화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Journal of Industrial and Engineering Chemistry, Vol.90, 36-46, October, 2020
DOI10.1016/j.jiec.2020.06.004  Export Citation
Fabrication of pH responsive coacervates using a polycation-b-polypropylene glycol diblock copolymer for versatile delivery platforms
Mani Gajendiran, Sungjun Kim, Heejung Jo1, and Kyobum Kim†
  • Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
  • 1Department of Bioengineering, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Republic of Korea
E-mail:
A new poly (3-arginylamino propylene succinate-b-polypropylene glycol) (PAPS-PPG) diblock copolymer was synthesized by one-pot ring opening polymerization (ROP) technique. 1H NMR spectral technique was used to determine arginine conjugation efficiency and molecular weight of final polycations by using 4,4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA) as an internal standard. The PAAPS-PPG polycation was electrostatically complexed with heparin (HEP) at an isoelectric point to obtain PAAPS-PPG/HEP coacervate microparticles (Coa MPs). The PAAPS-PPG/HEP Coa MPs exhibit acid induced dissociation at pH 5, but PAAPS/HEP Coa MPs without PPG block do not show acid induced dissociation. The PPG block in PAAPS-PPG/HEP Coa MPs increased 20 folds of cell attachment efficiency on human mesenchymal stem cells (hMSCs). The PAAPS-PPG/HEP Coa MPs could effectively encapsulate siRNA and exhibit more than 95% cell viability up to 200 μg/mL. Hence, the pH responsive PAAPS-PPG/HEP Coa MPs platform with enhanced stem cell attachment ability would find potential application in gene delivery.
Keywords:One-pot polymerization;Cationic block copolymer;pH responsive coacervates;Stem cell affinity;siRNA encapsulation
  1. Cui PF, Qi LY, Wang Y, Yu RY, He YJ, Xing L, Jiang HL, J. Control. Release, 303, 253 (2019)
  2. Chen YJ, Diaz-Dussan D, Peng YY, Narain R, Biomacromolecules, 20(5), 2068 (2019)
  3. Park U, Lee MS, Jeon J, Lee S, Hwang MP, Wang Y, Yang HS, Kim K, Acta Biomater., 90, 179 (2019)
  4. Kim K, Chen WCW, Heo Y, Wnag Y, Prog. Polym. Sci., 60, 18 (2016)
  5. Kaibara K, Okazaki T, Bohidar HB, Dubin PL, Biomacromolecules, 1(1), 100 (2000)
  6. Salehi A, Desai PS, Li JY, Steele CA, Larson RG, Macromolecules, 48(2), 400 (2015)
  7. McTigue WCB, Perry SL, Soft Matter, 15, 3089 (2019)
  8. Kim S, Kim J, Gajendiran M, Yoon M, Hwang MP, Wang YD, Kang BJ, Kim K, Biomacromolecules, 19(11), 4239 (2018)
  9. Lee MS, Ahmad T, Lee J, Awada HK, Wang Y, Kim K, Shin H, Yang HS, Biomaterials, 124, 65 (2017)
  10. Chen WCW, Lee BG, Park DW, Kim K, Chu H, Kim K, Huard J, Wang Y, Biomaterials, 72, 138 (2015)
  11. Hwang MP, Fecek RJ, Qin T, Storkus WJ, Wang Y, J. Control. Release, 318, 270 (2020)
  12. Li R, Wu J, Lin Z, Nangle MR, Li Y, Cai P, Liu D, Ye L, Xiao Z, He C, Ye J, Zhang H, Zhao Y, Wang J, Li X, He Y, Ye Q, Xiao J, Exp. Neurol., 288, 1 (2017)
  13. Wu J, Ye JJ, Zhu JJ, Xiao ZC, He CC, Shi HX, Wang YD, Ling C, Zhang HY, Zhao YZ, Fu XB, Chen H, Li XK, Li L, Zheng J, Xiao J, Biomacromolecules, 17(6), 2168 (2016)
  14. Hwang MP, Ding X, Gao J, Acharya AP, Little SR, Wang Y, Soft Matter, 14, 387 (2018)
  15. Werfel TA, Jackson MA, Kavanaugh TE, Kirkbride KC, Miteva M, Giorgio TD, Duvall C, J. Control. Release, 255, 12 (2017)
  16. Frere A, Baroni A, Hendrick E, Delvigne AS, Orange F, Peulen O, et al., ACS Appl. Mater. Interfaces, 9, 2181 (2017)
  17. Jo HJ, Gajendiran M, Kim KB, J. Ind. Eng. Chem., 82, 234 (2020)
  18. Jo H, Gajendiran M, Kim K, Macromol. Biosci., 19, 190020 (2019)
  19. Mishra S, Webster P, Davis ME, Eur. J. Cell Biol., 83, 97 (2004)
  20. Hatakeyama H, Akita H, Harashima H, Biol. Pharm. Bull., 36, 892 (2013)
  21. Sharma D, Singh J, Bioconjug. Chem., 28, 2772 (2017)
  22. Zhang R, Zheng N, Song Z, Yin L, Cheng J, Biomaterials, 35, 3443 (2014)
  23. Liu Z, Zhang Z, Zhou C, Jiao Y, Prog. Polym. Sci, 35, 1144 (2010)
  24. Ju J, Huan ML, Wan N, Qiu H, Zhou SY, Zhang BL, Int. J. Mol. Sci., 16(3), 5666 (2015)
  25. Lv J, Chang H, Wang Y, Wang M, Xiao J, Zhang Q, Cheng Y, J. Mater. Chem. B, 3, 642 (2015)
  26. Brissault B, Kichler A, Guis C, Leborgne C, Danos O, Cheradame H, Bioconjug. Chem., 14, 581 (2003)
  27. Neamnark A, Suwantong O, Hsu RBKCCYM, Supaphol P, Uludag H, Mol. Pharm., 6, 1798 (2009)
  28. Liu Z, Janzen J, Brooks DE, Biomaterials, 31, 3364 (2010)
  29. Lai TC, Kataoka K, Kwon GS, Biomaterials, 32, 4594 (2011)
  30. Chu DSH, Schellinger JG, Shi J, Convertine AJ, Stayton PS, Pun SH, Accounts Chem. Res., 45, 1089 (2012)
  31. Johnson RN, Chu DSH, Shi J, Schellinger JG, Carlson PM, Pun SH, J. Control. Release, 155, 303 (2011)
  32. DiCiccio AM, Coates GW, J. Am. Chem. Soc., 133(28), 10724 (2011)
  33. Nowick JS, Khakshoor O, Hashemzadeh M, Brower JO, Org. Lett., 5, 3511 (2003)
  34. Obermeier B, Wurm F, Frey H, Macromolecules, 43(5), 2244 (2010)
  35. Chu HH, Gao J, Wang YD, Biotechnol. Prog., 28(1), 257 (2012)
  36. Gajendiran M, Jo H, Kim K, Balasubramanian S, Int. J. Nanomed., 14, 819 (2019)
  37. Jalsovszky G, Holly S, Hollosi M, J. Mol. Struct., 348, 329 (1995)
  38. Stewart JE, J. Chem. Phys., 30, 1259 (1959)
  39. Heydari A, Hosseini SE, Adv. Synth. Catal., 347, 1929 (2005)
  40. Gajendiran M, Yousuf SMJ, Elangovan V, Balasubramanian S, J. Mater. Chem. B, 2, 418 (2014)
  41. Johnson NR, Ambe T, Wang Y, Acta Biomater., 10, 40 (2014)
  42. Zhou D, Pierucci L, Gao Y, O’Keeffe Ahern J, Huang X, Sigen A, Wang W, ACS Appl. Mater. Interfaces, 9, 5793 (2017)
  43. Blocher WC, Perry SL, WIREs Nanomed. Nanobiotechnol., 9 (2017)
  44. Black KA, Priftis D, Perry SL, Yip J, Byun WY, Tirrell M, ACS Macro Lett., 3, 1088 (2014)
  45. Fischer D, Bieber T, Li Y, Elsasser HP, Kissel T, Pharm. Res., 16, 1273 (1999)
  46. Wan N, Huan ML, Ma XX, Jing ZW, Zhang YX, Li C, Zhou SY, Zhang BL, Nanotechnology, 28 (2017)
  47. Zhao F, Yin H, Zhang ZX, Li J, Biomacromolecules, 14(2), 476 (2013)
  48. Chen W, Deng W, Xu X, Zhao X, Vo JN, Anwer AG, Williams TC, Cui H, Goldys EM, J. Mater. Chem. B, 6, 5269 (2018)
  49. Wang Y, Li J, Chen Y, Oupicky D, Biomater. Sci., 3, 1114 (2015)
  50. Chou ST, Hom K, Zhang D, Leng Q, Tricoli LJ, Hustedt JM, Lee A, Shapiro MJ, Seog J, Kahn JD, Mixson AJ, Biomaterials, 35, 846 (2014)
  51. Alameh M, Lavertu M, Tran-Khanh N, Chang CY, Lesage F, Bail M, Darras V, Chevrier A, Buschmann MD, Biomacromolecules, 19(1), 112 (2018)
  52. Wang C, Yuan W, Xiao F, Gan Y, Zhao X, Zhai Z, Zhao X, Zhao C, Cui P, Jin T, Chen X, Zhang X, Front. Pharmacol., 8 (2017)
  53. Helmschrodt C, Hobel S, Schoniger S, Bauer A, Bonicelli J, Gringmuth M, Fietz SA, Aigner A, Richter A, Richter F, Mol. Ther. Nucleic Acids, 9, 57 (2017)
  54. Zhou Z, Zhang Q, Zhang M, Li H, Chen G, Qian C, Oupicky D, Sun M, Theranostics, 8, 4604 (2018)