caa a22 4500 445313536 CHVBK 20180317142638.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s11095-011-0427-4 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0427-4 Albumin-Coated Porous Hollow Poly(Lactic-co-Glycolic Acid) Microparticles Bound with Palmityl-Acylated Exendin-4 as a Long-Acting Inhalation Delivery System for the Treatment of Diabetes [Elektronische Daten] [Hyunuk Kim, Juho Lee, Tae Kim, Eun Lee, Kyung Oh, Don Lee, Eun-Seok Park, You Bae, Kang Lee, Yu Youn] ABSTRACT: Purpose: To study the development of porous poly(lactic-co-glycolic acid) microparticles (PLGA MPs) coated initially with albumin and then with palmityl-acylated exendin-4 (Pal-Ex4) as an inhalation system for treating diabetes. Methods: Porous PLGA MPs were prepared by w/o/w double emulsification using hydroxypropyl-β-cyclodextrin and poly(ethylene-alt-maleic anhydride). Albumin was covalently attached to the MPs using EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide); Pal-Ex4 was then bound on the albumin surface. Albumin-binding degree and aerosolization efficiency were investigated. Deposition of the MPs after insufflations into the lungs of ICR mice was observed by image monitoring, and pulmonary hypoglycemic efficacies were examined in db/db mice. Cytotoxicity and histopathology induced by MPs were examined in Calu-3 and A549 cells and in the lungs of db/db mice, respectively. Results: Albumin-coating and Pal-Ex4-binding to porous MP were performed with acceptable efficiencies. Pal-Ex4-bound albumin-coated MPs (Pal-Ex4/HSA-PLGA MP) were of high porosity and had appropriate aerodynamic sizes. Furthermore, this MP was efficiently deposited throughout mouse lungs, and exhibited a prolonged hypoglycemia and no significant lung tissue damage in db/db mice. Conclusion: Pal-Ex4/HSA-PLGA MP demonstrated many meaningful pharmaceutical advantages for the treatment of diabetes, in terms of aerosolization efficiency, drug loading, sustained drug-release, and hypoglycemic duration in vivo. Springer Science+Business Media, LLC, 2011 albumin-binding nationallicence albumin-coating nationallicence inhalation nationallicence palmityl-acylated exendin-4 nationallicence porous microspheres nationallicence Kim Hyunuk College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut Lee Juho College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut Kim Tae College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut Lee Eun Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, 420-743, Gyeonggi-do, Republic of Korea aut Oh Kyung College of Pharmacy, Chung-Ang University, 221 Heukseok dong, Dongjak-gu, 155-756, Seoul, Republic of Korea aut Lee Don Department of Internal Medicine, Inha University, 253 Yonghyun-dong Nam-gu, 402-751, Incheon, Republic of Korea aut Park Eun-Seok College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut Bae You Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 315, 84108, Salt Lake City, Utah, USA aut Lee Kang College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut Youn Yu College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 2008-2019 0724-8741 28:8<2008 2011 28 11095 https://doi.org/10.1007/s11095-011-0427-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0427-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kim Hyunuk College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut NATIONALLICENCE 700 1- Lee Juho College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut NATIONALLICENCE 700 1- Kim Tae College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut NATIONALLICENCE 700 1- Lee Eun Division of Biotechnology, The Catholic University of Korea, 43-1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, 420-743, Gyeonggi-do, Republic of Korea aut NATIONALLICENCE 700 1- Oh Kyung College of Pharmacy, Chung-Ang University, 221 Heukseok dong, Dongjak-gu, 155-756, Seoul, Republic of Korea aut NATIONALLICENCE 700 1- Lee Don Department of Internal Medicine, Inha University, 253 Yonghyun-dong Nam-gu, 402-751, Incheon, Republic of Korea aut NATIONALLICENCE 700 1- Park Eun-Seok College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut NATIONALLICENCE 700 1- Bae You Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 315, 84108, Salt Lake City, Utah, USA aut NATIONALLICENCE 700 1- Lee Kang College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, 440-746, Suwon City, Republic of Korea aut NATIONALLICENCE 700 1- Youn Yu College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, 609-735, Busan, Republic of Korea aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/8(2011-08-01), 2008-2019 0724-8741 28:8<2008 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer