Construction Of Chitosan-based Photoresponsive Drug Delivery Systems And Their Performance

To achieve the purpose of efficient treatment,it is urgent to develop the delivery vehicle for the controlled release of the drug.However,traditional drug delivery systems have problems such as slow drug release,poor selectivity,and low drug utilization.Thus,there is a need to develop smart delivery systems responding to environmental stimuli.Herein,photo-responsive delivery systems with good biocompatibility were developed based on natural polysaccharide of chitosan combined with photosensitive monomers.Main research contents and resu Lts are as follows:(1)Construction of chitosan-based photo-responsive drug releasing hydrogel dressings:Initially a photo-sensitive monomer cross-linking agent was linked to polyethylene glycol(PEG)and chitosan was modified.The photo-responsive hydrogel was prepared by combining PEG-photosensitive monomer with methacrylic acid-modified chitosan and N-isopropylacrylamide(NIPAM).The FTIR,NMR and TGA results indicate that methacrylic acid was successfu Lly grafted to the amino group of chitosan,and the photo-responsive hydrogel is successfu L prepared.SEM characterization results showed that the prepared photosensitive hydrogel presents a typical pore structure and the pore density increases with the increase of PEG-photosensitive monomer crosslinking agent.The compression test further shows that the mechanical properties of the hydrogel are improved with the increase of NIPAM and PEG-photosensitive monomer crosslinking agent.The swelling analysis indicates the excellent swelling properties of the hydrogel.Doxorubicin(DOX)and bovine serum albumin(BSA)were used as model drugs.It is found that the prepared hydrogel can achieve controlled release under photo irradiation.In addition,the prepared hydrogel dressing exhibit antibacterial capacity.(2)Construction of chitosan-based photo controlled drug release micelles:firstly,the photosensitive monomer was modified with succinic anhydride to obtain the anionic photosensitive monomer(SA-ONB ester).The NMR and UV characterization prove that the photosensitive monomer was successfully modified by succinic anhydride.Then the SA-ONB ester dissolved in tetrahydrofuran(THF)was mixed with cationic chitosan,and micelles were prepared by ultrasound.The size of micelles is dependent on the ultrasound time,the mass ratio of chitosan to SA-ONB ester and the content of THF.Increasing the ultrasound time leads to a slight increase in the particle size but results in a decrease in the polydispersity index(PDI).Decreasing the mass ratio of chitosan to SA-ONB ester causes a gradual increase in the micelle size.Furthermore,reduction in the THF leads to a decrease in the particle size but a rise in the zeta potential,resulting in the stability of the micelles.In-vitro experiments proved that the micellar cells are less toxic.The photosensitivity experiment shows that around 80%of Nile Red encapsulated can be released when the irradiation intensity of 5 m W/cm~2 and 10 m W/cm~2 are applied for 300 and 100 s,respectively,indicating that the system can achieve rapid drug release.(3)Construction of chitosan-based in situ injectable photo controlled drug release hydrogel:Oxidized sodium alginate(OSA)was obtained by oxidizing sodium alginate.OSA/CMCS hydrogel system was formed through the Schiff base reaction between OSA and carboxymethyl chitosan(CMCS).FTIR results reveal the successful preparation of OSA and the hydrogel of OSA/CMCS.In order to further construct an injectable photo-controlled drug delivery system,a dual-network hydrogel system was prepared by mixing PEG-ONB photocrosslinking agent and NIPAM and further reacting with OSA/CMCS.Compared with OSA/CMCS hydrogel,the introduction of PEG-ON-NIPAM network effectively improves the mechanical properties which is able to self-heal in a humid environment.Under UV irradiation,the hydrogel degradation was clearly observed.The rheological analysis further show that the system has good shear thinning ability.Drug release studies show that the photo stimuli leads to changes in the hydrogel property,further casusing faster drug release.