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Dextran-b-poly(L-histidine) copolymer nanoparticles for pH-responsive drug delivery to tumor cells

Authors Hwang JH, Choi CW, Kim HW, Kim DH, Kwak TW, Lee HM, Kim CH, Chung CW, Jeong YI, Kang DH

Received 4 June 2013

Accepted for publication 23 July 2013

Published 21 August 2013 Volume 2013:8(1) Pages 3197—3207

DOI https://doi.org/10.2147/IJN.S49459

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Jong-Ho Hwang,1,2 Cheol Woong Choi,1 Hyung-Wook Kim,1 Do Hyung Kim,3 Tae Won Kwak,3 Hye Myeong Lee,3 Cy Hyun Kim,3 Chung Wook Chung,3 Young-Il Jeong,3 Dae Hwan Kang1,3

1Department of Internal Medicine, Medical Research Institute, Pusan National University School of Medicine, Yangsan, Republic of Korea; 2Department of Internal Medicine, Busan Medical Center, Yeonje-gu, Busan, Republic of Korea; 3National Research and Development Center for Hepatobiliary Disease, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea

Purpose: Nanoparticles based on stimuli-sensitive drug delivery have been extensively investigated for tumor targeting. Among them, pH-responsive drug targeting using pH-sensitive polymers has attracted attention because solid tumors have an acidic environment. A dextran-b-poly(L-histidine) (DexPHS) copolymer was synthesized and pH-responsive nanoparticles were fabricated for drug targeting.
Methods and results: A DexPHS block copolymer was synthesized by attaching the reductive end of dextran to the amine groups of poly(L-histidine). pH-responsive nanoparticles incorporating doxorubicin were fabricated and studied in HuCC-T1 cholangiocarcinoma cells. Synthesis of DexPHS was confirmed by 1H nuclear magnetic resonance spectroscopy, with specific peaks of dextran and PHS observed at 2–5 ppm and 7.4–9.0 ppm, respectively. DexPHS nanoparticles showed changes in particle size with pH sensitivity, ie, the size of the nanoparticles increased at an acidic pH and decreased at a basic pH. DexPHS block copolymer nanoparticles incorporating doxorubicin were prepared using the nanoprecipitation dialysis method. The doxorubicin release rate was increased at acidic pH compared with basic pH, indicating that DexPHS nanoparticles have pH-sensitive properties and that drug release can be controlled by variations in pH. The antitumor activity of DexPHS nanoparticles incorporating doxorubicin were studied using HuCC-T1 cholangiocarcinoma cells. Viability was decreased in cells treated with nanoparticles at acidic pH, whereas cell viability in response to treatment with doxorubicin did not vary according to changes of pH.
Conclusion: Our results indicated that DexPHS polymeric micelles are promising candidates for antitumor drug targeting.

Keywords: pH-responsive drug targeting, nanoparticles, block copolymer, poly(L-histidine), dextran

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