Studies On Nanoparticle Drug Delivery System Combining Cyclodextrins And Chitosan

Chitosan (CS) is used as a bioadhesive polymer since the CS has non-toxic, biodegradable, biocompatible, mucoadhesion and ability to transiently open the tight junctions of the intestinal barrier properties. Cyclodextrin (CD) can form inclusion complexes with a variety of drugs, which can increase solubility, improve chemical and physical stability and/or enhance oral absorption of the drug. According to the advantages of both CD and CS, incorporatting CD into CS nanoparticle (NP) and grafting CD molecules onto CS (CD-g-CS) may lead to a carrier that possesses the cumulative effects of inclusion, size specificity and transport properties of CD and mucoadhesive properties of CS. In this study, we systematically investigated the process ofβ-CD/CS and CD-g-CS NPs. And the physicochemical properties of these nanoparticles were characterized. Ketoprofen (KTP) is as a model drug, and drug release from KTP-loaded CD-g-CS NP in vitro was further investigated.The CS nanoparticles were obtained via ionic gelation method using TPP, which possessed spherical morphology, uniform size (157～576 nm), positive zeta potential (28.72～42.90 mv). With the similar conditions and methods, we obtained theβ-CD/CS nanoparticles, CS/HP-β-CD NPs, CS/SB-β-CD NPs and CS/DM-β-CD NPs,which also possessed spherical morphology demonstrated by TEM. The results indicated that the presence ofβ-CD derivatives had no critical impact in the NPs formation process. However, in all the series prepared, the mean diameter of the NPs varied accordingly to the concentration of CDs added during the preparation process. The results from IR studies and element alanalysis, suggest that CS is the major compound on the surface of the NPs, while CD are strongly associated with the NP matrix. Finally, in vitro stability studies indicated that the presence of CDs in the NP structure can prevent the aggregation of this nanometric carrier system in simulated intestinal fluid.Chitosan bearing pendant cyclodextrin (CD-g-CS) was prepared with CS and 6-OTs-β-CD, which was prepared withβ-CD and TsCl. CD-g-CS NPs were obtained via ionic gelation method using TPP, which possessed spherical morphology, uniform size (202 ～589 nm), positive zeta potential (+23.0～43.0 mv). This study demonstrates that systematic design and modulation of the surface charge, particle size of CD-g-CS NPs can be readily achieved with the right control of critical processing parameters. Drug release in vitro from KTP-loaded CD-g-CS NP was further investigated. The release study indicated this CD-g-CS NPs had controlled-release effect and the degree of drug release from KTP-loaded CD-g-CS NPs was depended on the DS of CD-g-CS and pH of release medium.