Synthesis, Formulation, and Characterization of Doxorubicin-Loaded Laponite/Oligomeric Hyaluronic Acid-Aminophenylboronic Acid Nanohybrids and Cytological Evaluation against MCF-7 Breast Cancer Cells

Abstract

As a synthetic clay material, laponite RDS (LR) was investigated as an effective drug carrier as a result of the special nanodisk structure together with the negative-charged surface to achieve enhanced cellular uptake and targeted delivery. In this research work, the synthesized oligomeric hyaluronic acid-aminophenylboronic acid (oHA-APBA) was entangled onto LR nanodisks to fabricate a valid targeted platform for breast cancer therapy. Briefly, through the formation of amide bonds, 3-APBA was connected to the chain of oHA with a substituted ratio of 4.0 ± 0.2% to synthesize oHA-APBA copolymer. Thereafter, doxorubicin (DOX) was inserted into the interlayer space of LR by the way of the ion exchange process, followed by an assembly with oHA-APBA as a targeted protection layer. The satisfactory drug encapsulation efficiency (> 80%) and narrow size distribution were achieved. The in vitro drug release study demonstrated the release of DOX from DOX@LR/oHA-APBA was sustained and acid dependent. In addition, after fitting the drug cumulative release of DOX@LR/oHA-APBA under different pH conditions with several kinetic models, it was identified that drug release from DOX@LR/oHA-APBA nanohybrids at pH 5.0 was mainly dependent on both diffusion and ion exchange effects. However, under the condition of pH 7.4, the drug was most efficiently released by diffusion effect. Importantly, DOX@LR/oHA-APBA showed remarkable cellular uptake and intracellular drug distribution in MCF-7 cells, which were consistent with inhibitory ability against MCF-7 cells. Hence, the high DOX loading capacity and enhanced cellular tracking can enlighten LR/oHA-APBA as an effective drug delivery carrier for breast cancer therapy.

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Funding

This work was supported by the National Natural Science Foundation Youth Science Foundation Project (81703709) and project funded by China Postdoctoral Science Foundation (2018M641716).

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Correspondence to Weisan Pan.

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Yang, Y., Li, J., Chen, F. et al. Synthesis, Formulation, and Characterization of Doxorubicin-Loaded Laponite/Oligomeric Hyaluronic Acid-Aminophenylboronic Acid Nanohybrids and Cytological Evaluation against MCF-7 Breast Cancer Cells. AAPS PharmSciTech 21, 5 (2020). https://doi.org/10.1208/s12249-019-1533-6

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KEY WORDS

  • laponite RDS
  • targeted delivery
  • oligomeric hyaluronic acid
  • 3-aminophenylboronic acid
  • breast cancer therapy