Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and Chitosan for oral delivery of paclitaxel

Jiao Li; Pingsheng Huang; Longlong Chang; Xingwen Long; Anjie Dong; Jinjian Liu; Liping Chu; Fuqiang Hu; Jianfeng Liu; Liandong Deng

Macromolecular Research, Vol.21, No.12, 1331-1337, December, 2013

DOI10.1007/s13233-013-1171-x Export Citation

Tumor targeting and pH-responsive polyelectrolyte complex nanoparticles based on hyaluronic acid-paclitaxel conjugates and Chitosan for oral delivery of paclitaxel

Jiao Li, Pingsheng Huang, Longlong Chang, Xingwen Long, Anjie Dong, Jinjian Liu¹, Liping Chu¹, Fuqiang Hu², Jianfeng Liu^{1, †}, and Liandong Deng^†

School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300072, P. R. China
¹Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, P. R. China
²College of Pharmaceutical Science, Zhejiang University, Hangzhou, 310058, P. R. China

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A new platform of paclitaxel (PTX) for application as an oral delivery system was developed, by combining the pH sensitivity of polyelectrolyte complex nanoparticles (CNPs) and the active targeting of hyaluronic acid (HA). Chitosan/hyaluronic acid-paclitaxel (CS/HA-PTX) CNPs were prepared by coating the CS onto the HA-PTX nanoparticles (NPs), and characterized by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (1H NMR), transmission electron microscopy (TEM) and high-performance liquid chromatography (HPLC). HA-PTX conjugates could self-assemble into NPs in aqueous solution with an average size of 100±5 nm, and the PTX content of HA-PTX conjugates was 10.6 wt%. The CS/HA-PTX CNPs had a smaller size and higher PTX content when the ratio of positive charge to negative charge was 2:1. The in vitro release of PTX from CNPs was pH-responsive, suggesting that the CS shell could prevent the breakage of the ester bond in HA-PTX NPs in acidic pH conditions. HA-PTX NPs exhibited higher cellular uptake than free PTX against HepG2 cells via receptor-mediated endocytosis. PTX could accumulate remarkably into tumor sites after oral administration of CNPs. These results indicate that the CNP drug delivery system has great potential for applications in the oral administration of hydrophobic drugs.

Keywords:polyelectrolyte complex nanoparticles;pH-responsive;tumor targeting;oral administration;hyaluronic acid;paclitaxel

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[Referenced By]

[1] Bromberg L, J. Control. Release, 128, 99 (2008)

[2] Lin YH, Liang HF, Chung CK, Chen MC, Sung HW, Biomaterials, 26, 2105 (2005)

[3] Lin YH, Mi FL, Chen CT, Chang WC, Peng SF, Liang HF, Sung HW, Biomacromolecules, 8(1), 146 (2007)

[4] Gaucher G, Satturwar P, Jones MC, Furtos A, Leroux JC, Eur. J. Pharm. Biopharm., 76, 147 (2010)

[5] Ensign LM, Cone R, Hanes J, Adv. Drug Deliv. Rev., 64, 557 (2012)

[6] Leonelli F, La Bella A, Migneco L, Bettolo R, Molecules, 13, 360 (2008)

[7] Malingre MM, Beijnen JH, Schellens JHM, Invest. New Drugs, 19, 155 (2001)

[8] Breedveld P, Beijnen JH, Schellens JHM, Trends Pharmacol. Sci., 27, 17 (2006)

[9] Fonseca C, Simoes S, Gaspar R, J. Control. Release, 83, 273 (2002)

[10] Vicari L, Musumeci T, Giannone I, Adamo L, Conticello C, De Maria R, Pignatello R, Puglisi G, Gulisano M, BMC Cancer, 8 (2008)

[11] Bachar G, Cohen K, Hod R, Feinmesser R, Mizrachi A, Shpitzer T, Katz O, Peer D, Biomaterials, 32, 4840 (2011)

[12] Rivkin I, Cohen K, Koffler J, Melikhov D, Peer D, Margalit R, Biomaterials, 31, 7106 (2010)

[13] Lee H, Ahn CH, Park TG, Macromol. Biosci., 9, 336 (2009)

[14] Yang D, Liu X, Jiang X, Liu Y, Ying W, Wang H, Bai H, Taylor WD, Wang Y, Clamme JP, Co E, Chivukula P, Tsang KY, Jin Y, Yu L, J. Control. Release, 161, 124 (2012)

[15] Jun YJ, Min JH, Ji DE, Yoo JH, Kim JH, Lee HJ, Jeong B, Sohn YS, Bioorg. Med. Chem. Lett., 18, 6410 (2008)

[16] Kalaria D, Sharma G, Beniwal V, Kumar MR, Pharm. Res., 26, 492 (2009)

[17] Lee E, Lee J, Lee IH, Yu M, Kim H, Chae SY, Jon S, J. Med. Chem., 51, 6442 (2008)

[18] Milas L, Mason KA, Hunter N, Li C, Wallace S, Int. J. Radiat. Oncol., 55, 707 (2003)

[19] Lee E, Kim H, Lee IH, Jon S, J. Control. Release, 140, 79 (2009)

[20] Zhang X, Li Y, Chen X, Wang X, Xu X, Liang Q, Hu J, Jing X, Biomaterials, 26, 2121 (2005)

[21] Li C, Newman RA, Wu QP, Ke S, Chen W, Hutto T, Kan ZX, Brannan MD, Charnsangavej C, Wallace S, Cancer Chemother. Pharmacol., 46, 416 (2000)

[22] Jain AK, Swarnakar NK, Godugu C, Singh RP, Jain S, Biomaterials, 32, 503 (2011)

[23] Schante CE, Zuber G, Herlin C, Vandamme TF, Carbohydr. Polym., 85, 469 (2011)

[24] De Stefano I, Battaglia A, Zannoni GF, Prisco MG, Fattorossi A, Travaglia D, Baroni S, Renier D, Scambia G, Ferlini C, Gallo D, Cancer Chemother. Pharmacol., 68, 107 (2011)

[25] Ogino S, Nishida N, Umemoto R, Suzuki M, Takeda M, Terasawa H, Kitayama J, Matsumoto M, Hayasaka H, Miyasaka M, Shimada I, Structure, 18, 649 (2010)

[26] Manju S, Sreenivasan K, J. Colloid Interface Sci., 359(1), 318 (2011)

[27] Klostergaard J, Auzenne E, Ghosh SC, Khodadadian M, Rivera B, Farquhar D, Price RE, Ravoori M, Kundra V, Freedman RS, Mol. Cancer Ther., 6, 3619S (2007)

[28] Cho HJ, Yoon IS, Yoon HY, Koo H, Jin YJ, Ko SH, Shim JS, Kim K, Kwon IC, Kim DD, Biomaterials, 33, 1190 (2012)

[29] Jiang T, Zhang Z, Zhang Y, Lv H, Zhou J, Li C, Hou L, Zhang Q, Biomaterials, 33, 9246 (2012)

[30] Paliwal R, Paliwal SR, Agrawal GP, Vyas SP, Int. J. Pharm., 422, 179 (2012)

[31] Ke W, Zhao Y, Huang R, Jiang C, Pei Y, J. Pharm. Sci., 97, 2208 (2008)

[32] Hamman JH, Mar. Drugs, 8, 1305 (2010)

[33] Sarmento B, Ribeiro A, Veiga F, Sampaio P, Neufeld R, Ferreira D, Pharm. Res., 24, 2198 (2007)

[34] Yoon H, Kim GH, Macromol. Res., 20(4), 402 (2012)

[35] Smith JM, Dornish M, Wood EJ, Biomaterials, 26, 3269 (2005)

[36] Evans DF, Pye G, Bramley R, Clark AG, Dyson TJ, Hardcastle JD, Gut, 29, 1035 (1988)

[37] Thouzeau C, Peters G, Le Bohec C, Le Maho Y, J. Expe. Biol., 207, 2715 (2004)

[38] Tsao CT, Chang CH, Lin YY, Wu MF, Wang JL, Han JL, Hsieh KH, Carbohydr. Res., 345, 1774 (2010)

[39] Chun C, Lee SM, Kim SY, Yang HK, Song SC, Biomaterials, 30, 2349 (2009)

[40] Feng X, Yuan YJ, Wu JC, Bioorg. Med. Chem. Lett., 12, 3301 (2002)