Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system

Ndumiso Vukile Mdlovu; Kuen-Song Lin; Meng-Tzu Weng; You-Sheng Lin

doi:10.1016/j.colsurfb.2021.112168

Design of doxorubicin encapsulated pH-/thermo-responsive and cationic shell-crosslinked magnetic drug delivery system

Colloids Surf B Biointerfaces. 2022 Jan;209(Pt 2):112168. doi: 10.1016/j.colsurfb.2021.112168. Epub 2021 Oct 21.

Authors

Ndumiso Vukile Mdlovu¹, Kuen-Song Lin², Meng-Tzu Weng³, You-Sheng Lin¹

Affiliations

¹ Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li District, Taoyuan City 32003, Taiwan.
² Department of Chemical Engineering and Materials Science, Yuan Ze University, Chung-Li District, Taoyuan City 32003, Taiwan. Electronic address: kslin@saturn.yzu.edu.tw.
³ Department of Internal Medicine, National Taiwan University Hospital, Taipei 100233, Taiwan. Electronic address: wengmengtzu@gmail.com.

PMID: 34715504
DOI: 10.1016/j.colsurfb.2021.112168

Abstract

The upsurge in cancer cases, such as liver cancer, has claimed millions of lives globally and has prompted the development of novel nanodrug delivery systems. These systems allow cancer drugs to be encapsulated in nanocarriers and delivered to tumor sites, and accordingly, help reduce side effects of the current chemotherapeutic treatments. Herein, we prepared nanocarriers comprising magnetic iron oxide (MIO) nanoparticles that were surface modified with crosslinked Pluronic F127 (PF127) and branched polyethylenimine (bPEI) to form MIOpoly nanocarriers. These nanocarriers were then loaded with doxorubicin (DOX) anticancer drug to form the MIOpoly-DOX complex. The nanocarriers were magnetite and possessed superparamagnetic properties. Small-angle neutron scattering (SANS) analysis indicated that the nanocarriers were thermoresponsive and spherically structured. The characteristic peaks at 1285, 1619, 2844, 2919, 2900, 2840, and 3426 cm^-1, corresponding to those of CN, -NH₂, -CH₂, and OH-, confirmed the successful crosslinking, coating of PF127-bPEI polymers on the surface of MIO nanoparticles and DOX conjugation. The bioavailability of the nanocarriers indicated a more than 85% cell viability when using HepG2 liver cancer cells. A pH (54.8% release in 48 h; pH = 5.4) and temperature (51.0% release in 48 h; 42 °C)-dependent release of DOX was observed, displaying a Korsmeyer-Peppas kinetics model at low pH and Weibull model at high temperatures. The high DOX fluorescence observed for MIOpoly-DOX indicated a high cellular uptake enhanced by alternating magnetic field. These results suggest that MIOpoly synthesized using a combined approach of surface crosslinking and grafted with PF127-bPEI appear to offer promising properties as drug delivery system. Therefore, the nanocarriers developed in the study possess a great potential for targeted delivery and thereby circumventing the limitations of conventional chemotherapy.

Keywords: Cationic-magnetic nanocarriers; Doxorubicin; Drug delivery system; Liver cancer; pH-/thermo-responsive.

MeSH terms

Antineoplastic Agents* / pharmacology
Doxorubicin
Drug Carriers
Drug Delivery Systems
Drug Liberation
Hydrogen-Ion Concentration
Magnetic Fields
Nanoparticles*

Substances

Antineoplastic Agents
Drug Carriers
Doxorubicin