Alendronate-modified hydroxyapatite nanoparticles for bone-specific dual delivery of drug and bone mineral

Seok-Joon Hwang; Ji-Seon Lee; Tae-Kyung Ryu; Rae-Hyung Kang; Ki-Young Jeong; Dae-Ryong Jun; Jung-Min Koh; Sung-Eun Kim; Sung-Wook Choi

Macromolecular Research, Vol.24, No.7, 623-628, July, 2016

DOI10.1007/s13233-016-4094-5 Export Citation

Alendronate-modified hydroxyapatite nanoparticles for bone-specific dual delivery of drug and bone mineral

Seok-Joon Hwang, Ji-Seon Lee, Tae-Kyung Ryu, Rae-Hyung Kang, Ki-Young Jeong, Dae-Ryong Jun, Jung-Min Koh¹, Sung-Eun Kim^{2, †}, and Sung-Wook Choi^†

Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro Wonmi-gu, Bucheon-si, Gyeonggi, 14662, Korea
¹Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Korea
²Department of Orthopaedic Surgery and Rare Diseases Institute, Korea University, Medical College, Guro Hospital, Guro-dong, Guro-gu, Seoul, 08308, Korea

E-mail:,

Alendronate (Alen)-modified hydroxyapatite (HAp) nanoparticles with multilayers of poly(allylamine) (PAA) and alginate (ALG) were fabricated for bone-specific dual delivery of drug and mineral. Negatively charged HAp nanoparticles were coated with three layers of PAA and ALG using a layer-by-layer (LbL) method and then conjugated with Alen at the outmost layer of the LbL-coated HAp nanoparticles via carbodiimide chemistry. Alen-modified HAp nanoparticles had a spherical morphology and an average size of 61.5 nm. The superior adsorption property of the Alen-modified HAp nanoparticles was quantitatively confirmed using tricalcium phosphate disks as a bone model, compared to HAp nanoparticles. Cell culture assays revealed a higher proliferation rate and alkaline phosphatase activity of osteoblasts treated with the Alen-modified HAp nanoparticles.

Keywords:alendronate;hydroxyapatite;layer-by-layer method;dual targeted delivery

[References]

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[Referenced By]

[1] Gass M, Dawson-Hughes B, Am. J. Med., 119, S3 (2006)

[2] Im GI, Qureshi SA, Kenney J, Rubash HE, Shanbhag AS, Biomaterials, 25, 4105 (2004)

[3] Papapoulos SE, Ann. N. Y. Acad. Sci., 1218, 15 (2011)

[4] Silverman SL, Ann. N. Y. Acad. Sci., 1218, 33 (2011)

[5] Rupel K, Perinetti G, Contardo L, Ottaviani G, Gobbo M, De Iudicibus S, Di Lenard R, Biasotto M, J. Mol. Biomarker. Diagn., 5, 1 (2014)

[6] Francis MD, Russell RG, Fleisch H, Science, 165, 1264 (1969)

[7] Leu CT, Luegmayr E, Freedman LP, Rodan GA, Reszka AA, Bone, 38, 628 (2006)

[8] Fleisch H, Graham R, Russell G, Francis MD, Science, 165, 1262 (1969)

[9] Fleisch H, Endocr. Rev., 19, 80 (1998)

[10] Lezcano V, Bellido T, Plotkin LI, Boland R, Morelli S, Arch. Biochem. Biophys., 518, 95 (2012)

[11] Komatsu K, Shimada A, Shibata T, Wada S, Ideno H, Nakashima K, Amizuka N, Noda M, Nifuji A, J. Endocrinol., 219, 145 (2013)

[12] Choi SW, Kim JH, J. Control. Release, 122, 24 (2007)

[13] Wang D, Miller SC, Kopeckova P, Kopecek J, Adv. Drug Deliv. Rev., 57, 1049 (2005)

[14] Wang D, Sima M, Mosley RL, Davda JP, Tietze N, Miller SC, Gwilt PR, Kopeckova P, Kopecek J, Mol. Pharm., 3, 717 (2006)

[15] Pan H, Kopeckova P, Liu J, Wang D, Miller SC, Kopecek J, Pharm. Res., 24, 2270 (2007)

[16] Xie M, Olderoy MO, Zhang Z, Andreassen JP, Strandd BL, Sikorski P, RSC Adv., 2, 1457 (2012)

[17] Jiang SD, Yao QZ, Zhou GT, Fu SQ, J. Phys. Chem., 116, 4484 (2012)

[18] Han J, Zhou ZY, Yin RX, Yang DZ, Nie J, Int. J. Biol. Macromol., 46, 199 (2010)

[19] Watanabea K, Nishiob Y, Makiurac R, Nakahirab A, Kojimac C, Int. J. Pharm., 446, 81 (2013)

[20] Mizushima Y, Ikoma T, Tanaka J, Hoshi K, Ishihara T, Ogawa Y, Ueno A, J. Control. Release, 110, 260 (2006)

[21] Yang YH, Liu CH, Liang YH, Lin FH, Wu KCW, J. Mater. Chem. B, 1, 2447 (2013)

[22] Liang YH, Liu CH, Liao SH, Lin YY, Tang HW, Liu SY, Lai IR, Wu KCW, ACS Appl. Mater. Interfaces, 4, 6720 (2012)

[23] Yadav KS, Chuttani K, Mishra AK, Sawant KK, PDA J. Pharm. Sci. Technol., 65, 131 (2011)

[24] Tang M, Russell PJ, Khatri A, Discov. Med., 7, 68 (2009)

[25] Deligianni DD, Katsala ND, Koutsoukos PG, Missirlis YF, Biomaterials, 22, 87 (2000)

[26] Lampin M, Warocquier-Clerout R, Legris C, Degrange M, Sigot-Luizard MF, J. Biomed. Mater. Res., 36, 99 (1997)

[27] Lincks J, Boyan BD, Blanchard CR, Lohmann CH, Liu Y, Cochran DL, Dean DD, Schwartz Z, Biomaterials, 19, 2219 (1998)

[28] Gittens RA, McLachlan T, Olivares-Navarrete R, Cai Y, Berner S, Tannenbaum R, Schwartz Z, Sandhage KH, Boyan BD, Biomaterials, 32, 3395 (2011)

[29] Sun J, Song F, Zhang W, Sexton BE, Windsor LJ, Arch. Oral Biol., 57, 728 (2012)

[30] Gough JE, Notingher I, Hench LL, J. Biomed. Mater. Res. A, 68, 640 (2004)

[31] Puckett S, Pareta R, Webster TJ, Int. J. Nanomedicine, 3, 229 (2008)

[32] Groessner-Schreiber B, Tuan RS, J. Cell Sci., 101, 209 (1992)