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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

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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.

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ACKNOWLEDGMENTS

This work was supported by a grant of the Korean Health Technology R&D Project, Ministry for Health, Welfare & Family Affairs (A092018), and by a grant of the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (no. 2010–0028167).

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Authors and Affiliations

  1. College of Pharmacy, Pusan National University, 30 Jangjeon-dong, Geumjeong-gu, Busan, 609–735, Republic of Korea

    Hyunuk Kim, Juho Lee & Yu Seok Youn

  2. College of Pharmacy, Sungkyunkwan University, 300 Chonchon-dong, Jangan-ku, Suwon City, 440–746, Republic of Korea

    Tae Hyung Kim, Eun-Seok Park & Kang Choon Lee

  3. Division of Biotechnology, The Catholic University of Korea, 43–1 Yeokgok 2-dong, Wonmi-gu, Bucheon-si, Gyeonggi-do, 420–743, Republic of Korea

    Eun Seong Lee

  4. College of Pharmacy, Chung-Ang University, 221 Heukseok dong, Dongjak-gu, Seoul, 155–756, Republic of Korea

    Kyung Taek Oh

  5. Department of Internal Medicine, Inha University, 253 Yonghyun-dong Nam-gu, Incheon, 402–751, Republic of Korea

    Don Haeng Lee

  6. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 315, Salt Lake City, Utah, 84108, USA

    You Han Bae

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  1. Hyunuk Kim
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Correspondence to Yu Seok Youn.

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Kim, H., Lee, J., Kim, T.H. et al. 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. Pharm Res 28, 2008–2019 (2011). https://doi.org/10.1007/s11095-011-0427-4

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  • DOI: https://doi.org/10.1007/s11095-011-0427-4

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