<p>Construction and in vivo/in vitro evaluation of a nanoporous ion-responsive targeted drug delivery system for recombinant human interferon Œ±-2b delivery</p>
Authors: Yueping Ding
Jie Zhu
Pengyue Bao
Thomas J Webster
Hongfei Liu
Yan Shen
Ying Xu
Journal: International Journal of Nanomedicine (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: ion exchange technique; ion-responsive; lung targeting; nanoporous; recombinant human interferon Œ±-2b
Affiliations: College of Pharmacy, Jiangsu University, Zhenjiang 212013, People's Republic of China., Chia Tai Tianqing Pharmaceutical Group Co., Ltd, Nanjing 210023, People's Republic of China., Jiangsu Sihuan Biopharmaceutical Co., Ltd, Wuxi 214000, People's Republic of China., State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, People's Republic of China., Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA.

Abstract:  Background: Like most protein macromolecular drugs, the half-life of rhIFN…ë-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 rhIFNŒ±-2b and target it to the lung passively with sustained release. Chitosan rhIFNŒ±-2b carboxymethyl nanoporous microspheres (CS-rhIFNŒ±-2b-CCPM) were prepared by the column method. Here, an electrostatic self-assembly technique was undertaken to improve and sustain rhIFNŒ±-2b release rate. Results: The size distribution of the microspheres was 5~15 Œºm, and the microspheres contained nanopores 300~400 nm in diameter. The in vitro release results showed that rhIFNŒ±-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 rhIFNŒ±-2b. Results from inhibition rate experiments for A549 cell proliferation showed that the antitumor activity of CS-rhIFNŒ±-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-rhIFNŒ±-2b-CCPM can still be detected in vivo after 24 hrs, equivalent to the stock solution at 6 hrs, which indicated that CS-rhIFNŒ±-2b-CCPM had a certain sustained-release effect in vivo. The results of in vivo tissue distribution showed that CS-rhIFNŒ±-2b-CCPM was mainly concentrated in the lungs of mice (1.85 times the stock solution). The pharmacodynamics results showed that CS-rhIFNŒ±-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-rhIFNŒ±-2b-CCPM compared to the reference (the stock solution of rhIFNŒ±-2b), and, thus, should be further studied. 

Retracted: No

PubPeer comments:
 Figure 5G appears to have a repeated image. See red boxes. Image below is contrast enhanced. ***  , 
 Thank you for pointing this out and we are currently looking into this. Tom Webster , 
 Common authors on this paper: https: pubpeer.com publications 2939B96CE91DC2539CCBE1295B0207 , 
 #2 Is there an update on this investigation? Emails to this corresponding author (who is also the journalu2019s Editor in Chief) are currently generating an auto reply: u201cThank you for your message. I am currently on a leave of absence. Should you require immediate assistance please contact....u201d ,