Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery
Hock Ing Chiu, Asila Dinie Ayub, Siti Nur Aishah Mat Yusuf, Noorfatimah Yahaya, Erazuliana Abd Kadir, Vuanghao Lim
Abstract
In this study, fluorescein-labelled wheat germ agglutinin (fWGA)-conjugated disulfide cross-linked sodium alginate nanoparticles were developed to specifically target docetaxel (DTX) to colon cancer cells. Different amounts of 3-mercaptopropionic acid (MPA) were covalently attached to sodium alginate to form thiolated sodium alginate (MPA1-5). These polymers were then self-assembled and air-oxidised to form disulfide cross-linked nanoparticles (MP1-5) under sonication. DTX was successfully loaded into the resulting MP1-5 to form DTX-loaded nanoparticles (DMP1-5). DMP2 had the highest loading efficiency (17.8%), thus was chosen for fWGA surface conjugation to form fWGA-conjugated nanoparticles (fDMP2) with a conjugation efficiency of 14.1%. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses showed spherical nanoparticles, and an in vitro drug release study recorded a cumulative drug release of 48.6%. Dynamic light scattering (DLS) analysis revealed a mean diameter (MD) of 289 nm with a polydispersity index (PDI) of 0.3 and a zeta potential of -2.2 mV for fDMP2. HT-29 human colon cancer cells treated with fDMP2 showed lower viability than that of L929 mouse fibroblast cells. These results indicate that fDMP2 was efficiently taken up by HT-29 cells (29.9%). Fluorescence and confocal imaging analyses also showed possible internalisation of nanoparticles by HT-29 cells. In conclusion, fDMP2 shows promise as a DTX carrier for colon cancer drug delivery.