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Long-acting inhalable chitosan-coated poly(lactic-co-glycolic acid) nanoparticles containing hydrophobically modified exendin-4 for treating type 2 diabetes

Authors Lee C, Choi JS, Kim I, Oh KT, Lee ES, Park ES, Lee KC, Youn YS

Received 13 May 2013

Accepted for publication 10 June 2013

Published 9 August 2013 Volume 2013:8(1) Pages 2975—2983

DOI https://doi.org/10.2147/IJN.S48197

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Changkyu Lee,1 Ji Su Choi,1 Insoo Kim,1 Kyung Taek Oh,2 Eun Seong Lee,3 Eun-Seok Park,1 Kang Choon Lee,1 Yu Seok Youn1

1School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 2College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea; 3Division of Biotechnology, The Catholic University of Korea, Bucheon-si, Republic of Korea

Abstract: Inhalable glycol chitosan-coated poly(lactic-co-glycolic acid) (PLGA) nanoparticles containing palmitic acid-modified exendin-4 (Pal-Ex4) (chitosan Pal-Ex4 PLGA NPs) were prepared and characterized. The surface morphology, particle size, and zeta potential of chitosan Pal-Ex4 PLGA NPs were investigated, and the adsorption and cytotoxicity of chitosan Pal-Ex4 PLGA NPs were evaluated in human lung epithelial cells (A549). Finally, the lung deposition characteristics and hypoglycemia caused by chitosan Pal-Ex4 PLGA NPs were evaluated after pulmonary administration in imprinting control region (ICR) and type 2 diabetic db/db mice. Results showed that chitosan Pal-Ex4 PLGA NPs were spherical, compact and had a diameter of ~700 nm and a positive surface charge of +28.5 mV. Chitosan-coated PLGA NPs were adsorbed onto A549 cells much more so than non-coated PLGA NPs. Pal-Ex4 release from chitosan-coated PLGA NPs was delayed by as much as 1.5 days as compared with chitosan-coated Ex4 PLGA NPs. In addition, chitosan-coated PLGA NPs remained in the lungs for ~72 hours after pulmonary administration, whereas most non-coated PLGA NPs were lost at 8 hours after administration. Furthermore, the hypoglycemic efficacy of inhaled chitosan Pal-Ex4 PLGA NPs was 3.1-fold greater than that of chitosan Ex4 PLGA NPs in db/db mice. The authors believe chitosan Pal-Ex4 PLGA NPs have considerable potential as a long-acting inhalation delivery system for the treatment of type 2 diabetes.

Keywords: chitosan-coating, PLGA nanoparticles, inhalation, exendin-4, type 2 diabetes

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