Preparation Of Lysine Modified Nanocellulose-based Hydrogel And Its Application In Indomethacin Sustained Release

Absorption of oral drugs is a slow process,but traditional drug carriers often cause rapid corrosion after oral administration,which can lead to sudden release of drugs and cause injury to the human gastrointestinal tract and nervous system.Therefore,the study of a new type of carrier material that can solve the problems of traditional drug carriers has become the current research hotspot.The nanocellulose which is abundant with the characteristics of biodegradability and high biocompatibility exposes a large number of hydroxyl groups to make it easy to be modified.Therefore it has the potential to be used as a drug carrier in drug delivery,wound repairing,and other medical fields.In this paper,after the processes of neutral TEMPO/NaClO/NaClO₂ microwave oxidation,high pressure homogenization,sodium periodate selective oxidation,and Schiff base reaction,modified nanofibers?NFC-m-Lysine?containing both amino and carboxyl groups were obtained from softwood pulp boards.Then,a cationic guar gum and lysine modified nanocellulose hybrid hydrogel?CGG/NFC-m-Lysine hydrogel?was prepared with cationic guar gum and NFC-m-Lysine.A simple method based on in-situ sample pretreatment and headspace-gas chromatography?HS-GC?method for determination of lysine was developed during the reaction of Schiff base.It turns out that the CGG/NFC-m-Lysine hydrogel is pH-sensitive,and the release of indomethacin is in accordance with the Korsmeyer-Peppas model.The main contents and results of the study are as follows:?1?The cellulose carboxyl content after the TEMPO oxidation was 1.1 mmol/g,the content aldehyde group of aldehyde intermediates--dialdehyde-based nanocellulose after oxidated by sodium periodate for 13 hours was 3.37 mmol/g and the nitrogen content of the NFC-m-Lysine product was 3.6%?DMSO:water=9:1?.FT-IR,TG and TEM analysis confirmed the successful introduction of-NH₂ and the modified NFC has better thermal stability after the introduction of amino group.Zeta potential measured that the nanocellulose diameter was around 50 nm and length was no more than 1000 nm.The presence of amino and carboxyl groups enables functionalized nanocellulose to behave differently when pH varys.?2?The optimal reaction conditions for the determination of lysine concentration by HS-GC method were ninhydrin/lysine molar ratio 16,equilibrium temperature 60°C,equilibrium time 60 min and pH 4.0.Compared with the conventional ninhydrin colorimetric method,the relative error is less than 6.8%.The advantage of short time and high efficiency of the HS-GC method is particularly suitable for batch detection of lysine samples.By the method,the Schiff base reaction time was determined to be 5 h,the reaction pH was 11.8,the reaction temperature was 40°C,and the conversion rate of lysine was 90%.?3?The CGG/NFC-m-Lysine hydrogel prepared from CGG and NFC-m-Lysine is pH-sensitive macroporous ionic hydrogel.The results of SEM,TG,FT-IR and XRD analysis showed that indomethacin?IND?was successfully loaded onto the hydrogel and existed as an amorphous state.The pore diameter of the CGG hydrogel was range from 100?m and 300?m.Compared with CGG hydrogel,the pore size of CGG/NFC-m-Lysine hydrogel is more uniform and the diameter is about 100?m.The addition of NFC and NFC-m-Lysine reduces the thermal stability of the hydrogel.?4?The CGG/NFC-m-Lysine hydrogel improved the burst behavior of CGG hydrogels.The release of IND in mediun at pH 6.8 and 7.4 sustained for 12 hours,and the release rate were 95.68%and 84.77%,respectively.About 75.15%of IND was released at 49 h while released in the strongly acidic release medium.The mechanism of controlled release is well-fitted to the Korsmeyer-Peppas model,but the diffusion pattern of the IND is different under different pH conditions.The diffusion of IND from the hydrogel network structure to medium at pH 1.2 is limited by non-Fickian diffusion,whereas the diffusion from the medium at pH 6.8 and pH 7.4 is limited by Fickian diffusion.