Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo

Hwa Seung Han, Jungmin Lee, Hyun Ryoung Kim, Su Young Chae, Minwoo Kim, Gurusamy Saravanakumar, Hong Yeol Yoon, Dong Gil You, Hyewon Ko, Kwangmeyung Kim, Ick Chan Kwon, Jae Chan Park, Jae Hyung Park

Research output: Contribution to journalArticlepeer-review

76 Citations (Scopus)

Abstract

The in vivo stability and tumor targetability of self-assembled polymeric nanoparticles are crucial for effective drug delivery. In this study, to develop biostable nanoparticles with high tumor targetability, poly(ethylene glycol)-conjugated hyaluronic acid nanoparticles (PEG-HANPs) were mineralized through controlled deposition of inorganic calcium and phosphate ions on the nanoparticular shell via a sequential addition method. The resulting nanoparticles (M-PEG-HANPs) had a smaller size (153.7 ± 4.5 nm) than bare PEG-HANPs (265.1 ± 9.5 nm), implying that mineralization allows the formation of compact nanoparticles. Interestingly, when the mineralized nanoparticles were exposed to acidic buffer conditions (< pH 6.5), their sizes increased rapidly due to dissolution of the inorganic minerals. Doxorubicin (DOX), chosen as the model anticancer drug, was effectively encapsulated into the bare and mineralized nanoparticles. For bare PEG-HANPs, DOX was released in a sustained manner and its release rate was not dependent on the pH of the solution. On the other hand, DOX release from M-PEG-HANPs was pH-dependent: i.e. DOX was slowly released from nanoparticles under physiological condition (pH 7.4), whereas its release rates were much higher at mildly acidic environments (< pH 6.5). From in vivo biodistribution study, it was found that M-PEG-HANPs could reach the tumor site more effectively than bare PEG-HANPs. The antitumor efficacy of DOX-loaded nanoparticles was evaluated after systemic administration into the tumor-bearing mice. Of the samples tested, the most effective antitumor efficacy was observed for DOX-loaded M-PEG-HANPs. Overall, these results suggest that M-PEG-HANPs could be a promising carrier for an anticancer drug.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalJournal of Controlled Release
Volume168
Issue number2
DOIs
Publication statusPublished - 2013 Jun 10

Keywords

  • Doxorubicin
  • Hyaluronic acid
  • Mineralization
  • Nanoparticles
  • Stability

ASJC Scopus subject areas

  • Pharmaceutical Science

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