higher. To characterize pH sensitivity,drug release curve of drug-loaded micelles was examined in simulate solution at pH6.50and7.40. The results showed that both of QA-CS-DBA drug-loaded micellesand QC-CS-DBA drug-loaded micelles released slowly in pH7.40and released fastlyin pH6.50. The Zeta value of micelles in pH6.50was lower than the zeta potentialvalue in pH7.40, indicating the change of stability of self-assemble micelles. Itmeaned the drug-loaded micelles had pH sensitivity.