Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery

• Main Authors: Hock Ing Chiu, Asila Dinie Ayub, Siti Nur Aishah Mat Yusuf, Noorfatimah Yahaya, Erazuliana Abd Kadir, Vuanghao Lim
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: Pharmaceutics
• Subjects: disulfide cross-linked nanoparticles; thiolated sodium alginate; wheat germ agglutinin conjugation; ht-29; docetaxel
• Online Access: https://www.mdpi.com/1999-4923/12/1/38

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.