Preparation Of Amphiphilic Cellulose Nano-micelles Via Molecular Self-assembly And Their Application In Drug Carriers

Amphiphilic cellulose copolymers have a special polymer structure,which contains both of the hydrophilic and hydrophobic segments.Due to this,they can self-assemble into nano-micelles with a core-shell structure in aqueous solution.The micelles are ideal water-soluble carrier for hydrophobic functional molecules,and can be used in a wide range of high-value fiels,eg.,drug carrier,sensor and bioimager.In this paper,a series of amphiphilic cellulose copolymers,with various types of hydrophobic groups,various ratios of hydrophilic/hydrophobic,different molecular weights,were synthesized by introducing hydrophobic groups onto the water-soluble cellulose derivatives.The relationship between the chemical structures of amphiphilic cellulose copolymers and their self-assembly behavior was discussed with the aim of obtaining nano-sized micelles with good stability and small particle size.The applications of cellulose-based self-assembled nano-micelles in water-soluble carriers of hydrophobic anticancer drugs were also studid,which could provide an new idea for developing the new anticancer carriers and high-value utilization of cellulose.The main contents of this thesis were listed as the followings.1.A novel kind of cationic cellulose-based amphiphilic polymer(QC-g-PCL)was prepared by homogeneous ring-opening copolymerization between quaternized cellulose(QC)and ?-caprolactone(?-CL)in the green solvent of 1-butyl-3-methylimidazolium chloride(BmimCl)ionic liquids.The hydrophilic/hydrophobic ratios in QC-g-PCL copolymers were adjusted by changing quantuary ammonium content in QC and the amount of e-CL to QC.The chemical structures,physical properties and self-assembly behavior of copolymers were characterized by FT-IR,NMR,XRD,TGA,TEM,DLS and fluorescence spectroscopy.The results indicated that QC-g-PCL copolymers were able to self-assemble into spherical nano-micelles and the micelles aqueous solution was prepared by ultrasonic-assisted dissolving method.The core of micelle was composed by the hydrophobic PCL segment,while the outer shell was constituted by the hydrophilic QC segment.Their self-assembly behaviour was correlated with the contents of hydrophilic/hydrophobic groups.The lowest CMC value of QC-g-PCL copolymer was up to 89 ?g/mL and the smallest average particle size was up to 170 nm.Due to the presence of quaternary ammonium groups,the surface charge of micelles was positive.The hydrophobic paclitaxel(PTX)and evodiamine(EVO)were used as model drugs in order to investigate the drug loading ability of QC-g-PCL micelles.With the increasing of the amount of hydrophobic PCL in copolymers,the encapsulation efficiency of PTX or EVO in micelles was increased.The highest encapsulation efficiencies of PTX and EVO in nanomicelles were 71.3%and 47.7%,respectively.2.Quaternized cellulose grafted poly(p-dioxanone)copolymers(QC0.44-g-PPDO)were homogeneously prepared using the ROP between p-dioxanone(PDO)and QC0.44.The QC0.44 with a 0.44 degree of subsutitution of quantuary ammonium was used as the raw material,while 1,8-diazabicycloundeca-7-ene(DBU)or 4-dimethylaminoptridine(DMAP)was used as the catalyst.The contents of hydrophobic PPDO in QC0.44-g-PPDO copolymers were adjusted by changing the types of catalyst,the dosage of catalyst,the dosage of monomer.The results indicated that the micelles self-assembled from QC0.44-g-PPDO were spherical in shape.Their average hydrodynamic sizes decreased from 246 nm to 106 nm with increasing the molar degree of substitution(MS)values of PPDO from 0.98 to 2.31.Moreover,the lowest critical micelle concentration value(CMC)of QC0.44-g-PPDO copolymer was 64 ?g/mL.The encapsulation efficiencies of PTX and EVO in QC0.44-g-PPDO nanomicelles were 61.8%and 57.5%,respectively.3.A series of QC0.44-g-PLA copolymers were synthesized via ROP between L-lactide(LA)and QC0.44 with DMAP or DBU as catalyst.By adjusting the reaction conditions,eg.,the molar ratio of LA to QC,the type and amount of catalyst,the hydrophobic/hydrophilic group value of the graft copolymers was altered.The molar substitution degree of PLA in QC0.44-g-PLA copolymers ranged over 0.83 to 2.54.The copolymer could self-assemble into spherical nano-micelles in aqueous solution.The average particle sizes of micelles decreased with increasing the MS values of PLA in copolymers.With increasing the MS value from 2.01 to 2.18,the CMC values of copolymers were decreased from 272?g/mL to 215?g/mL.The encapsulation efficiency of PTX and EVO in nanomicelles were increased with increasing the MS values of PLA,which was high up to 69.7%and 66.4%,respectively.4.A series of long-carbon chain hydrophobic modified hydroxyethyl cellulose polymers(HMHEC)were successfully prepared by etherification between hydroxyl group of hydroxyethyl cellulose and alkyl halides.The hydrophobic alkyl chain length was controlled by using different types of alkyl halides.The results indicated that the micelles were spherical in shape,and their average hydrodynamic sizes decreased with increasing alkyl chain length.The encapsulation efficiency of PTX and EVO in HMHEC nanomicelles were high up to 79.5%and 96.3%,respectively.5.A series of H-ESO-HEC polymers were synthesized via etherification and hydrolysis reaction between hydrophobic segment epoxy soybean oil(ESO)and hydrophilic segment HEC.The self-assembly behaviour of H-ESO-HEC copolymers in aqueous solution was found to be affected by the molecular weight of hydrophilic segments and the amount of hydrophobic segments.The average hydrodynamic sizes were ranged over 221 nm to 97 nm.The results indicated that the encapsulation efficienciesof PTX and EVO in H-ESO-HEC micelles increased with the enhancement of length of hydrophobic alkyl chains and the molecular weight of the hydrophilic segment which was high up to 69.1%and 62.9%,respectively.