Journal
JOURNAL OF CONTROLLED RELEASE
Volume 311, Issue -, Pages 74-84Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2019.08.036
Keywords
Aminoclay; Protein drug; Oral delivery; Absorption; Nano-carrier
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2016R1A2B2010097, 2019R1A2C2004873, 2018R1A5A2023127]
- National Research Foundation of Korea [2019R1A2C2004873, 2018R1A5A2023127, 2016R1A2B2010097] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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This research aimed to develop a pH-responsive organic-inorganic hybrid nanocomposite as an effective oral delivery system for protein drugs. Three different nanocomposites were prepared by using bovine serum albumin (BSA) as a model protein. A nanocomplex of BSA with 3-aminopropyl functionalized magnesium phyllosilicate (AC-BSA) was obtained via the spontaneous co-assembly and then sequentially coated with glycol-chitosan (GAC-BSA) and the pH sensitive polymer, Eudragit (R) L100-55 (EGAC-BSA). These organic-inorganic hybrid nanocomposites exhibited high entrapment efficiency (86-99%) and their structural characteristics were confirmed by using energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and circular dichroism analysis, indicating that the secondary structure of BSA was well retained in the nanocomposites. At pH 1.2, AC-BSA achieved rapid drug release of about 80% within 2 h, while GAC-BSA and EGAC-BSA exhibited slow drug release of 30% and 15%, respectively, indicating that the surface-coated nanocomposites were more stable in the gastric condition. Furthermore, the conformational stability of BSA entrapped in EGAC-BSA was well retained in the presence of proteolytic enzymes, suggesting that EGAC-BSA should be effective in protecting the protein against gastrointestinal harsh environment. Compared to free BSA, all of tested nanocomposites demonstrated 2.1-3.8-fold higher cellular uptake in Caco-2 cells. Furthermore, energy-dependent endocytosis and paracellular pathway contributed to the cellular transport of nanoparticles. After oral administration in rats, EGAC-BSA significantly enhanced the intestinal permeation of BSA compared to free BSA. In conclusion, EGAC-BSA appears to be promising as an effective oral delivery system for proteins with enhanced intestinal absorption.
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