Lipase-catalyzed Cellulose Esters In Mixed ILs And Its Application In Drug Delivery

Biomass materials have been recognized due to their advantages with the environmental pollution of petrochemical resources.Cellulose esters are extremely commercially important materials of biomass derivatives with a wide application in the field of plastics,film,textile,coatings,and pharmacy industries.Cellulose is the most abundant natural polymer on earth and an important resource.The cellulose derivatives are also renewable,biodegradable and biocompatible.The design and preparation of materials using cellulose as raw material has become a trend in the future.In this work,the effects of ionic liquids on cellulose and lipase-catalyzed synthesis of cellulose esters in mixed ionic liquids as well as their application in drug delivery were investigated,which provide theory for the biological modification of cellulose and widen the application of cellulose.The effects of ionic liquids on cellulose consist of dissolution and decomposition were investigated.1-butyl-3-methylimidazolium chloride?[BMIm]Cl?and 1-allyl-3-methylimidazolium chloride?[AMIm]Cl?could dissolve cellulose while 1-butyl-3-methyl-imidazolium tetraflouroborate?[BMIm]BF₄?and 1-butyl-3-methylimidazolium hexafluorophosphate?[BMIm]PF₆?could not.Interesting phenomenon was found that hydrogen sulphate ionic liquids such as 1-butyl-3-methylimidazolium phosphate?[BMIm]HSO₄?could decompose cellulose to cellulose nanocrystalline?CNCs?.Lipase-catalyzed synthesis of cellulose esters consist of long chain cellulose ester?LCCE?and esterified cellulose nanocrystalline?E-CNCs?in ionic liquids were established.According to the above experiments,the method of synthesis of LCCE was proposed.Lipase-catalyzed synthesis of LCCE was investigated in ionic liquids mixtures consisting of [BMIm]Cl and [BMIm]BF₄.Optimum modification conditions for maximum degree of substitute?DS 1.452?of LCCE were shown as following: microcrystalline cellulose?MCC?0.5 g,[BMIm]Cl/[BMIm]BF₄ 6:4,mass ratio of lipase/cellulose 4:20,molar ratio of methyl palmitate/anhydroglucose units?AGU?3:1,reaction temperature 50 ?,transesterification time 3 h.Enzymatic synthesis of E-CNCs was proposed in ionic liquids consist of [BMIm]HSO₄ and [BMIm]BF₄,without the separation of CNCs.The obtained maximum DS value of E-CNCs was 0.163 under the following conditions: MCC 0.3 g,[BMIm]HSO₄ 3 g,[BMIm]BF₄ 5 g,mass ratio of lipase/cellulose 2:10,molar ratio of methyl laurate/anhydroglucose units?AGU?11:1,reaction temperature 50 ?,transesterification time 6 h.Various analytical instruments such as FT-IR,1H NMR,13 C NMR,SEM,TEM,XRD and TG were introduced to investigate the properties of LCCE and E-CNCs.The formation of cellulose esters were confirmed by the presence of the carbonyl signal and acyl group in the FT-IR and NMR spectra.X-ray diffraction data showed that the crystallinity of LCCE was largely disrupted during modification and the cellulose I converted to cellulose II,with crystallization being decreased.While the crystallinity of E-CNCs were similar to MCC and the crystallinity index of E-CNCs were larger than MCC.The morphological properties of MCC and LCCE were illustrated in SEM images and MCC was rod shaped with various sizes,while LCCE exhibited quite different morphology with a granule form with different sizes.The morphology of CNCs and E-CNCs exhibited rod-like shapes with the width range from 10 to 30 nm and the E-CNCs rods could be observed in some places while they were separated in others.TG analysis suggested thermal stability of LCCE and E-CNCs decreased compared to MCC.The new mucoadhesive films for topical administration in the oral cavity have been developed,using shellac as backing layer.The LCCE/E-CNCs,PEG and shellac composites were used as the drug carrier.The films were evaluated for their properties.The films exhibit promising controlled drug release,thus it can be selected to develop the buccal film for effective therapeutic uses.LCCE/E-CNCs may be considered as a potential candidate for the mucoadhesive film drug carrier.