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

Title
Robust PEGylated hyaluronic acid nanoparticles as the carrier of doxorubicin: Mineralization and its effect on tumor targetability in vivo
Authors
Hwa Seung HanJungmin LeeHyun Ryoung KimSu Young ChaeMinwoo KimGurusamy Saravanakumar윤홍열유동길Hyewon Ko김광명권익찬Jae Chan Park박재형
Keywords
Mineralization; Hyaluronic acid; Nanoparticles; Doxorubicin; Stability
Issue Date
2013-06
Publisher
Journal of controlled release
Citation
VOL 168, NO 2, 105-114
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.
URI
http://pubs.kist.re.kr/handle/201004/46383
ISSN
01683659
Appears in Collections:
KIST Publication > Article
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