Preparation And Drug Release Behavior For Intelligent Hydrogel Based On Calcium-alginate

Sodium alginate(SA) is a kind of polysaccharide anionic polymer with goodbiological compatibility, biodegradable and non-toxic etc. Alginate gel can be easilyobtained in the presence of divalent cations like Ca2+, Fe2+and Zn2+, and it is widelyused in biological engineering and controlled drug delivery systems(CDDS). Sincealginate gel is highly hydrophilic in aqueous medium, gels made from SA is lessstable in water resulted in quick swelling and burst drug release. The presentdissertation is aiming to prepare SA-based gels for controlled drug release withimproved swelling and release characteristcs. The main results are mainly as follows:1. Aiming to improve the mechanical stability of alginate gel, a naturepolysaccharides agar is selected as a modified agent to prepare compositealginate/agar gel beads (AALB). The obtained AALB show greatly improvedmechanical stability as compared with the single alginate gel beads (ALB), morecompact surface and internal structures. Swelling and drug release experimentsclearly revealed that the swelling and drug release behaviors are significantlydependent on the agar content, as well as environmental temperature and pH. Drugrelease from AALBs is found to be retarded and the swelling rate of AALBs becamelower than that of ALB under neutral condition.2. Chitosan (CS) is easily crosslinked by sodium polyphosphate(SPPP). By usingthis characteristic of CS, a serials of composite alginate(nucleus)/chitosan(shell) beads(CALB) with controlled chitosan shell are prepared. The obtained CALB arecharacterize by digital camera, SEM, FTIR techniques, the swelling and drug releasebehavior are studied at37oC and in PBS of pH7.4and HCl solution of pH2.1. It isrealized that with the increase in CS content, surface coated CS layer became thicker,which can effectively improve the mechanical stability of CALBs in PBS of pH7.4resulted in a reduced swelling rate and a drug release rate.3. In order to improve the characteristics of single chitosan gel beads (CSB) suchas mechanical stability, swelling and drug release behavior, under acid condition.Alginate is used as the modified agent to prepare a serials of compositealginate(shell)/chitosan(nuclues) beads (ACSB) with controlled alginate gel shell.Some factors affected the shell thickness of ACSB are discussed by orthogonalexperimental method. The obtained ACSBs are characterized with digital camera, SEM, FTIR techniques. The optimization of ACSBs with different shell thicknessshell microspheres are used to studied the swelling and drug release behavior at37oCand in PBS of pH7.4and HCl solution of pH2.1. Results show that the concentrationof CaCl2and crosslinking time are two main factors affecting the shell thickness,which can effectively improve the mechanical stability of ACSBs in simulatedstomach fluid of pH2.1, resulted in a reduced swelling rate and a drug release rate.4. Microgels have gained considerable attention in recent years as one of themost promising nanoparticulate drug delivery systems owing to their uniquepotentials via combining microgel’s hydrophilicity and extremely high water contentwith a nanosize scale. In order to extend the hydrogel in more extend field, a serials ofpH/temperature dual-sensitive alginate/poly (N-isopropylacrylamide)(alginate/PNIPAm) microgel are prepared. The obtained microgel beads arecharacterized by using FTIR, the microgel particle size and particle size distributionare determined by using laser particle size analyzer. The swelling and drug releasebehaviors are measured at different temperature and pH value. The results show thatthe microgel size is largely affected by the ratio water to oil and stirring speed, thehigher the ratio water and the greater the stirring speed, the smaller the microgel size.The swelling and drug release behavior are affected on the gel size, the swelling anddrug release rate tend to increase with reducing the microgel size. The swelling andthe drug release behavior responsed to both pH value and temperature.