Preparation And Properties Of Injectable Functional Hydrogels Enhanced By Tunicate Nanocellulose

In the process of cancer treatment,traditional single chemotherapy drugs have low bioavailability and easy to produce multi-drug resistance.Therefore,a combination of drugs is often used clinically.There is a synergistic treatment effect between multiple drugs,which can appropriately enhance the curative effect of the drug while reducing the toxic and side effects of the drug.The hydrogel has a series of unique properties due to its unique three-dimensional network porous structure,such as it can absorb a large amount of water without affecting its own structure,good biocompatibility,good biodegradability,and responsiveness to various external stimuli,biomimetic,etc..Hydrogels have been widely studied and applied in food industry,tissue engineering,in vivo drug delivery and other fields.Especially in the treatment of cancer,hydrogels can be implanted in the body at fixed points and controlled release of drugs.However,due to the poor mechanical strength and the lack of self-healing function of traditional hydrogel materials,it is difficult to repair the damaged hydrogel implanted into human body after extensive surgical trauma This shortcoming not only shortens the service life of the material,but also hides hidden dangers that threaten the life safety of patientsCellulose is one of the renewable bioenergy sources with the highest reserves and the most extensive sources in the world,because of its unique reinforcement structure,excellent biocompatibility and degradability,is often used as a reinforcement of composite materials.Halocynthia roretzi Drasche is a kind of animal that lives in the shallow sea floor and has been introduced into breeding in recent years.Because only the internal organs are eaten,the tunicate is wasted.In order to reduce environmental pollution and improve economic benefits,the extraction of Halocynthia roretzi Drasche nanocellulose(TCNCs)from the tunicate of Halocynthia roretzi Drasche through some specific means has also become a research hotspot in recent years.TCNCs have a size of tens of nanometers to hundreds of nanometers of nanocellulose,compared to nanocellulose derived from plants and bacteria,TCNCs show a greater aspect ratio and higher Young’s modulus.Therefore,it is widely used to enhance the mechanical strength of composite materials.Compared with traditional hydrogels,injectable hydrogels are injected into the body through a syringe to form drug-loaded hydrogels in situ at the injection site.It has the advantages of little trauma,easy operation,local administration and long-acting drug release.Therefore,it is of great significance to explore and develop injectable hydrogels with self-healing and high mechanical strength to solve the problem of damage repair of flexible biomaterials,avoid highly traumatic surgery,and achieve targeted therapy of tumor diseases and long-term treatment of chronic diseases.In this paper,TCNCs were prepared by sulfuric acid hydrolysis,which was applied to an injectable hydrogel with high mechanical strength and self-healing properties.The specific contents are as follows1.Halocynthia roretzi Drasche was defatted,decolorized and hydrolyzed with concentrated sulfuric acid to obtain the TCNCs suspension with good dispersion,and the white flocculent solid was obtained after freeze-drying treatment.The structure of TCNCs was characterized and analyzed by visual inspection and scanning electron microscopy(SEM),Fourier transform infrared spectroscopy(FTIR),thermogravimetric analysis(TGA),X-ray diffraction(XRD).The results showed that TCNCs have good dispersion in deionized water(DW),and it was not precipitated or agglomerated after being placed for a long time.SEM analysis showed that TCNCs presented a regular rod-like structure with a length-diameter ratio of about 36.FTIR analysis found that TCNCs have similar chemical structure with cellulose,indicating that hydrolysis have no significant effect on the chemical structure of TCNCs.TGA showed that the nanocellulose have higher thermal decomposition temperature.XRD analysis showed that TCNCs have similar crystal structure and higher crystallinity than cellulose.2.Under the action of Dess-Martin oxidant,Pluronic(?)F127 synthesizes PF127-CHO by one-step oxidation,and then uses physical embedding method to prepare curcumin(CUR)loaded PF127-CHO-CUR.The chemical structures of PF127-CHO and PF127-CHO-CUR were characterized by FTIR,nuclear magnetic hydrogen spectroscopy(1H-NMR)and dynamic light scattering(DLS).FTIR and 1H-NMR proved the successful synthesis of PF127-CHO,and DLS proved the success of CUR Load into PF127-CHO-CUR.Chitosan(CS)solution,TCNCs suspension and aldehyde-sealed Pluronic█ F127(PF127-CHO)solution were mixed under physiological conditions,and a series of TPC hydrogels were prepared by physical crosslinking and chemical crosslinking.The microstructure,chemical structure and thermal stability of TPC hydrogels were characterized by SEM,FTIR and TGA.Vision method and rheological test show that TPC hydrogels have excellent self-healing and good mechanical strength.The injectability of TPC hydrogels were verified by in vitro injection experiment.The degradation behavior test showed that TPC hydrogels have good pH sensitivity and good biodegradability.The micromorphology,chemical structure and thermal stability of TPC hydrogels were characterized by SEM,FTIR and TGA.Macroscopic observations and rheological mechanical tests proved that TPC hydrogels have excellent self-healing properties and good mechanical strength.The injectability of TPC hydrogels was verified by in vitro injection experiments.The degradation behavior test showed that TPC hydrogels have good pH sensitivity and good biodegradability.In addition,the in vitro release behavior of doxorubicin(DOX)and curcumin(CUR)as model drugs showed that in an acidic environment,the release rate and release amount of the drug are greater,and with the change of PF127-CHO content,the release efficiency will also change.The cytotoxicity test of the blank hydrogel confirmed its good biocompatibility.In contrast,drug-loaded hydrogels were highly cytotoxic to tumor cells.All in all,TPC hydrogels had good application prospects in drug delivery vehicles for in vivo tumor therapy.