Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery
Hongfei Liu,1 Jie Zhu,1 Pengyue Bao,2 Yueping Ding,3 Yan Shen,4 Thomas J Webster,5 Ying Xu11College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing 210023, People’s Republic of China; 3Jiangs...
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Dove Medical Press
2019
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oai:doaj.org-article:0fa1b39c66114f4fbf19bcc90d3b4a362021-12-02T09:27:12ZConstruction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery1178-2013https://doaj.org/article/0fa1b39c66114f4fbf19bcc90d3b4a362019-07-01T00:00:00Zhttps://www.dovepress.com/construction-and-in-vivoin-vitro-evaluation-of-a-nanoporous-ion-respon-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Hongfei Liu,1 Jie Zhu,1 Pengyue Bao,2 Yueping Ding,3 Yan Shen,4 Thomas J Webster,5 Ying Xu11College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing 210023, People’s Republic of China; 3Jiangsu Sihuan Biopharmaceutical Co., Ltd, Wuxi 214000, People’s Republic of China; 4State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 5Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USABackground: Like most protein macromolecular drugs, the half-life of rhIFNɑ-2b is short, with a low drug utilization rate, and the preparation and release conditions significantly affect its stability.Methods: A nanoporous ion-responsive targeted drug delivery system (PIRTDDS) was designed to improve drug availability of rhIFNα-2b and target it to the lung passively with sustained release. Chitosan rhIFNα-2b carboxymethyl nanoporous microspheres (CS-rhIFNα-2b-CCPM) were prepared by the column method. Here, an electrostatic self-assembly technique was undertaken to improve and sustain rhIFNα-2b release rate.Results: The size distribution of the microspheres was 5∼15 μm, and the microspheres contained nanopores 300∼400 nm in diameter. The in vitro release results showed that rhIFNα-2b and CCPM were mainly bound by ionic bonds. After self-assembling, the release mechanism was transformed into being membrane diffusion. The accumulative release amount for 24 hrs was 83.89%. Results from circular dichrogram and SDS-PAGE electrophoresis showed that there was no significant change in the secondary structure and purity of rhIFNα-2b. Results from inhibition rate experiments for A549 cell proliferation showed that the antitumor activity of CS-rhIFNα-2b-CCPM for 24 hrs retained 91.98% of the stock solution, which proved that the drug-loaded nanoporous microspheres maintained good drug activity. In vivo pharmacokinetic experimental results showed that the drugs in CS-rhIFNα-2b-CCPM can still be detected in vivo after 24 hrs, equivalent to the stock solution at 6 hrs, which indicated that CS-rhIFNα-2b-CCPM had a certain sustained-release effect in vivo. The results of in vivo tissue distribution showed that CS-rhIFNα-2b-CCPM was mainly concentrated in the lungs of mice (1.85 times the stock solution). The pharmacodynamics results showed that CS-rhIFNα-2b-CCPM had an obvious antitumor effect, and the tumor inhibition efficiency was 29.2%.Conclusion: The results suggested a novel sustained-release formulation with higher drug availability and better lung targeting from CS-rhIFNα-2b-CCPM compared to the reference (the stock solution of rhIFNα-2b), and, thus, should be further studied.Keywords: nanoporous, ion-responsive, recombinant human interferon α-2b, ion exchange technique, sustained release, lung targetingLiu HZhu JBao PDing YShen YWebster TJXu YDove Medical Pressarticlenano-porousion-responsiverecombinant human interferon α-2b (rhIFNα-2b)ion exchange techniquesustained releaselung targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5339-5353 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
nano-porous ion-responsive recombinant human interferon α-2b (rhIFNα-2b) ion exchange technique sustained release lung targeting Medicine (General) R5-920 |
| spellingShingle |
nano-porous ion-responsive recombinant human interferon α-2b (rhIFNα-2b) ion exchange technique sustained release lung targeting Medicine (General) R5-920 Liu H Zhu J Bao P Ding Y Shen Y Webster TJ Xu Y Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| description |
Hongfei Liu,1 Jie Zhu,1 Pengyue Bao,2 Yueping Ding,3 Yan Shen,4 Thomas J Webster,5 Ying Xu11College of Pharmacy, Jiangsu University, Zhenjiang 212013, People’s Republic of China; 2Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing 210023, People’s Republic of China; 3Jiangsu Sihuan Biopharmaceutical Co., Ltd, Wuxi 214000, People’s Republic of China; 4State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People’s Republic of China; 5Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USABackground: Like most protein macromolecular drugs, the half-life of rhIFNɑ-2b is short, with a low drug utilization rate, and the preparation and release conditions significantly affect its stability.Methods: A nanoporous ion-responsive targeted drug delivery system (PIRTDDS) was designed to improve drug availability of rhIFNα-2b and target it to the lung passively with sustained release. Chitosan rhIFNα-2b carboxymethyl nanoporous microspheres (CS-rhIFNα-2b-CCPM) were prepared by the column method. Here, an electrostatic self-assembly technique was undertaken to improve and sustain rhIFNα-2b release rate.Results: The size distribution of the microspheres was 5∼15 μm, and the microspheres contained nanopores 300∼400 nm in diameter. The in vitro release results showed that rhIFNα-2b and CCPM were mainly bound by ionic bonds. After self-assembling, the release mechanism was transformed into being membrane diffusion. The accumulative release amount for 24 hrs was 83.89%. Results from circular dichrogram and SDS-PAGE electrophoresis showed that there was no significant change in the secondary structure and purity of rhIFNα-2b. Results from inhibition rate experiments for A549 cell proliferation showed that the antitumor activity of CS-rhIFNα-2b-CCPM for 24 hrs retained 91.98% of the stock solution, which proved that the drug-loaded nanoporous microspheres maintained good drug activity. In vivo pharmacokinetic experimental results showed that the drugs in CS-rhIFNα-2b-CCPM can still be detected in vivo after 24 hrs, equivalent to the stock solution at 6 hrs, which indicated that CS-rhIFNα-2b-CCPM had a certain sustained-release effect in vivo. The results of in vivo tissue distribution showed that CS-rhIFNα-2b-CCPM was mainly concentrated in the lungs of mice (1.85 times the stock solution). The pharmacodynamics results showed that CS-rhIFNα-2b-CCPM had an obvious antitumor effect, and the tumor inhibition efficiency was 29.2%.Conclusion: The results suggested a novel sustained-release formulation with higher drug availability and better lung targeting from CS-rhIFNα-2b-CCPM compared to the reference (the stock solution of rhIFNα-2b), and, thus, should be further studied.Keywords: nanoporous, ion-responsive, recombinant human interferon α-2b, ion exchange technique, sustained release, lung targeting |
| format |
article |
| author |
Liu H Zhu J Bao P Ding Y Shen Y Webster TJ Xu Y |
| author_facet |
Liu H Zhu J Bao P Ding Y Shen Y Webster TJ Xu Y |
| author_sort |
Liu H |
| title |
Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| title_short |
Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| title_full |
Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| title_fullStr |
Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| title_full_unstemmed |
Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| title_sort |
construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon α-2b delivery |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/0fa1b39c66114f4fbf19bcc90d3b4a36 |
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