 |
 |
 |
 |
 |
 |
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 Received: 4 May 2016/Accepted: 8 August 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 REFERENCES 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. *Corresponding author; email: chia@ukm.edu.my
|
|||
|
