Hyaluronan–cisplatin conjugate nanoparticles embedded in Eudragit S100-coated pectin/alginate microbeads for colon drug delivery

Abstract

Shiao-Wen Tsai,1 Ding-Syuan Yu,2 Shu-Wei Tsao,1 Fu-Yin Hsu2,3 1Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan; 2Department of Life Science, 3Institute of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung, Taiwan Abstract: Hyaluronan–cisplatin conjugate nanoparticles (HCNPs) were chosen as colon-targeting drug-delivery carriers due to the observation that a variety of malignant tumors overexpress hyaluronan receptors. HCNPs were prepared by mixing cisplatin with a hyaluronan solution, followed by dialysis to remove trace elements. The cells treated with HCNPs showed significantly lower viability than those treated with cisplatin alone. HCNPs were entrapped in Eudragit S100-coated pectinate/alginate microbeads (PAMs) by using an electrospray method and a polyelectrolyte multilayer-coating technique in aqueous solution. The release profile of HCNPs from Eudragit S100-coated HCNP-PAMs was pH-dependent. The percentage of 24-hour drug release was approximately 25.1% and 39.7% in pH 1.2 and pH 4.5 media, respectively. However, the percentage of drug released quickly rose to 75.6% at pH 7.4. Moreover, the result of an in vivo nephrotoxicity study demonstrated that Eudragit S100-coated HCNP-PAMs treatment could mitigate the nephrotoxicity that resulted from cisplatin. From these results, it can be concluded that Eudragit S100-coated HCNP-PAMs are promising carriers for colon-specific drug delivery. Keywords: hyaluronan, cisplatin, pectin, alginate, pH-dependent, drug delivery