Preparation Of ?-glucan Based Micelle Aggregation By Cellulose With Low Polymerization Degree And Its Release Behavior As Anti-cancer Drug Carrier

Low solubility in water of anticancer drugs affects the continuous treatment effect to a large extent,so the dispersing carry and slow-release of anticancer drugs has become a research hotspot.This work proposed to degrade natural polysaccharides cellulose to water soluble ?-glucan(?-WSG)and water-insoluble ?-glucan(?-WIG)with biodegradability and biocompatibility,which were modified to amphiphilic ?-glucan based micelle aggregations as carriers of the regular anticancer drug docetaxel(DTX),and studied the drug release behavior of the drug carriers.Firstly,under the condition of 85% concentrated phosphoric acid medium,natural polysaccharides,cellulose(cotton)degrading to ?-WSG with the degree of polymerization(DP)of 7 and ?-WIG with the DP of 60~110 had been investigated.The molecular weight distribution of ?-WSG and ?-WIG had been determined in detail by GPC,and their structures had been characterized by infrared spectrumand X-ray diffraction analysis.Under the suitable conditions,the DP,the extraction yield and the purity of ?-WSG were 7,35.42% and 96.60%,respectively,and the lowest DP of ?-WIG was 66 with the extraction yield of 40.86%.The reaction activity of ?-glucan was markedly higher than that before degradation.Secondly,with n-heptane as dispersant,under the anhydrous stannic chloride as catalyst,?-WSG with the DP of 7 was developed for a series of amphiphilic water soluble ?-glucan-polypropylene oxide(?-WSG-PPO)surfactants by glycosylation between the terminal hydroxyls of glucan and propylene oxide,and addition reaction by ring-open reaction of propylene oxide.The structures and properties of series ?-WSG-PPO amphiphilic polymers were discussed.The critical micelle concentration(CMC)and the micellar aggregation numbers(N)of series of ?-WSG-PPO amphiphilic polymers decreased with the increase of polyoxypropylene chain,but the particle sizes increased(about 200 nm or so).?-WSG-PPO micelles forms were typical of the spherical.Thirdly,using ?-WIG with the DP of 66 derived from cellulose degradation as the the desired material,with n-heptane as dispersant,under the anhydrous stannic chloride as catalyst,the ?-WIG was developed for a series of amphiphilic water insoluble ?-glucan-polyethylene oxide(?-WIG-PEO)surfactants by glycosylation between the terminal hydroxyls of glucan and ethylene oxide,and addition reaction by ring-open reaction of ethylene oxide.The structures and properties of series of ?-WIG-PEO amphiphilic polymers were discussed.The CMC and the particle sizes of series of ?-WIG-PEO amphiphilic polymers increased with the increase of polyoxyethylene chain.?-WIG-PEO micelle forms were typical of the spherical.Fourthly,using the epoxy propane as the linkers,it built ?-WSG-PPO-DTX drug transport systems through the chemical coupling between the ?-WSG-PPO amphiphilic polymer and anti-cancer drug docetaxel(DTX).It also contructed carriers of physical load DTX using ?-WIG-PEO micelle aggregations prepared by emulsion solvent evaporation method.By comparing the structure and properties of two kinds of carriers found that ?-WSG-PPO-DTX had a maximum drug loading rate of 40.30 % for DTX,and the maximum drug loading rate on physically loading DTX using ?-WIG-PEO micelle was 26.68 %.The micelle forms of two kinds of ?-glucan-based micelle aggregation loaded DTX were typical of the spherical,and showed obvious core-shell structure.Finally,the drug release behavior in animal vivo and in simulated biological buffer solution(PBS)vitro of ?-glucan-based micelle aggregation loaded DTX had been studied,thereby established simulated biological buffer solution vitro release dynamic model and vivo pharmacokinetic equation and discussed the drug control release mechanism.The results indicated that the drug release behavior of ?-glucan-based micelle aggregation in simulated biological buffer solution vivo fitted to first order kinetic model,and the release of the DTX controlled by relaxation and diffusion of amphiphilic polymer chain segment.The release behavior of ?-WSG-PPO-DTX in animal vivo reflected a long-circulating characteristic,which created the conditions for drug targeting to reach disease.In conclusion,the degradation of cellulose derivatives ?-glucan-based micelle aggregation as a carrier of anti-cancer drug DTX has a good dispersing carry and slow-release effect.The reaearch results in this paper not only broaden the application scope in the field of pharmaceutical engineering,but also expand the application value of fiber,and give a new academic significance to the scientific principle of the macromolecular miceller aggregation and the colloid interface chemistry in the solution.