ACS Publications. Most Trusted. Most Cited. Most Read
A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles
My Activity

Figure 1Loading Img
    Article

    A Novel Sustained-Release Formulation of Recombinant Human Growth Hormone and Its Pharmacokinetic, Pharmacodynamic and Safety Profiles
    Click to copy article linkArticle link copied!

    View Author Information
    National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China
    Graduate School of the Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China
    § Department of Laboratory Animal Science, Peking University Health Science Center, Beijing, 100191, People’s Republic of China
    BioTherapeutics R&D, Pfizer Inc., Chesterfield, Missouri 63017, United States
    *No. 1 Bei Er Tiao, Zhongguancun, Haidian District, Beijing 100190, China. Tel/fax: +86 10 82627072. E-mail: [email protected] (Y.W.); [email protected] (G.M.).
    Other Access Options

    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2012, 9, 7, 2039–2048
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp300126t
    Published June 2, 2012
    Copyright © 2012 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    An effective and safe formulation of sustained-release rhGH for two months using poly(monomethoxypolyethylene glycol-co-d,l-lactide) (mPEG-PLA, PELA) microspheres was developed to reduce the frequency of medication. The rhGH-loaded PELA microspheres with a narrow size distribution were successfully prepared by a double emulsion method combined with a premix membrane emulsification technique without any exogenous stabilizing excipients. The narrow size distribution of the microspheres would guarantee repeatable productivity and release behavior. Moreover, the amphiphilic PELA improved the bioactivity retention of protein drugs since it prevented protein contact with the oil/water interface and the hydrophobic network, and modulated diffusion of acidic degradation products from the carrier system. These PELA microspheres were compared in vivo with commercial rhGH solution, conventional poly(d,l-lactic acid) (PLA) and poly(d,l-lactic-co-glycolic acid) (PLGA) microspheres. Administration of rhGH-PELA could extend the duration of rhGH release (for up to 56 days) and increase area under the curve (AUC) compared to rhGH solution, PLA or PLGA microspheres in Sprague–Dawley (SD) rats. In addition, rhGH-PELA microspheres induced a greater response in total insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) than other rhGH formulations. With a hypophysectomized SD rat model, the pharmacological efficacy of rhGH-PELA microspheres was shown to be better than that from daily administration of rhGH solutions over 6 days based on body weight gain and width of the tibial growth plate. Histological examination of the injection sites indicated a significantly milder inflammatory response than that observed after injection of PLA and PLGA microspheres. Neither anti-rhGH antibodies nor the toxic effects on heart, liver and kidney were detectable after administration of rhGH-PELA microspheres in SD rats. These results suggest that rhGH-PELA microspheres have the potential to be clinically effective and safe when administered only once every two months, a dose regimen for better patient acceptance and compliance.

    Copyright © 2012 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai

    This article is cited by 39 publications.

    1. Zejing Gao, Yi Wei, Jia Ge, Jingxuan Liu, Ying Qin, Fangling Gong, Guanghui Ma. Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment. ACS Applied Materials & Interfaces 2024, 16 (20) , 25869-25878. https://doi.org/10.1021/acsami.4c04010
    2. Zahra Lotfi-Sousefi, Faramarz Mehrnejad, Somayeh Khanmohammadi, S. Fatemeh Kaboli. Insight into the Microcosm of the Human Growth Hormone and Its Interactions with Polymers and Copolymers: A Molecular Dynamics Perspective. Langmuir 2021, 37 (1) , 90-104. https://doi.org/10.1021/acs.langmuir.0c02441
    3. Poulomi Polley, Shivam Gupta, Ruby Singh, Arpan Pradhan, Suparna Mercy Basu, Remya V., Sunil Kumar Yadava, Jyotsnendu Giri. Protein–Sugar-Glass Nanoparticle Platform for the Development of Sustained-Release Protein Depots by Overcoming Protein Delivery Challenges. Molecular Pharmaceutics 2020, 17 (1) , 284-300. https://doi.org/10.1021/acs.molpharmaceut.9b01022
    4. Xiao-Fei Xu, Cai-Yuan Pan, Wen-Jian Zhang, Chun-Yan Hong. Polymerization-Induced Self-Assembly Generating Vesicles with Adjustable pH-Responsive Release Performance. Macromolecules 2019, 52 (5) , 1965-1975. https://doi.org/10.1021/acs.macromol.9b00144
    5. Yaohua Gao, Yanyi Xu, Adam Land, Justin Harris, Gina M. Policastro, Erin P. Childers, Todd Ritzman, Joshua Bundy, and Matthew L. Becker . Sustained Release of Recombinant Human Growth Hormone from Bioresorbable Poly(ester urea) Nanofibers. ACS Macro Letters 2017, 6 (8) , 875-880. https://doi.org/10.1021/acsmacrolett.7b00334
    6. Usha Pramod Shinde, Hyo Jung Moon, Du Young Ko, Bo Kyong Jung, and Byeongmoon Jeong . Control of rhGH Release Profile from PEG–PAF Thermogel. Biomacromolecules 2015, 16 (5) , 1461-1469. https://doi.org/10.1021/acs.biomac.5b00325
    7. Ying Qin, Yi Wei, Zejing Gao, Jingxuan Liu, Donglin Sui, Yuning Hu, Fangling Gong, Guanghui Ma. Preparation and in vitro/in vivo evaluation of uniform-sized Goserelin-loaded sustained release microspheres. Journal of Controlled Release 2024, 375 , 745-757. https://doi.org/10.1016/j.jconrel.2024.09.043
    8. Jie Zhou, Shengnan Li, Jin Zhang, Fusui Luo, Yiwen Sun, Min Guan, Huili Ma, Qian Liu. Ionic liquid combined with bile acid pathway for oral delivery of rhGH. Journal of Drug Delivery Science and Technology 2023, 86 , 104664. https://doi.org/10.1016/j.jddst.2023.104664
    9. . Applications of Uniform Particles in Sustained Release of Drugs. 2023, 163-199. https://doi.org/10.1002/9783527830855.ch6
    10. Miusi Shi, Kevin J. McHugh. Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems. Advanced Drug Delivery Reviews 2023, 199 , 114904. https://doi.org/10.1016/j.addr.2023.114904
    11. Jie Zhang, Gongwei Li, Yanping Cao, Duoxia Xu. The Improvement of Dispersion Stability and Bioaccessibility of Calcium Carbonate by Solid/Oil/Water (S/O/W) Emulsion. Foods 2022, 11 (24) , 4044. https://doi.org/10.3390/foods11244044
    12. Seung Ho Lee, Cho Rim Kim, Yong Chan Cho, Se-Na Kim, Byung Hwi Kim, Cheol Lee, Han Bi Ji, Jae Hoon Han, Chun Gwon Park, HyeonJi Hong, Young Bin Choy. Magnetically actuating implantable pump for the on-demand and needle-free administration of human growth hormone. International Journal of Pharmaceutics 2022, 618 , 121664. https://doi.org/10.1016/j.ijpharm.2022.121664
    13. Xibang Zhao, Yuanyuan Zhou, Jianting Li, Chao Zhang, Jiali Wang. Opportunities and challenges of hydrogel microspheres for tendon–bone healing after anterior cruciate ligament reconstruction. Journal of Biomedical Materials Research Part B: Applied Biomaterials 2022, 110 (2) , 289-301. https://doi.org/10.1002/jbm.b.34925
    14. Somayeh Khanmohammadi, Faramarz Mehrnejad, Zahra Lotfi-Sousefi, Mohammad Yahyaei, Hossein Naderi-manesh. Design and synthesis of polyacrylic acid/deoxycholic acid-modified chitosan copolymer and a close inspection of human growth hormone-copolymer interactions: An experimental and computational study. Colloids and Surfaces B: Biointerfaces 2021, 206 , 111956. https://doi.org/10.1016/j.colsurfb.2021.111956
    15. Nianfeng Jiang, Xiangyu Zheng, Yan Feng, Hongtao Wu, Mingwei Yuan, Yi He, Hongli Li, Minglong Yuan. Preparation and in vitro release of total alkaloids from alstonia scholaris leaf-loaded mPEG-PMA microspheres. Materials Research Express 2021, 8 (8) , 085304. https://doi.org/10.1088/2053-1591/ac1cab
    16. Hossein Honari, , Mohammadebrahim Minaei, , Hasan Mirhaj, , Seyyed Masih Etemad- Ayoubi, . Antibody titers of PEG-PLA block copolymer nanosphere containing chimeric recombinant protein of protective antigen and lethal factor of Bacillus anthracis. Koomesh journal 2021, 23 (4) , 441-448. https://doi.org/10.52547/koomesh.23.4.441
    17. Huijuan Jin, Huihui Chong, Yuanmei Zhu, Mengqiu Zhang, Xun Li, Nardana Bazybek, Yi Wei, Fangling Gong, Yuxian He, Guanghui Ma. Preparation and evaluation of amphipathic lipopeptide‐loaded PLGA microspheres as sustained‐release system for AIDS prevention. Engineering in Life Sciences 2020, 20 (11) , 476-484. https://doi.org/10.1002/elsc.202000026
    18. Siyavash Mirzaei, Hamid Mobedi, Hamid Gourabi, Mohammad Hossein Sanati, Sakine Khezli, Hamid Omidian, Sima Sadrai. Release of human growth hormone from an in-situ implant modulated by poly(ethylene glycol) dimethyl ether and tris(hydroxymethyl) aminomethane. Iranian Polymer Journal 2020, 29 (11) , 1019-1029. https://doi.org/10.1007/s13726-020-00857-x
    19. Guanghui Ma, Hua Yue. Advances in Uniform Polymer Microspheres and Microcapsules: Preparation and Biomedical Applications. Chinese Journal of Chemistry 2020, 38 (9) , 911-923. https://doi.org/10.1002/cjoc.202000135
    20. Yi Wei, Youbin Wu, Kang Wen, Nardana Bazybek, Guanghui Ma. Recent research and development of local anesthetic-loaded microspheres. Journal of Materials Chemistry B 2020, 8 (30) , 6322-6332. https://doi.org/10.1039/D0TB01129K
    21. Bradley S Miller, Eric Velazquez, Kevin C J Yuen. Long-Acting Growth Hormone Preparations – Current Status and Future Considerations. The Journal of Clinical Endocrinology & Metabolism 2020, 105 (6) , e2121-e2133. https://doi.org/10.1210/clinem/dgz149
    22. Mingzhu Ding, Biqiang Chen, Xiaojun Ji, Jingwen Zhou, Huiyuan Wang, Xiwei Tian, Xudong Feng, Hua Yue, Yongjin Zhou, Hailong Wang, Jianping Wu, Pengpeng Yang, Yu Jiang, Xuming Mao, Gang Xiao, Cheng Zhong, Wenhai Xiao, Bingzhi Li, Lei Qin, Jingsheng Cheng, Mingdong Yao, Ying Wang, Hong Liu, Lin Zhang, Linling Yu, Tao Chen, Xiaoyan Dong, Xiaoqiang Jia, Songping Zhang, Yanfeng Liu, Yong Chen, Kequan Chen, Jinglan Wu, Chenjie Zhu, Wei Zhuang, Sheng Xu, Pengfei Jiao, Lei Zhang, Hao Song, Sheng Yang, Yan Xiong, Yongquan Li, Youming Zhang, Yingping Zhuang, Haijia Su, Weiping Fu, Yingming Huang, Chun Li, Zongbao K. Zhao, Yan Sun, Guo-Qiang Chen, Xueming Zhao, He Huang, Yuguo Zheng, Lirong Yang, Zhiguo Su, Guanghui Ma, Hanjie Ying, Jian Chen, Tianwei Tan, Yingjin Yuan. Biochemical engineering in China. Reviews in Chemical Engineering 2019, 35 (8) , 929-993. https://doi.org/10.1515/revce-2017-0035
    23. Nan Li, Ari M. Chow, Hashwin V. S. Ganesh, Melanie Ratnam, Ian R. Brown, Kagan Kerman. Diazonium-Modified Screen-Printed Electrodes for Immunosensing Growth Hormone in Blood Samples. Biosensors 2019, 9 (3) , 88. https://doi.org/10.3390/bios9030088
    24. Danyela Francine Benvenutti, Tania Mari Bellé Bresolin, Rogerio Corrêa, Stefano Giovagnoli, Riccardo Vivani, Maurizio Ricci. A Novel Stabilizing Approach to Improve the Manufacturing of Biodegradable Microparticles Entrapping Plasticizing Active Molecules: the Case of 4-Methoxychalcone. Journal of Pharmaceutical Innovation 2019, 14 (2) , 159-175. https://doi.org/10.1007/s12247-018-9346-9
    25. Xiangyu Zheng, Hongli Li, Yi He, Mingwei Yuan, Meili Shen, Renyu Yang, Nianfeng Jiang, Minglong Yuan, Cui Yang. Preparation and In Vitro Release of Total Alkaloids from Alstonia Scholaris Leaves Loaded mPEG-PLA Microspheres. Materials 2019, 12 (9) , 1457. https://doi.org/10.3390/ma12091457
    26. Zhiying Yu, Lin Huang, Ruiting Wen, Yuzhen Li, Qiang Zhang. Preparation and in vivo pharmacokinetics of rhGH-loaded PLGA microspheres. Pharmaceutical Development and Technology 2019, 24 (4) , 395-401. https://doi.org/10.1080/10837450.2018.1502316
    27. Rohollah Ghasemi, Mahdi Abdollahi, Elaheh Emamgholi Zadeh, Khosrow Khodabakhshi, Ali Badeli, Hamed Bagheri, Saman Hosseinkhani. mPEG-PLA and PLA-PEG-PLA nanoparticles as new carriers for delivery of recombinant human Growth Hormone (rhGH). Scientific Reports 2018, 8 (1) https://doi.org/10.1038/s41598-018-28092-8
    28. Bathabile Ramalapa, Oscar Crasson, Marylène Vandevenne, Alain Gibaud, Emmanuel Garcion, Thomas Cordonnier, Moreno Galleni, Frank Boury. Protein–polysaccharide complexes for enhanced protein delivery in hyaluronic acid templated calcium carbonate microparticles. Journal of Materials Chemistry B 2017, 5 (35) , 7360-7368. https://doi.org/10.1039/C7TB01538K
    29. A Thorsted, P Thygesen, H Agersø, T Laursen, M Kreilgaard. Translational mixed‐effects PKPD modelling of recombinant human growth hormone – from hypophysectomized rat to patients. British Journal of Pharmacology 2016, 173 (11) , 1742-1755. https://doi.org/10.1111/bph.13473
    30. H. Bunjes, C. C. Müller-Goymann. Microsystems for Emulsification. 2016, 153-179. https://doi.org/10.1007/978-3-319-26920-7_5
    31. Chenhui Wang, Changhui Yu, Jiaxin Liu, Lesheng Teng, Fengying Sun, Youxin Li. Preparation and in vivo evaluation of PCADK/PLGA microspheres for improving stability and efficacy of rhGH. International Journal of Pharmaceutics 2015, 495 (2) , 924-931. https://doi.org/10.1016/j.ijpharm.2015.10.003
    32. Jie Wu, Qingze Fan, Yufei Xia, Guanghui Ma. Uniform-sized particles in biomedical field prepared by membrane emulsification technique. Chemical Engineering Science 2015, 125 , 85-97. https://doi.org/10.1016/j.ces.2014.08.016
    33. O. Germershaus, T. Lühmann, J.-C. Rybak, J. Ritzer, L. Meinel. Application of natural and semi-synthetic polymers for the delivery of sensitive drugs. International Materials Reviews 2015, 60 (2) , 101-131. https://doi.org/10.1179/1743280414Y.0000000045
    34. Guanghui Ma. Microencapsulation of protein drugs for drug delivery: Strategy, preparation, and applications. Journal of Controlled Release 2014, 193 , 324-340. https://doi.org/10.1016/j.jconrel.2014.09.003
    35. Samir Mitragotri, Paul A. Burke, Robert Langer. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nature Reviews Drug Discovery 2014, 13 (9) , 655-672. https://doi.org/10.1038/nrd4363
    36. Zhimei Song, Wenxia Zhu, Na Liu, Fengying Yang, Runliang Feng. Linolenic acid-modified PEG-PCL micelles for curcumin delivery. International Journal of Pharmaceutics 2014, 471 (1-2) , 312-321. https://doi.org/10.1016/j.ijpharm.2014.05.059
    37. María E Díaz, Johanna G Miquet, Soledad P Rossi, Pablo E Irene, Ana I Sotelo, Mónica B Frungieri, Daniel Turyn, Lorena González. GH administration patterns differently regulate epidermal growth factor signaling. Journal of Endocrinology 2014, 221 (2) , 309-323. https://doi.org/10.1530/JOE-13-0447
    38. Manolya Kukut, Oksan Karal-Yilmaz, Yusuf Yagci. Synthesis, characterisation and drug release properties of microspheres of polystyrene with aliphatic polyester side-chains. Journal of Microencapsulation 2014, 31 (3) , 254-261. https://doi.org/10.3109/02652048.2013.834993
    39. Ying Lu, Michael Sturek, Kinam Park. Microparticles produced by the hydrogel template method for sustained drug delivery. International Journal of Pharmaceutics 2014, 461 (1-2) , 258-269. https://doi.org/10.1016/j.ijpharm.2013.11.058

    Molecular Pharmaceutics

    Cite this: Mol. Pharmaceutics 2012, 9, 7, 2039–2048
    Click to copy citationCitation copied!
    https://doi.org/10.1021/mp300126t
    Published June 2, 2012
    Copyright © 2012 American Chemical Society

    Article Views

    1435

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.