Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of Poly (lactide)-b-Poly (glycerol) (PLA-b-PG) Block Copolymer

Poly (lactide)-b-Poly (glycerol) 블록 공중합체의 중합

  • Received : 2017.05.29
  • Accepted : 2017.06.30
  • Published : 2017.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

This study reports a synthesis of an amphiphilic linear block copolymer consisting of a hydrophobic poly (lactide) (PLA) block and a hydrophilic hyperbranched polyglycerol (hbPG) block, PLA-b-hbPG. Simple chemical modification of the hbPG block with 4-hydroxycinnamic acid (CA) led to a photo-crosslinkable block copolymer, PLA-b-hbPG-CA. Nanosized micelles of the block copolyemrs were used as drug carriers for sustainable release. The hbPG shell made of a small molecular weight hbPG block showed excellent hydrophilicity, which can minimize in vivo toxicity. The UV-crosslinked PLA-b-hbPG-CA micelles loaded with drugs colud be served as a drug delivery carrier for its biocompatibility and self-assembled structures.

이 연구는 소수성 폴리락타이드(PLA) 블록과 친수성 하이퍼브랜치드 폴리글리세롤(hbPG) 블록으로 구성된 양친매성 블록 공중합체(PLA-b-hbPG)의 합성방법에 대한 것이다. 또한, hbPG 블록을 4-hydroxyl cinnamic acid (CA)로 에스터 반응화하여, 광가교가 가능한 블록 공중합체인 PLA-b-hbPG-CA에 대한 접근법에 대해서도 보고하였다. 연구된 양친성 고분자는 친수기에 많은 양으로 존재하는 폴리글리세롤에 의해 화장품용 약물 전달체로 사용이 가능한 작은 크기(100 nm)의 마이셀을 형성함을 확인하였다. 또한, hbPG으로 구성된 마이셀의 corona 부분은 우수한 친수성을 나타내어 생체 내 독성을 최소화할 수 있음을 확인하였다. 소수성 활성성분이 담지된 PLA-b-hbPG-CA 마이셀은 생체적합성 및 자기조립구조에 의해 화장품용 약물 전달체로 활용이 가능할 것으로 기대된다.

Keywords

References

  1. F. Ahmed, R. I. Pakunlu, A. Brannan, F. Bates, T. Minko, and D. E. Discher, Biodegradable polymersomes loaded with both paclitaxel and doxorubicin permeate and shrink tumors, inducing apoptosis in proportion to accumulated drug, J. Control. Release, 116, 150 (2006). https://doi.org/10.1016/j.jconrel.2006.07.012
  2. J. Khandare, M. Calderón, N. Dagia, and R. Haag, Multifunctional dendritic polymers in nanomedicine: opportunities and challenges, Chem. Soc. Rev., 41, 2824 (2012). https://doi.org/10.1039/C1CS15242D
  3. A. V. Kabanov and S. V. Vinogradov, Nanogels as pharmaceutical carriers: finite networks of infinite capabilities, Angew. Chem. Int. Ed., 48, 5418 (2009). https://doi.org/10.1002/anie.200900441
  4. F. Yhaya, J. Lim, Y. Kim, M. Liang, A. M. Gregory, and M. H. Stenzel, Development of micellar novel drug carrier utilizing temperature-sensitive block copolymers containing cyclodextrin moieties, Macromolecules, 44, 8433 (2011). https://doi.org/10.1021/ma2013964
  5. J. P. Jain and N. Kumar, Self-assembly of amphiphilic (PEG) 3-PLA copolymer as polymersomes: preparation, characterization, and their evaluation as drug carrier, Biomacromolecules, 11, 1027 (2010). https://doi.org/10.1021/bm1000026
  6. X. Zhang, K. Achazi, D. Steinhilber, F. Kratz, J. Dernedde, and R. Haag, A facile approach for dual- responsive prodrug nanogels based on dendritic polyglycerols with minimal leaching, J. Control. Release, 174, 209 (2014). https://doi.org/10.1016/j.jconrel.2013.11.005
  7. J. C. Hooton, M. D. Jones, and R. Price, Predicting the behavior of novel sugar carriers for dry powder inhaler formulations via the use of a cohesive-adhesive force balance approach, J. Pharm. Sci., 95, 1288 (2006). https://doi.org/10.1002/jps.20618
  8. S. Lee, K. Saito, H. Lee, M. Lee, Y. Shibasaki, Y. Oishi, and B. Kim, Hyperbranched double hydrophilic block copolymer micelles of poly (ethylene oxide) and polyglycerol for pH-responsive drug delivery, Biomacromolecules, 13, 1190 (2012). https://doi.org/10.1021/bm300151m
  9. A. Zarrabi, M. A. Shokrgozar, M. Vossoughi, and M. Farokhi, In vitro biocompatibility evaluations of hyperbranched polyglycerol hybrid nanostructure as a candidate for nanomedicine applications, J. Mater. Sci. - Mater. Med., 25, 499 (2014). https://doi.org/10.1007/s10856-013-5094-z
  10. M. Hu, M., Chen, M., G. Li, Y. Pang, Y. Wang, J. Wu, F. Qiu, X. Zhu, and J. Sun, Biodegradable hyperbranched polyglycerol with ester linkages for drug delivery, Biomacromolecules, 13, 3552 (2012). https://doi.org/10.1021/bm300966d
  11. D. Steinhilber, M. Witting, X. Zhang, M. Staegemann, F. Paulus, W. Friess, S. Küchler, and R. Haag, Surfactant free preparation of biodegradable dendritic polyglycerol nanogels by inverse nanoprecipitation for encapsulation and release of pharmaceutical biomacromolecules, J. Control. Release, 169, 289 (2013). https://doi.org/10.1016/j.jconrel.2012.12.008
  12. A. Tschiche, A. M. Staedtler, S. Malhotra, H. Bauer, C. Böttcher, C. Sharbati, M. Calderón, M. Koch, T. M. Zollner, A. Barnard, D. K. Smith, R. Einspanier, N. Schmidt, and R. Haag, Polyglycerol-based amphiphilic dendrons as potential siRNA carriers for in vivo applications, J. Mater. Chem. B, 2, 2153 (2014). https://doi.org/10.1039/C3TB21364A
  13. D. Wilms, S. E. Stiriba, and H. Frey, Hyperbranched polyglycerols: from the controlled synthesis of biocompatible polyether polyols to multipurpose applications, Acc. Chem. Res., 43, 129 (2010). https://doi.org/10.1021/ar900158p
  14. K. Kainthana and D. E. Brooks, In vivo biological evaluation of high molecular weight hyperbranched polyglycerols, Biomaterials, 28, 4779 (2007). https://doi.org/10.1016/j.biomaterials.2007.07.046
  15. F. Wurm and H. Frey, Linear-dendritic block copolymers: the state of the art and exciting perspectives, Prog. Polym. Sci., 36, 1 (2011). https://doi.org/10.1016/j.progpolymsci.2010.07.009
  16. Y. Oikawa, S. Lee, D. Kim, D. Kang, B. Kim, K. Saito, S. Sasaki, Y. Oishi, and Y. Shibasaki, One-pot synthesis of linear-hyperbranched amphiphilic block copolymers based on polyglycerol derivatives and their micelles, Biomacromolecules, 14, 2171 (2013). https://doi.org/10.1021/bm400275w
  17. X. Li, H. Wen, H. Dong, W. Xue, G. Pauletti, X. Cai, W. Xia, D. Shi, and Y. Li, Self-assembling nanomicelles of a novel camptothecin prodrug engineered with a redox-responsive release mechanism, Chem. Commun., 47, 8647 (2011). https://doi.org/10.1039/c1cc12495a
  18. W. Chen, P. Zhong, F. Meng, R. Cheng, C. Deng, J. Feijen, and Z. Zhong, Redox and pH-responsive degradable micelles for dually activated intracellular anticancer drug release, J. Control. Release, 169, 171 (2013). https://doi.org/10.1016/j.jconrel.2013.01.001
  19. D. Shi, M. Matsusaki, T. Kaneko, and M. Akashi, Photo-cross-linking and cleavage induced reversible size change of bio-based nanoparticles, Macromolecules, 41, 8167 (2008). https://doi.org/10.1021/ma800648e
  20. Z. G. Gao, A. N. Lukyanov, A. Singhal, and V. P. Torchilin, Diacyllipid-polymer micelles as nanocarriers for poorly soluble anticancer drugs, Nano Lett., 2, 979 (2002). https://doi.org/10.1021/nl025604a
  21. Y. Matsumura and H. Maeda, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs, Cancer Res., 46, 6387 (1986).
  22. B. Kim, J. Bae, and K. Park, Enzymatically in situ shell cross-linked micelles composed of 4-arm PPO-PEO and heparin for controlled dual drug delivery, J. Control. Release, 172, 535 (2013). https://doi.org/10.1016/j.jconrel.2013.05.003
  23. Y. Xu, F. Meng, R. Cheng, and Z. Zhong, Reduction-sensitive reversibly crosslinked biodegradable micelles for triggered release of Doxorubicin, Macromol. Biosci., 9, 1254 (2009). https://doi.org/10.1002/mabi.200900233
  24. W. Yuan, K. Fischer, and K. Schärtl, Photocleavable microcapsules built from photoreactive nanospheres, Langmuir, 21, 9374 (2005). https://doi.org/10.1021/la051491+
  25. A. Fitton, J. Hill, D. E. Jane, and R. Millar, Synthesis of simple oxetanes carrying reactive 2-substituents, Synthesis, 12, 1140 (1987).
  26. A. Dworak, L. Panchev, B. Trzebicka, and W. Walach, Poly (${\alpha}$-t-butoxy-${\omega}$-styrylo-glycidol): a new reactive surfactant, Polym. Bull., 40, 461 (1998). https://doi.org/10.1007/s002890050277
  27. F. Ahmed and D. E. Dische, Self-porating polymersomes of PEG-PLA and PEG-PCL: hydrolysis- triggered controlled release vesicles, J. Control. Release, 96, 37 (2004). https://doi.org/10.1016/j.jconrel.2003.12.021
  28. P. Dimitrova, A. Porjazoskab, C. P. Novakova, M. Cvetkovskab, and C. B. Tsvetanov, Functionalized micelles from new ABC polyglycidol-poly (ethylene oxide)-poly (d, l-lactide) terpolymers, Polymer, 46, 6820 (2005). https://doi.org/10.1016/j.polymer.2005.06.002
  29. F. Wurm, J. Nieberle, and H. Frey, Double-hydrophilic linear-hyperbranched block copolymers based on poly (ethylene oxide) and poly (glycerol), Macromolecules, 41, 1184 (2008). https://doi.org/10.1021/ma702308g
  30. M. Gervais, A. Brocas, G. Cendejas, A. Deffieux, and S. Carlott, Synthesis of linear high molar mass glycidol-based polymers by monomer-activated anionic polymerization, Macromolecules, 43, 1778 (2010). https://doi.org/10.1021/ma902286a
  31. A. Sunder, R. Hanselmann, H. Frey, and R. Mulhaupt, Controlled synthesis of hyperbranched polyglycerols by ring-opening multibranching polymerization, Macromolecules, 32, 4240 (1999). https://doi.org/10.1021/ma990090w
  32. B. Neises and W. Steglich, Simple method for the esterification of carboxylic acids, Angew. Chem. Int. Ed., 17, 522 (1978). https://doi.org/10.1002/anie.197805221
  33. A. Khemis, A. Kaiafa, C. Queille-Roussel, L. Duteil, and J. P. Ortonne, Evaluation of efficacy and safety of rucinol serum in patients with melasma: a randomized controlled trial, Br. J. Dermatol., 156, 997 (2007). https://doi.org/10.1111/j.1365-2133.2007.07814.x
  34. J. Kim, J. Shim, Y. Kim, K. Char, K. Suh, and J. Kim, The design of polymer-based nanocarriers for effective transdermal delivery, Macromol. Biosci., 10, 1171 (2010). https://doi.org/10.1002/mabi.201000097