(607a) Doxorubicin-Loaded Poly (lactic-co-glycolic acid) Nanoparticles Coated with Chitosan /Alginate for Antitumor Activity

Authors: 
Sun, L., Wenzhou Institute of Biomaterials and Engineering
Chai, F., China Pharmaceutical University
Li, J., China Pharmaceutical University
Ge, L., China Pharmaceutical University
Webster, T. J., Northeastern University
Zheng, C., China Pharmaceutical University

Introduction

Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are widely used as delivery carriers for anticancer drugs. However, the obvious initial burst release phenomenon of PLGA nanoparticles is unfavorable for anticancer drugs that have significant systemic toxicity as the drug release also needs to be well controlled. To overcome these shortcomings, the objective of the present study was to create multilayered bio-polyelectrolyte chitosan (CHI) and alginate (ALG) composite by a layer by layer (LbL) self-assembly process on the surface of doxorubicin (DOX)-PLGA NPs.

Materials and Methods

DOX (99.41% purity) was purchased from HuaFeng United Technology CO. Ltd, Beijing, China. PLGA 50:50 (Mw 15-20 kDa) was obtained from the Institute of Medical Instruments (Shandong, China). ALG (200 MPa·s) and CHI (Mw 49 kDa) were purchased from Sigma Aldrich.

DOX-PLGA NPs coated with CHI and ALG were prepared by the LbL self-assembly. The influencing factors for multilayer growth and the growth regime of the natural polyelectrolyte multilayer on the PLGA nanoparticles were investigated. A systematic characterization of the coated and bare nanoparticles including TEM (transmission electron microscopy), AFM (atomic force microscopy), zeta potential and XRD (X-ray diffraction) was performed, and the effects of the different layers and medium pH on the controlled release of DOX were also studied. All experiments were completed in triplicate and repeated at least three times. Differences between means were determined using ANOVA followed by standard statistical evaluation.

Results

The weight of the coating of the polyelectrolyte multilayer increased with an increase in polyelectrolyte concentration, NaCl concentration and the coating temperature, 2 mg/mL polyelectrolyte with 0.5 M added NaCl and 37 °C were chosen as the most suitable synthesis. The growth regime of the CHI/ALG multilayer was found to be exponential. A core-shell structure was observed and the ζ-potential switched between positive and negative values during the coating process. The in vitro release behavior demonstrated the undesirable initial burst release of DOX-loaded PLGA nanoparticles (DOX-PLGA NPs) which was significantly relieved through the LbL technique (Figure 1A). Meanwhile, the coated nanoparticles with CHI and ALG showed a pH-dependent characteristic and the release of DOX increased with a decrease in medium pH (Figure 1B).

Conclusions

PLGA nanoparticles coated with CHI/ALG by a LbL process have a potential applications for controlled anti-cancer drug release.

Acknowledgements

This work was financially supported by the Fundamental Research Funds for the Central Universities (no. 2015PT050) and the Natural Science Foundation of China (no. 81402878 and 81473160).