Preparation Of PH Sensitive Chitosan Hydrogel Microspheres For Controlled Drug Delivery

Oral administration is susceptible to gastrointestinal p H,enzyme system and liver first-pass effect,which leads to the decrease of drug utilization and the effect of treatment.Using pH-sensitive hydrogel microcapsules to wrap the drug can effectively solve the above problems.Chitosan（Cs）,sodium alginate（Alg）,carboxymethyl cellulose（CMC）,etc.,with good biocompatibility,degradation,pH sensitivity,and metal ions(Ca²⁺,Fe³⁺,Zn²⁺,etc.)can quickly form hydrogels,widely used in drug delivery systems（DDS）.However,the single drug-loaded microcapsules have poor mechanical properties,strong hydrophilicity,large swelling of water absorption,resulting in drug blasting release,which can not reach the goal of slow release and target.In this paper,four kinds of new core-shell p H-sensitive chitosan-based microcapsules were prepared by means of chemical modification and laminated self-assembly（Layer-by-layer self-assembly,LbL）technique,and the swelling and drug-releasing behaviors of gel microcapsules were improved.At the same time,this paper studies the swelling,p H responsiveness and drug release behavior of gel microcapsules,and emphatically discusses the mechanism of gel microspheres release.The main research contents and results are as follows:1.In order to develop pH-sensitive drug vehicles for colon specific drug delivery by a relatively green and ecofriendly way,natural biopolymers（CMC and Cs）were used in our study.An anticancer drug,5-FU was used as a model drug and loaded into the CMC microcapsules by an ionotropic gelation method.To conquer the weakness of the CMC microcapsules like poor mechanical performance and explosive drug release,ZnO nanoparticles were immobilized into CMC matrix,and then coated with Cs via self-assemble technique to form the PECs through interionic interactions between oppositely charged biopolymers.FT-IR,SEM,TEM,TGA,swelling index,drug loading efficiency and release profiles were investigated.Obtained ZnO@CMC@Cs nanocomposite hydrogel beads with reduced porosity could efficiently encapsulate 43%5-FU and showed self-sustained release behavior.The above all results indicate that the coated nano beads fully exhibit its better pH-sensitive and could be used as a biocompatible and biodegradable carrier for colon specific 5-FU delivery.2.A new p H-sensitive drug carrier based on Alg,Cs and kC marine biopolymers was developed via duel layered PECs microbeads.The structures and thermal stability of developed microcapsules were investigated using FT-IR and TGA respectively,while their morphological changes were studied through SEM examination.Results showed that the stability and swelling degree of Alg microbeads at higher pH 7.4 were enhanced after generation of the duel layered PECs.As well,the vitro release profiles of 5-FU under simulated gastrointestinal conditions were also examined.At gastric conditions（pH 1.2）,the cumulative 5-FU release percentage was affected by the additional kC layer,where it decreased from 14%of single layered Alg/Cs microbeads to 7%for duel layered Alg/Cs/kC microbeads.Moreover,the prepared microbeads were demonstrated their biodegradation ability as well as their cytotoxicity was also evaluated.The gained results clearly suggested that the pH sensitive Alg/Cs/kC microbeads could be promising used effectively for the delivery of anticancer drugs to colon tract.3.A new amphoteric carrier based on Alg and aminated chitosan coated microbeads（Alg@AmCs）was developed for BSA protein drug delivery.The developed microbeads were characterized their structures and thermal stability using FTIR spectroscopy and TGA respectively,while their morphological changes were recognized through SEM examination.Both swelling and BSA release behaviors of the developed microbeads were investigated to evaluate their pH sensitivity at different pH.The presented results indicated that the pH sensitivity was found to have relied on the amount of AmCs in the coating medium.The reviewed results were interpreted from the view of the individual pH sensitivity of both Alg and AmCs in addition to the formed ionic interaction between them under the studied pH.Also,it was noticed that the efficiency of the loaded BSA（LE）exceeded 82%regardless of the initial concentration of BSA.Besides;the in vitro release profiles of BSA under the simulated gastric fluid（SGF;pH 1.2）,simulated intestinal fluid（SGF;pH 6.8）and simulated colonic fluid（SIF;pH 6.8）conditions were discussed.In SGF,the cumulative BSA release percentage of the coated microbeads was slightly affected by increasing amount of AmCs up to 2%（less than 33%）.While approximately 63%and86%were released in SIF and SCF respectively using 0.25%AmCs.On the other hand,the stability of the coated alginate microbeads at SCF was enhanced with increasing AmCs concentration from 0.25%to 2%.Furthermore,the developed microbeads have also demonstrated their ability for biodegradation in addition to their antibacterial activities against selected bacterial strains.The results clearly suggested that the Alg@AmCs coated microbeads could be suitable polymeric carriers for site-specific protein delivery in the intestinal and colon tracts.4.The present study concerns the development of phosphorylated Alg-Cs polyelectrolyte beads as drug delivery and bone regenerative materials.Calcium/phosphate contents and water uptake behavior for the developed beads were optimized by variation of the used calcium chloride,ortho-phosphoric acid（OPA）,and Cs concentrations.Furthermore,the bio-characteristics such as antibacterial activity,biocompatibility,biodegradability and cytotoxicity were evaluated.Moreover,the in vitro drug behavior was studied at different pH using sodium diclofenac（SD）as a model of analgesic drugs.Results revealed that the drug loading efficiency exceeded75%regardless of the initial amount of SD.While the released amount of SD at pH1.2 reached maximum value 45%with increasing Cs concentration up to 1%.On the other hand,approximately 90 and 91%were released at pH6.8 and pH7.2 using0.5 and 0.25%Cs,respectively.The gained results clearly suggested that the developed PsAlg@Cs beads could be effectively applied as suitable biodegradable,non-toxic,bio-compatible carriers for drugs through gastrointestinal tract.