Article
  • Injectable Thermogel/Microsphere Hybrid Formulation System for Intratympanic Delivery of Dexamethasone

  • Ji Hyun Park# , Geonho Kim*,#, Thi Phuc Le, Da Hae Kim, Eunyoung Seol*,† , and Kang Moo Huh†

  • Department of Polymer Science and Engineering, Chungnam National University, Daejeon 34134, Korea
    *G2GBIO, Inc., Daejeon 34054, Korea

  • 덱사메타손의 고막 내 전달을 위한 주입형 써모젤/미립구 하이브리드 제형 시스템의 제조 및 약물방출 특성 평가

  • 박지현# · 김건호*,# · 레티푹 · 김다해 · 설은영*,† · 허강무†

  • 충남대학교 고분자공학과, *㈜지투지바이오

  • Reproduction, stored in a retrieval system, or transmitted in any form of any part of this publication is permitted only by written permission from the Polymer Society of Korea.

References
  • 1. Hao, J.; Li, S. K. Inner Ear Drug Delivery: Recent Advances, Challenges, and Perspective. Eur. J. Pharm. Sci. 2019, 126, 82-92.
  •  
  • 2. Paulson, D. P.; Abuzeid, W.; Jiang, H.; Oe, T.; O’Malley, B. W.; Li, D. A Novel Controlled Local Drug Delivery System for Inner Ear Disease. Laryngoscope 2008, 118, 706-711.
  •  
  • 3. Pararas, E. E.; Borkholder, D. A.; Borenstein, J. T. Current Strategies for Drug Delivery to the Inner Ear. Acta Pharm. Sin. B 2012, 3, 86-96.
  •  
  • 4. Salt, A. N.; Plontke, S. K. R. Local Inner-ear Drug Delivery and Pharmacokinetics. Drug Discov. Today 2005, 10, 1299-1306.
  •  
  • 5. Kechai, N. E.; Agnely, F.; Mamelle, E.; Nguyen, Y.; Ferrary, E.; Bochot, A. Recent Advances in Local Drug Delivery to the Inner Ear. Bochot, Int. J. Pharm. 2015, 494, 83-101.
  •  
  • 6. Creber, N. J.; Eastwood, H. T.; Hampson, A. J.; Tan, Justin.; O’Leary, S. J. Adjuvant Agents Enhance Round Window Membrane Permeability to Dexamethasone and Modulate Basal to Apical Cochlear Gradients. Eur. J. Pharm. Sci. 2019, 126, 69-81.
  •  
  • 7. McCall, A. A.; Swan, E. E.; Borenstein, J. T.; Sewell, W. F.; Kujawa, S. G.; McKenna, M. J. Drug Delivery for Treatment of Inner Ear Disease: Current State of Knowledge. Ear Hear. 2010, 31, 156-165.
  •  
  • 8. Szeto, B.; Chiang, H.; Valentini, C.; Yu, M.; Kysar, J. W.; Lalwani, A. K. Inner Ear Delivery: Challenges and Opportunities. Laryngoscope Investigative Otolaryngology 2020, 5, 122-131.
  •  
  • 9. Patel, J.; Szczupak, M.; Rajguru, S.; Balaban, C.; Hoffer, M. E. Inner Ear Therapeutics: An Overview of Middle Ear Delivery. Front. Comput. Neurosci. 2019, 13, 261.
  •  
  • 10. Sreenivas, S. A.; Pai, K. V. Thiolated Chitosans: Novel Polymers for Mucoadhesive Drug Delivery – A Review. Trop. J. Pharm. Res. 2008, 7, 1077-1088.
  •  
  • 11. Mader, K.; Lehner, E.; Liebau, A.; Plontke, S. K. Controlled Drug Release to the Inner Ear: Concepts, Materials, Mechanisms, and Performance. Hear. Res. 2018, 368, 49-66.
  •  
  • 12. Schuetz, Y. B.; Gurny, R.; Jordan, O. A Novel Thermoresponsive Hydrogel Based on Chitosan. Eur. J. Pharm. Biopharm. 2008, 68, 19-25.
  •  
  • 13. Sun, K.; Raghavan, S. R. Thermogelling Aqueous Fluids Containing Low Concentrations of Pluronic F127 and Laponite Nanoparticles. Langmuir 2010, 26, 8015-8020.
  •  
  • 14. Jeong, B.; Kim, S. W.; Bae, Y. H. Thermosensitive Sol-gel Reversible Hydrogels. Adv. Drug Deliv. Rev. 2012, 64, 154-162.
  •  
  • 15. Dethe, M. R.; A, P.; Ahmed, H.; Agrawal, M.; Roy, U.; Alexander, A. PCL-PEG Copolymer Based Injectable Thermosensitive Hydrogels. J. Control. Release 2022, 343, 217-236.
  •  
  • 16. Park, S. G.; Li, M. X.; Eom, J. H.; Suh, E. Y.; Cho, W. K.; Joung, Y. K.; Huh, K, M. Synthesis and Charaterization of Gallic Acid Conjugated Glycol Chitosans for Tissue Adhesive Applications. Polym. Korea 2021, 45, 372-379.
  •  
  • 17. Lee, K. Y.; Ha, W. S.; Park, W. H. Blood Compatibility and Biodegradability of Partially N-acylated Chitosan Derivatives. Biomaterials 1995, 16, 1211-1216.
  •  
  • 18. Cho, I. S.; Oh, H. M.; Cho, M. O.; Jang, B. S.; Cho, J. K.; Park, K. H.; Kang, S. W.; Huh, K. M. Synthesis and Characterization of Thiolated Hexanoyl Glycol Chitosan as a Mucoadhesive Thermogelling Polymer. Biomater. Res. 2018, 22, 30.
  •  
  • 19. Yang, Y.; Kim, D. H.; Suh, E. Y.; Kwon, H. C.; Le, T. P.; Kim, Y.; Shin, S. A.; Park, Y. H.; Huh, K. M. Injectable Glycol Chitosan Thermogel Formulation for Efficient Inner Ear Drug Delivery. Carbohydr. Polym. 2022, 278, 118969.
  •  
  • 20. Hoare, T. R.; Kohane, D. S. Hydrogels in Drug Delivery: Progress and Challenges. Polymer 2008, 49, 1993-2007.
  •  
  • 21. Li, J.; Mooney, D. J. Designing Hydrogels for Controlled Drug Delivery. Nat. Rev. Mater. 2016, 1, 16071.
  •  
  • 22. Dang, Q.; Liu, C.; Wang, Y.; Yan, J.; Wan, H.; Fan, B. Characterization and Biocompatibility of Injectable Microspheres-loaded Hydrogel for Methotrexate Delivery. Carbohydr. Polym. 2016, 136, 516-526.
  •  
  • 23. Zheng, Y.; Cheng, Y.; Chen, J.; Ding, J.; Li, M.; Li, C.; Wang, J. C.; Chen, X. Injectable Hydrogel-Microsphere Construct with Sequential Degradation for Locally Synergistic Chemotherapy. ACS Appl. Mater. Interfaces 2017, 9, 3487-3496.
  •  
  • 24. Yang, J. PLGA Microsphere/P(NIPAAm-co-AAm) Hydrogel Combination Systems for Drug Delivery. IOP Conf. Ser.: Mater. Sci. Eng. 2019, 504, 012013.
  •  
  • 25. Ghitman, J.; Biru, E. I.; Stan, R.; Iovu, H. Review of Hybrid PLGA Nanoparticles: Future of Smart Drug Delivery and Theranostics Medicine. Mater. Des. 2020, 193, 108805.
  •  
  • 26. Zhang, W.; Ning, C.; Xu, W.; Hu, H.; Li, M.; Zhao, G.; Ding, J.; Chen, X. Precision-guided Long-acting Analgesia by Gel-immobilized Bupivacaine-loaded Microsphere. Theranostics 2018, 8, 3331-3347.
  •  
  • 27. Lee, E. J.; Kang, E.; Kang, S. W.; Huh, K. M. Thermo-irreversible Glycol Chitosan/hyaluronic Acid Blend Hydrogel for Injectable Tissue Engineering. Carbohydr. Polym. 2020, 244, 116432.
  •  
  • 28. Kim, D. E.; Oh, H. M.; Kang, S. W.; Huh, K. M. Preparation and Characterization of Acyl Glycol Chitosan-Containing Poloxamer Gels. Polym. Korea 2017, 6, 1033-1040.
  •  
  • 29. You, H. S.; Cho, M. O.; Cho, I. S.; Li, Z.; Kim, N. H.; Jang, M. K.; Kang, S. W.; Huh, K. M. Synthesis of N-Acetylated Glycol Chitosans and Their Thermo-sensitive Sol-Gel Transition Properties. Polym. Korea 2016, 40, 328-335.
  •  
  • Polymer(Korea) 폴리머
  • Frequency : Bimonthly(odd)
    ISSN 0379-153X(Print)
    ISSN 2234-8077(Online)
    Abbr. Polym. Korea
  • 2023 Impact Factor : 0.4
  • Indexed in SCIE

This Article

  • 2023; 47(1): 16-25

    Published online Jan 25, 2023

  • 10.7317/pk.2023.47.1.16
  • Received on Aug 13, 2022
  • Revised on Oct 23, 2022
  • Accepted on Oct 27, 2022

Correspondence to

  • Eunyoung Seol* , and Kang Moo Huh

  • Department of Polymer Science and Engineering, Chungnam National University, Daejeon 34134, Korea
    *G2GBIO, Inc., Daejeon 34054, Korea

  • E-mail: eunyoung.seol@g2gbio.com, khuh@cnu.ac.kr