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

Biomaterials (2012-08-22)
Chunbai He, Lichen Yin, Cui Tang, Chunhua Yin
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Atto Rho14 NHS ester
Sigma-Aldrich
Atto Rho11
Sigma-Aldrich
Atto Rho11 maleimide
Sigma-Aldrich
Atto Rho11 Biotin

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