Scintigraphic evaluation of therapeutic angiogenesis induced by VEGF-loaded chitosan nanoparticles in a rodent model of hindlimb ischemia

Tai Kyoung Lee; Chang-Moon Lee; Hyosook Hwang; Hwan-Seok Jeong; Phil-Sun Oh; JeongIl Kwon; Suhn Hee Kim; SeokTae Lim; Myung-Hee Sohn; Hwan-Jeong Jeong

Macromolecular Research, Vol.23, No.6, 531-536, June, 2015

DOI10.1007/s13233-015-3075-4 Export Citation

Scintigraphic evaluation of therapeutic angiogenesis induced by VEGF-loaded chitosan nanoparticles in a rodent model of hindlimb ischemia

Tai Kyoung Lee^{1, 2}, Chang-Moon Lee³, Hyosook Hwang^{1, 2}, Hwan-Seok Jeong^{1, 2}, Phil-Sun Oh^{1, 2}, JeongIl Kwon^{1, 2}, Suhn Hee Kim⁴, SeokTae Lim^{1, 2}, Myung-Hee Sohn^{1, 2}, and Hwan-Jeong Jeong^{1, 2, †}

¹Department of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Geonji-ro 20, Jeonbuk, 560-712, Korea
²Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Geonji-ro 20, Jeonbuk, 560-712, Korea
³Department of Biomedical Engineering, Chonnam National University, Daehak-ro 50, Jeonnam, 550-749, Korea
⁴Department of Physiology, Chonbuk National University Medical School, Geonji-ro 20, Jeonbuk, 560-712, Korea

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We examined the therapeutic effect of chitosan nanoparticles (CHI) incorporating vascular endothelial growth factor (VEGF) on hindlimb ischemia using single photon emission computed tomography (SPECT) perfusion imaging. Rats (n=24) were divided randomly into four groups of six: control, VEGF, CHI, and CHI incorporated with VEGF (CHI-VEGF). The right femoral artery was ligated to block blood flow, and SPECT perfusion images were obtained every week for 4 weeks. The morphology of the synthesized CHI was identified as a spherical shape with an even size distribution (range, 93?250 nm). The VEGF loading efficiency in CHI was 8.6±2.1%. Upon injection into the femoral artery, 17.6±8.2% of the 99mTc-labeled CHI-VEGF administered remained in the ischemic lesion. The restoration of blood flow (ratio of ischemia to normal) measured by SPECT perfusion imaging was greater in animals treated with CHI-VEGF compared to that in the control (p=0.028), VEGF (p=0.010), and CHI (p=0.011) groups. Administering CHI-VEGF had a significant therapeutic effect in a hindlimb ischemic rat model. 99mTc gamma perfusion imaging was useful to study therapeutic angiogenesis.

Keywords:chitosan nanoparticles;vascular endothelial growth factor (VEGF);therapeutic angiogenesis;biomaterials;drug delivery;molecular imaging

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[2] Ouriel K, Shortell CK, DeWeese JA, Green RM, Francis CW, Azodo MV, Gutierrez OH, Manzione JV, Cox C, Marder VJ, J. Vasc. Surg., 19, 1021 (1994)

[3] Ruef J, Hofmann M, Haase J, J. Interv. Cardiol., 17, 427 (2004)

[4] Sabti HA, J. Cardiothorac. Surg., 2, 49 (2007)

[5] Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P, Cardiovasc. Diabetol., 8, 49 (2009)

[6] Wahlberg E, J. Vasc. Surg., 38, 198 (2003)

[7] Mikroulis D, Papanas N, Maltezos E, Bougioukas G, Curr. Vasc. Pharmacol., 5, 195 (2007)

[8] Biscetti F, Straface G, Arena V, Stigliano E, Pecorini G, Rizzo P, Cardiovasc. Diabetol., 8, 49 (2009)

[9] Ahn SH, Min SI, Kin SY, Min SK, Yang HK, Kim SJ, Ha J, J. Korean Surg. Soc., 79, 294 (2010)

[10] Nagpal K, Singh SK, Mishra DN, Chem. Pharm. Bull., 58, 1423 (2010)

[11] Lee CM, Kwon JI, Lee TK, Lim ST, Sohn MH, Jeong HJ, ACS Macro Lett., 3, 1126 (2014)

[12] Giri TK, Thakur A, Ajazuddin AA, Badwaik H, Tripathi DK, Acta Pharmacol. Sin. B, 2, 439 (2012)

[13] Bhattarai N, Gunn J, Zhang M, Adv. Drug Deliv. Rev., 62, 83 (2010)

[14] Ding Y, Shen SZ, Sun H, Sun K, Liu F, Qi Y, Yan J, Mater. Sci. Eng. C-Biomimetic Supramol. Syst., 48, 487 (2015)

[15] Zhou HY, Jiang LJ, Cao PP, Li JB, Chen XG, Carbohydr. Polym., 117, 524 (2015)

[16] Wang JJ, Zeng ZW, Xiao RZ, Xie T, Zhou GL, Zhan XR, Wang SL, Int. J. Nanomedicine, 6, 765 (2011)

[17] Darras V, Nelea M, Winnik FM, Buschmann MD, Carbohydr. Polym., 80, 1137 (2010)

[18] Jonassen H, Kjoniksen AL, Hiorth M, Biomacromolecules, 13(11), 3747 (2012)

[19] Nasti A, Zaki NM, de Leonardis P, Ungphaiboon S, Sansongsak P, Rimoli MG, Tirelli N, Pharm. Res., 26, 1918 (2009)

[20] Bae YH, Park K, J. Control. Release, 153, 198 (2011)

[21] Kim J, Cao L, Shvartsman D, Silva EA, Mooney DJ, Nano Lett., 11, 694 (2011)

[22] Hwang H, Kwon J, Oh PS, Lee TK, Na KS, Lee CM, Jeong HS, Lim ST, Sohn MH, Jeong HJ, Radiology, 273, 160 (2014)

[23] Dokun AO, Keum S, Hazarika S, Li Y, Lamonte GM, Wheeler F, Marchuk DA, Annex BH, Circulation, 117, 1207 (2008)

[24] Kang N, Hai Y, Liang F, Gao CJ, Liu XH, Mol. Med. Rep., 9, 2124 (2014)

[25] Brenes RA, Jadlowiec CC, Bear M, Hashim P, Protack CD, Li X, J. Vasc. Surg., 56, 1669 (2012)

[26] Wang CY, Wen MS, Wang HW, Hsieh IC, Li Y, Liu PY, Circulation, 118, 2166 (2008)

[27] Hershey JC, Baskin EP, Corcoran HA, Bett A, Dougherty NM, Gilberto DB, Mao X, Thomas KA, Cook JJ, Heart Vessels, 18, 142 (2003)

[28] Duan J, Murohara T, Ikeda H, Katoh A, Shintani S, Sasaki K, Kawata H, Yamamoto N, Imaizumi T, Circulation, 102, 370 (2000)

[29] Iskandrian A, Hage F, Shaw L, Mahmarian J, Berman D, JACC Cardiovasc. Imaging, 7, 79 (2014)

[30] Bahk YW, Nucl. Med. Mol. Imaging, 44, 1 (2010)

[31] Zhu A, Shim HS, Nucl. Med. Mol. Imaging, 45, 1 (2011)