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Study On The Relationship Between Molecular Structure Of Galactosylated Fatty Acyl Chitosans And Their Micelle Characteristics

Posted on:2013-05-19Degree:MasterType:Thesis
Country:ChinaCandidate:C Q ShiFull Text:PDF
GTID:2254330422454672Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
For the unique core-shell structure and properties, polymeric micelles havepotential application in nano drug delivery system. However, the difference inmolecular structure of the carrier materials leads to different micelle characteristic,and consequently affects the role played by encapsulated drug. Therefore,investigation of the relationship between molecular structure of micelle materials andmicelle characteristic is necessary.In this study, a series of galactosylated fatty acyl chitosan with different molecularweight, different fatty chain length and degree of substitution (DS) were synthesizedas novel polymeric micellar materials for hepatocyte-targeting. Firstly, usingmethanesulfonic acid as reaction medium, fatty acyl chitosans (F-CS) weresynthesized by the reaction between chitosan and hydroxyl groups of fatty acylchloride (palmitoyl chloride and lauroyl chloride). Galactosylated fatty acyl chitosans(GF-CS) were synthesized by reactions of lactobionic acid and2-amino group ofF-CS under the activation of1-ethyl-3-(3-dimethyllaminopropyl) carbodiimidehydrochloride (EDC HCl). The structures of GF-CTS were characterized with Fouriertransform infrared (FTIR),1H nuclear magnetic resonance (1H-NMR) and elementalanalysis, and DS of fatty acyl and galactosylated groups were calculated. Thesolubility and critical micellar concentration (CMC) of F-CS and GF-CS weredetermined, and the particle size of polymeric micelles formed was measured. Therelationship between molecular structure of micelle materials and micelle characteristic was summarized.The reaction condition of preparing F-CS and GF-CS was investigated. Palmitoylchitosans (P-CS) with different molecular weight of chitosan were synthesized byreaction of chitosans and chloride at20℃for1hour. Lauroyl chitosans (L-CS) wereacquired at the following conditions:15℃,1hour for150000molecular weight ofchitosan;18℃,1hour for30000molecular weight of chitosan;20℃,1hour for5000molecular weight of chitosan. Then GF-CS was synthesized by reaction of lactobionicacid and F-CS at30℃for24hours. With solubility property in some organic solvents(chloroform, dimethyl sulfoxide) as index, the appropriate molar ratio of palmitoylchloride (or lauroyl chloride) to chitosan was investigated. The results were as follows:3:1~4:1and17:1~18:1for palmitoylation of150000molecular weight chitosan,3:1~7:1for lauroylation of150000molecular weight chitosan;2:1~6:1forpalmitoylation of30000molecular weight chitosan,2:1~7:1for lauroylation of30000molecular weight chitosan;2:1~8:1for palmitoylation of5000molecularweight of chitosan,2:1~10:1for lauroylation of5000molecular weight chitosan.The results of FTIR,1H-NMR and element analysis confirmed that F-CS andGF-CS were successfully synthesized. The DS of fatty acyl groups ranged from0.13mol to2.97mol, while the galactosylated group ranged from0.031mol to2.4mol.The solubility properties of F-CS and GF-CS synthesized were good in chloroform ordimethyl sulfoxide. The CMC and particle size of F-CS and GF-CS were0.26×10-6mol/L~42.83×10-3mol/L and100.0nm~500.0nm, respectively.The properties (CMC, particle size) of polymeric micelles formed by GF-CSwere related with their molecular structure (molecule weight of chitosan, DS andlength of fatty acyl groups, DS of galactosylated group). The DS of fatty acyl groupsand micellar properties changed regularly with the aliphatic chain length and molarratio of chloride to chitosan. In the condition of same (or similar) molar ratio ofchloride to chitosan, the DS of fatty acyl groups decreased with the increase ofmolecular weight of chitosan. With the increase of chloride/chitosan ratio, the DS offatty acyl groups increased, but the CMC and micelles size decreased. With the samechloride/chitosan ratio, the micelles size of GF-CS was smaller than that of F-CS. For the F-CS, GF-CS with same fatty length and chloride/chitosan ratio, the CMCincrease with the decreasing of chitosan moleculr weight,and particle size ofpolymeric micelles formed decrease with the decreasing of chitosan moleculr weight.
Keywords/Search Tags:Chitosan, galactosylated, fatty acylation, polymeric micelles, molecule structure, micelle characteristics
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