Cell-penetrating peptide-modified PLGA nanoparticles for enhanced nose-to-brain macromolecular delivery

Lu Yan; Huiyuan Wang; Yifan Jiang; Jinhua Liu; Zhao Wang; Yongxin Yang; Shengwu Huang; Yongzhuo Huang

Macromolecular Research, Vol.21, No.4, 435-441, April, 2013

DOI10.1007/s13233-013-1029-2 Export Citation

Cell-penetrating peptide-modified PLGA nanoparticles for enhanced nose-to-brain macromolecular delivery

Lu Yan^{1, 2}, Huiyuan Wang^{1, 3}, Yifan Jiang^{1, 3}, Jinhua Liu^{1, 3}, Zhao Wang^{1, 3}, Yongxin Yang^{1, 3}, Shengwu Huang², and Yongzhuo Huang^{1, 4, †}

¹Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Hai-ke Rd, Shanghai, 201203, P. R. China
²College of Pharmaceutical Sciences, Zhejiang University of TCM, 548 Bing-wen Rd, Hangzhou, 310053, P. R. China
³, China
⁴Ministry of Education & PLA, Key Lab of Smart Drug Delivery (Fudan University), Shanghai, P. R. China

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Macromolecular drugs become an essential part in neuroprotective treatment. However, the nature of ineffective delivery crossing the blood brain barrier (BBB) renders those macromolecules undruggable for clinical practice. Recently, brain target via intranasal delivery have provided a promising solution to circumventing the BBB. Despite the direct route from nose to brain (i.e. olfactory pathway), there still are big challenges for large compounds like proteins to overcome the multiple delivery barriers such as nasal mucosa penetration, intracellular transport along the olfactory neuron, and diffusion across the heterogeneous brain compartments. Herein presented is an intranasal strategy mediated by cell-penetrating peptide modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles for the delivery of insulin to the brain, a potent therapeutic against Alzheimer’s disease. The results revealed that the cell-penetrating peptide can potentially deliver insulin into brain via the nasal route, showing a total brain delivery efficiency of 6%. It could serve as a potential treatment for neurodegenerative diseases.

Keywords:cell-penetrating peptide;intranasal delivery;brain target;insulin;PLGA nanoparticles

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[2] Suman JD, Expert Opin. Biol. Ther., 3, 519 (2003)

[3] Huang Y, Park YS, Wang J, Moon C, Kwon YM, Chung HS, Park YJ, Yang VC, Curr. Pharm. Des., 16, 2369 (2010)

[4] Langel U, Cell-Penetrating Peptides, Springer, New York, 2010.

[5] Liu JH, Zhao YX, Guo QQ, Wang Z, Wang HY, Yang YX, Huang YZ, Biomaterials, 33, 6155 (2012)

[6] Wang YH, Chen CP, Chan MH, Chang M, Hou YW, Chen HH, Hsu HR, Liu K, Lee HJ, Biochem. Biophys. Res. Commun., 346(3), 758 (2006)

[7] Hou YW, Chan MH, Hsu HR, Liu BR, Chen CP, Chen HH, Lee HJ, Experimental Dermatology, 16, 999 (2007).

[8] Cohen E, Dillin A, Nat. Rev. Neurosci., 9, 759 (2008)

[9] Laron Z, Arch. Physiol. Biochem., 115, 112 (2009)

[10] Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B, Arch. Neurol., 69, 29 (2012)

[11] Astete CE, Sabliov CM, J. Biomater. Sci.-Polym. Ed., 17, 247 (2006)

[12] Yang R, Shim WS, Cui FD, Cheng G, Han X, Jin QR, Kim D, Chung SJ, Shim CK, Int. J. Pharm., 371, 142 (2009)

[13] Liang GF, Zhu YL, Sun B, Hu FH, Tian T, Li SC, Xiao ZD, Nanoscale Res. Lett., 6, 447 (2011)

[14] Kim SH, Jeong JH, Chun KW, Park TG, Langmuir, 21(19), 8852 (2005)

[15] Torchilin VP, Adv. Drug Deliv. Rev., 60, 548 (2008)

[16] Ruan G, Agrawal A, Marcus AI, Nie S, J. Am. Chem. Soc., 129(47), 14759 (2007)

[17] Som A, Tezgel AO, Gabriel GJ, Tew GN, Angew. Chem.-Int. Edit., 50, 6147 (2011)

[18] Cai Q, Shi G, Bei J, Wang S, Biomaterials, 24, 629 (2003)

[19] Pan H, Jiang H, Chen W, Biomaterials, 29, 1583 (2008)

[20] Schwarze SR, Ho A, Vocero-Akbani A, Dowdy SF, Science, 285, 1569 (1999)

[21] Dietz GP, Bahr M, Brain Res. Bull., 68, 103 (2005)

[22] He H, David AE, Zhang J, Park YS, Wang J, Huang Y, Wang J, Yang VC, Macromol. Res., 19(12), 1224 (2011)

[23] Liang JF, Yang VC, Biochem. Biophys. Res. Commun., 335(3), 734 (2005)

[24] Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM, J. Control. Release, 125, 193 (2008)

[25] Wen Z, Yan Z, He R, Pang Z, Guo L, Qian Y, Jiang X, Fang L, Drug Deliv., 18, 555 (2011)

[26] Semete B, Booysen L, Lemmer Y, Kalombo L, Katata L, Verschoor J, Swai HS, Nanomedicine, 6, 662 (2010)