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Size-dependent absorption mechanism of polymeric nanoparticles for oral delivery of protein drugs

Paper ID Volume ID Publish Year Pages File Format Full-Text
6922 524 2012 10 PDF Available
Title
Size-dependent absorption mechanism of polymeric nanoparticles for oral delivery of protein drugs
Abstract

Polymeric nanoparticles have been widely applied to oral delivery of protein drugs, however, few studies focused on the systematical elucidation of the size-dependent oral absorption mechanism with well-defined polymeric nanoparticles. Rhodamine B labeled carboxylated chitosan grafted nanoparticles (RhB-CCNP) with different particle sizes (300, 600, and 1000 nm) and similar Zeta potentials (−35 mV) were developed. FITC labeled bovine serum albumin (FITC-BSA) was encapsulated into RhB-CCNP to form drug loaded polymeric nanoparticles (RhB-CCNP-BSA). RhB-CCNP-BSA with uniform particle size and similar surface charge possessed desired structural stability in simulated physiological environment to substantially guarantee the validation of elucidation on size-dependent absorption mechanisms of polymeric nanoparticles using in vitro, in situ, and ex vivo models. RhB-CCNP-BSA with smaller sizes (300 nm) demonstrated elevated intestinal absorption, as mechanistically evidenced by higher mucoadhesion in rat ileum, release amount of the payload into the mucus layer, Caco-2 cell internalization, transport across Caco-2 cell monolayers and rat ileum, and systemic biodistribution after oral gavage. Peyer’s patches could play a role in the mucoadhesion of nanoparticles, resulting in their close association with the intestinal absorption of nanoparticles. These results provided guidelines for the rational design of oral nanocarriers for protein drugs in terms of particle size.

Keywords
Polymeric nanoparticles; Particle size; Oral absorption; Uptake; Transport; BiodistributionAPS, ammonium persulfate; CC, carboxylated chitosan; CCNP, carboxylated chitosan grafted nanoparticles; FAE, follicle-associated epithelium; FITC-BSA, FITC labeled
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Size-dependent absorption mechanism of polymeric nanoparticles for oral delivery of protein drugs
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 33, November 2012, Pages 8569–8578
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us