pH-Sensitivity Control of PEG-Poly(β-amino ester) Block Copolymer Micelle

Su Jong Hwang; Min Sang Kim; Jong Kwon Han; Doo Sung Lee; Bong Sup Kim; Eun Kyung Choi; Heon Joo Park; Jin Seok Kim

Macromolecular Research, Vol.15, No.5, 437-442, August, 2007

Su Jong Hwang, Min Sang Kim, Jong Kwon Han, Doo Sung Lee^†, Bong Sup Kim¹, Eun Kyung Choi², Heon Joo Park³, and Jin Seok Kim⁴

Department of Polymer Science & Engineering, Sungkyunkwan University, Suwon 440-746, Korea
¹Polymer Technology Institute, Sungkyunkwan University, Suwon 440-746, Korea
²Department of Radiation Oncology, University of Ulsan, Ulsan 680-749, Korea
³Department of Microbiology, College of Medicine, Inha University, Incheon 402-751, Korea
⁴College of Pharmacy, Sookmyung Women’s University, Seoul 140-732, Korea

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Poly(ethylene glycol) methyl ether (PEG)-poly(β-amino ester) (PAE) block copolymers were synthesized using a Michael-type step polymerization, and the construction of pH-sensitive polymeric micelles (PM) investigated. The β-amino ester block of the block copolymers functioned as a pH-sensitive moiety as well as a hydrophobic block in relation to the ionization of PAE, while PEG acted as a hydrophilic block, regardless of ionization. The synthesized polymers were characterized using 1H-NMR, with their molecular weights measured using gel permeation chromatography. The pKb values of the pH-sensitive polymers were measured using a titration method. The pH-sensitivity and critical micelle concentration (CMC) of the block copolymers in PBS solution were estimated using fluorescence spectroscopy. The pH dependent micellization behaviors with various bisacrylate esters varied within a narrow pH range. The critical micelle concentration at pH 7.4 decreased from 0.032 to 0.004 mg/mL on increasing the number of methyl group in the bisacrylate from 4 to 10. Also, the particle size of the block copolymer micelles was determined using dynamic light scattering (DLS). The DLS results revealed the micelles had an average size below 100 nm. These pH-sensitive polymeric micelles may be good carriers for the delivery of an anticancer drug.

Keywords:block copolymers;pH-sensitive;polymeric micelle;β-amino ester

[References]

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Torres-Lugo M, Peppas NA, Macromolecules, 32(20), 6646 (1999)
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[Referenced By]

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[1] Torchilin VP, J. Control. Release, 73, 137 (2001)

[2] Kwon GS, Kataoka K, Adv. Drug Deliv. Rev., 16, 295 (1995)

[3] Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM, Chem. Rev., 99(11), 3181 (1999)

[4] Annette R, Guido WM, Vandermeulen, HarmAnton K, Adv. Drug Deliv. Rev., 53, 95 (2001)

[5] Yokoyama M, Biorelated polymers and gels, T. Okano, Ed., San Diego, Academic Press, 1998, p. 193

[6] Jones MC, Leroux JC, Eur. J. Pharm. Biopharm., 48, 101 (1999)

[7] Kavanov AV, Chekhonin VP, Alakhov VY, Batrakova EV, Lebedev AS, Melik Nubranov NS, Arzhakov SA, Levashov AV, Morozov GV, Severin Kabanov ES, Kabanov VA, FEBS Lett, 258, 343 (1989)

[8] Ding Z, Long CJ, Hayashi Y, Bulmus EV, Hoffman AS, Stayton PS, Bioconjugate Chem., 10, 395 (1999)

[9] Jeong B, Bae YH, Lee DS, Kim SW, Nature, 338, 860 (1997)

[10] Soppimath KS, Kulkarni AR, Aminabhavi TM, J. Control. Release, 75, 331 (2001)

[11] Torres-Lugo M, Peppas NA, Macromolecules, 32(20), 6646 (1999)

[12] Yao L, Krause S, Macromolecules, 36(6), 2055 (2003)

[13] Filipcsei G, Feher J, Zrinyi M, J. Mol. Struct., 554, 109 (2000)

[14] Kang SI, Bae YH, J. Control. Release, 80, 145 (2002)

[15] Taillefer J, Jones MC, Brasseur N, Vanlier JE, Leroux JC, J. Pharm. Sci., 89, 52 (2000)

[16] Tonge SR, Tighe BJ, Adv. Drug Deliv. Rev., 53, 109 (2001)

[17] Murthy N, Robichaud JR, Tirrell DA, Stayton PS, Hoffman AS, J. Control. Release, 61, 137 (1999)

[18] Lee AS, Butun V, Vamvakaki M, Armes SP, Pople JA, Gast AP, Macromolecules, 35(22), 8540 (2002)

[19] Gohy JF, Lohmeijer BGG, Varshney SK, Decamps B, Leroy E, Boileau S, Schubert US, Macromolecules, 35(26), 9748 (2002)

[20] Kim MS, Hwang SJ, Han JK, Choi EK, Park HJ, Kim JS, Lee DS, Macromol. Rapid Commun., 27, 447 (2006)

[21] Bae YS, Jang WD, Nishiyama N, Fukushima S, Kataoka K, Mol. Biosyst., 1, 242 (2005)

[22] Kim MS, Lee DS, Choi EK, Park HJ, Kim JS, Macromol. Res., 13(2), 147 (2005)

[23] Pal RR, Lee DS, Macromol. Res., 13(5), 373 (2005)