Sains Malaysiana 45(12)(2016): 1849–1855

http://dx.doi.org/10.17576/jsm-2016-4512-09

 

Sintesis dan Pencirian Poli(etilena glikol) bermetoksi-ko-Poli(β-amino ester) yang Dibentuk daripada Heksilamina Linear dan Siklik Sebagai Misel Polimer

(Synthesis and Characterization of Methoxy Poly(ethylene glycol)-co-poly(β-amino ester)

formed by Linear and Cyclic Hexylamines as Polymeric Micelles)

 

 

JIA-CHYI WONG¹, CHIN-HUA CHIA¹*, SWEE-YEE CHIN², POI-SIM KHIEW³

& SARANI ZAKARIA¹

 

¹Pusat Pengajian Fizik Gunaan, Fakulti Sains dan Teknologi, Universiti Kebangsaan Malaysia

43600 Bangi, Selangor Darul Ehsan, Malaysia

 

²International Medical University (IMU), 57000 Kuala Lumpur, Wilayah Persekutuan

Malaysia

 

³Jabatan Kejuruteraan Kimia, Fakulti Kejuruteraan, Universiti Nottingham Kampus Malaysia

43500 Semenyih, Selangor Darul Ehsan, Malaysia

 

Diserahkan: 4 Mei 2016/Diterima: 8 Ogos 2016

 

ABSTRAK

Poli(etilena glikol) bermetoksi-ko-poli(β-amino ester) (MPEG-PbAE) telah disintesis dengan menggunakan poli(etilena glikol) bermetoksi yang mempunyai kumpulan hujung berfungsi akrilat (MPEG-ac), 1,6-heksanadiol diakrilat, heksilamina linear (A) dan heksilamina siklik (B) sebagai bahan reaktan. Kopolimer MPEG-PbAE A dan B dijangka akan membentuk misel dengan MPEG berfungsi sebagai bahagian luar yang hidrofilik dan PbAE yang mempunyai kumpulan heksil berfungsi sebagai bahagian dalam yang hidrofobik. MPEG-ac selepas diubah suai dan kopolimer MPEG-PbAE A dan B selepas disintesis telah dicirikan. Spektroskopi inframerah transformasi Fourier (FT-IR) dan spektroskopi resonans magnet nukleus jenis proton (1H-NMR) telah mengesahkan pengubahsuaian kumpulan hujung hidroksil di MPEG kepada kumpulan hujung akrilat. Didapati kopolimer A adalah lebih sesuai digunakan sebagai pembawa ubat berdasarkan perbandingan antara kopolimer A daripada heksilamina linear dan kopolimer B daripada heksilamina siklik. Kromatografi penelapan gel (GPC) menunjukkan bahawa nombor-purata berat molekul, Mn kopolimer A adalah 11216 dengan indeks kepoliserakan (PDI) 1.1925. Kepekatan misel kritikal (CMC) kopolimer A dalam larutan akueus pH7.4 adalah 84.6 mg/L. Purata saiz misel yang diperoleh daripada analisis penyerakan cahaya dinamik (DLS) adalah 26.25±0.149 nm.

 

Kata kunci: Heksilamina; misel polimer; poli(etilena glikol) bermetoksi-ko-poli(β-amino ester)

 

 

ABSTRACT

Methoxy poly(ethylene glycol)-co-poly(β-amino ester) (MPEG-PbAE) was synthesized using pre-modified acrylated-end methoxy poly(ethylene glycol) (MPEG-ac), 1,6-hexanediol diacrylate, linear hexylamine (A) and cyclic hexylamine (B) as reactants. The MPEG-PbAE copolymer A and B were expected to form micelles where MPEG acts as the hydrophilic shell and the PbAE with hexyl groups acts as the hydrophobic core. The modified MPEG-ac, synthesized MPEG-PbAE copolymer A and B were then characterized. The Fourier transformed infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance spectroscopy (1H-NMR) confirmed the modification of hydroxyl end group of MPEG to acrylate end group. It was found that the copolymer A is more suitable as drug carrier by the comparison between copolymer A formed by linear hexylamine and copolymer B formed by cyclic hexylamine. Gel permeation chromatography (GPC) showed that the number average molecular weight, Mn of the copolymer A was 11216 with polydispersity index (PDI) 1.1925. The critical micelle concentration (CMC) of copolymer A in aqueous solution at pH7.4 is 84.6 mg/L. The average micellar size that are obtained from dynamic light scattering (DLS) analysis was 26.25±0.149 nm.

 

Keywords: Hexylamine; methoxy poly(ethylene glycol)-co-poly(β-amino ester); polymeric micelles

RUJUKAN

Akinc, A., Lynn, D.M., Anderson, D.G. & Langer, R. 2003. Parallel synthesis and biophysical characterization of a degradable polymer library for gene delivery. Journal of the American Chemical Society 125(18): 5316-5323.

Ayre, A.P., Kadam, V.J., Dand, N.M. & Patel, P.B. 2013. Polymeric micelles as a drug carrier for tumor targeting. Chronicles of Young Scientists 4(2): 94-101.

Bui, Q.N., Li, Y., Jang, M.S., Huynh, D.P., Lee, J.H. & Lee, D.S. 2015. Redox- and pH-sensitive polymeric micelles based on poly(β-Amino Ester)-grafted disulfide methylene oxide poly(ethylene glycol) for anticancer drug delivery. Macromolecules 48(12): 4046-4054.

Cho, H., Lai, T.C., Tomoda, K. & Kwon, G.S. 2014. Polymeric micelles for multi-drug delivery in cancer. AAPS PharmSciTech. 16(1): 10-20.

Gaucher, G., Dufresne, M.H., Sant, V.P., Kang, N., Maysinger, D. & Leroux, J.C. 2005. Block copolymer micelles: Preparation, characterization and application in drug delivery. Journal of Controlled Release: Official Journal of the Controlled Release Society 109(1-3): 169-188.

Hoffman, A.S. & Pun, S.H. 2012. Pegylation of drugs and nanocarriers. In Biomaterials Science. 3rd ed., edited by Ratner, B.D., Hoffman, A.S., Schoen, F.J. & Lemons, J.E. Oxford: Academic Press. p. 1028.

Hwang, S.J., Kim, M.S., Han, J.K., Lee, D.S., Park, H.J. & Kim, J.S. 2007. pH-sensitivity control of PEG-Poly(β-Amino Ester) block copolymer micelle. Macromolecular Research 15(5): 437-442.

Kim, M.S., Hwang, S.J., Han, J.K., Choi, E.K., Park, H.J., Kim, J.S. & Lee, D.S. 2006. pH-responsive PEG-Poly(β-Amino Ester) block copolymer micelles with a sharp transition. Macromolecular Rapid Communications 27(6): 447-451.

Ko, J., Park, K., Kim,Y.S., Kim, M.S., Han, J.K., Kim, K., Park, R.W., Kim, I.S., Song, H.K., Lee, D.S. & Kwon, I.C. 2007. Tumoral acidic extracellular pH targeting of pH-responsive MPEG-Poly(β-Amino Ester) block copolymer micelles for cancer therapy. Journal of Controlled Release 123(2): 109-115.

Kwon, G.S. & Okano, T. 1996. Polymeric micelles as new drug carriers. Advanced Drug Delivery Reviews 21(96): 107-116.

Lavasanifar, A., Samuel, J. & Kwon, G.S. 2002. Poly(Ethylene oxide)-block-poly(L-Amino acid) micelles for drug delivery. Adv. Drug Deliv. Rev. 54(2): 169-190.

Lynn, D.M., Anderson, D.G., Putnam, D. & Langer, R. 2001. Accelerated discovery of synthetic transfection vectors: Parallel synthesis and screening of a degradable polymer library. Journal of the American Chemical Society 123(33): 8155-8156.

Lynn, D.M. & Langer, R. 2000. Degradable poly(Beta-Amino Esters): Synthesis, characterization, and self-assembly with plasmid DNA. J. Am. Chem. Soc. 122(10): 10761-10768.

Min, K.H., Kim, J.H., Bae, S.M., Shin, H., Kim, M.S., Park, S., Lee, H., Park, R.W., Kim, I.S., Kim, K., Kwon, I.C., Jeong, S.Y. & Lee, D.S. 2010. Tumoral acidic pH-responsive MPEG-Poly(β-Amino Ester) polymeric micelles for cancer targeting therapy. Journal of Controlled Release 144(2): 259-266.

Movassaghian, S., Merkel, O.M. & Torchilin, V.P. 2015. Applications of polymer micelles for imaging and drug delivery. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 7(5): 691-707.

Peng, T., Li, Y., Ahn, D., Kim, B.S. & Lee, D.S. 2013. Synthesis and characterization of pH-responsive poly(2-Hydroxyethyl Aspartamide)-G-Poly(β-Amino Ester) graft copolymer micelles as potential drug carriers. Macromolecular Research 21(4): 400-405.

Stuart, B.H. 2004. Infrared Spectroscopy: Fundamentals and Applications. New York: John Wiley & Sons Ltd.

Wu, Xiang Lan, Jong Ho Kim, Heebeom Koo, Sang Mun Bae, Hyeri Shin, Min Sang Kim, Byung Heon Lee, Park, R.W., Kim, I.S., Choi, K., Kwon, I.C., Kim, K. & Lee, D.S. 2010. Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy. Bioconjugate Chemistry 21(2): 208-213.

Zhang, Y., Huang, Y. & Li, S. 2014. Polymeric micelles: Nanocarriers for cancer-targeted drug delivery. AAPS PharmSciTech 15(4): 862-871.

Zhao, H., Duong, H.H. & Yung, L.Y. 2010. Folate-conjugated polymer micelles with pH-triggered drug release properties. Macromolecular Rapid Communications 31(13): 1163-1169.

 

 

*Pengarang untuk surat-menyurat; email: chia@ukm.edu.my