Development of new ionic gelation strategy： Towards the preparation of new monodisperse and stable hyaluronic acid/ β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin

In the present study, β-cyclodextrin-grafted chitosan nanoparticles （β-CD- g-CS NPs） were prepared using a new ionic gelation strategy involving a synergistic effect of NaCI （150 mmol/L）, 4-（2-hydroxyethyl）-1-piperazineethanesulfonic acid （HEPES, 10 mmol/L）, and water bath sonication. This new strategy afforded smaller and more monodisperse β-CD-g-CS NPs vs. the classical ionic gelation method. New HA8β-CD-g-CS NPs were also prepared using the above-mentioned strategy by adding hyaluronic acid （HA） to the β-CD-g-CS copolymer at different weight ratios until the ZP values conversion. The best result was obtained with the weight ratio of w（HA）：w（β-CD-g-CS） = 2：1 and furnished new spherical and smooth HA/β-CD-g-CS NPs. Furthermore, the stability of β- CD-g-CS NPs and HA/β-CD-g-CS NPs at 4℃ in physiological medium （pH 7.4） was compared for 3 weeks period and showed that HA/β-CD-g-CS NPs were more stable all maintaining their monodispersity and high negative ZP values compared to β-CD-g-CS NPs. Finally, preliminary study of HA/β-CD-g-CS NPs as carrier for the controlled release of the anticancer drug doxorubicin was investigated. These new HA/β-CD-g-CS NPs can potentially be used as drug delivery and targeting systems for cancer treatment.

Novel nanoparticles composed of chitosan and β-cyclodextrin derivatives as potential insoluble drug carrier

This research was aim to develop novel cyclodextrin/chitosan （CD/CS） nanocarriers for insoluble drug delivery through the mild ionic gelation method previously developed by our lab. A series of different β- cyclodextrin （β-CD） derivatives were incorporated into CS nanoparticles including hydroxypropyl-β- cyclodextrin （HP-β-CD）, sulphobutylether-β-cyclodextrin （SB-β-CD）, and 2,6-di-O-methy-βcyclodex- trin （DM-β-CD）. Various process parameters for nanoparticle preparation and their effects on physicochemical properties of CD/CS nanoparticles were investigated, such as the type of CD derivatives, CD and CS concentrations, the mass ratio of CS to TPP （CS/TRP）, and pH values. In the optimal condition, CDICS nanoparticles were obtained in the size range of 215-276 nm and with the zeta potential from 30.22 mV to 35.79 mY. Moreover, the stability study showed that the incorporation of CD rendered the CD/CS nanocarriers more stable than CS nanoparticles in PBS buffer at pH 6.8. For their easy preparation and adjustable parameters in nanoparticle formation as well as the diversified hydrophobic core of CD derivatives, the novel CD/CS nanoparticles developed herein might represent an interesting and versatile drug delivery platform for a variety of poorly water-soluble drugs with different physicochemical properties.