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Open AccessArticle

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

1
Integrative Medicine Cluster, Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia
2
Department of Chemical Engineering Technology, Faculty of Engineering Technology, Universiti Malaysia Perlis, UniCITI Alam Campus, 02100 Padang Besar, Perlis 02600, Malaysia
3
Department of Chemistry, University of British Columbia, Vancouver, BC V6T 1Z1, Canada
4
School of Agriculture and Food Sciences, The University of Queensland, Brisbane, St Lucia 4072, Australia
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 38; https://doi.org/10.3390/pharmaceutics12010038
Received: 8 October 2019 / Revised: 26 November 2019 / Accepted: 28 November 2019 / Published: 2 January 2020
(This article belongs to the Special Issue Nanocarriers for Drug Delivery Systems)
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. View Full-Text
Keywords: disulfide cross-linked nanoparticles; thiolated sodium alginate; wheat germ agglutinin conjugation; HT-29; docetaxel disulfide cross-linked nanoparticles; thiolated sodium alginate; wheat germ agglutinin conjugation; HT-29; docetaxel
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MDPI and ACS Style

Chiu, H.I.; Ayub, A.D.; Mat Yusuf, S.N.A.; Yahaya, N.; Abd Kadir, E.; Lim, V. Docetaxel-Loaded Disulfide Cross-Linked Nanoparticles Derived from Thiolated Sodium Alginate for Colon Cancer Drug Delivery. Pharmaceutics 2020, 12, 38.

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