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Transient aggregation of chitosan-modified poly(d,l-lactic-co-glycolic) acid nanoparticles in the blood stream and improved lung targeting efficiency

Author:
Lee, Song Yi, Jung, Eunjae, Park, Ju-Hwan, Park, Jin Woo, Shim, Chang-Koo, Kim, Dae-Duk, Yoon, In-Soo, Cho, Hyun-Jong
Source:
Journal of colloid and interface science 2016 v.480 pp. 102-108
ISSN:
0021-9797
Subject:
binding capacity, blood flow, chitosan, evaporation, fluorescence, human serum albumin, image analysis, intravenous injection, lungs, mice, nanoparticles, particle size, polyacrylamide gel electrophoresis, rats, solvents, zeta potential
Abstract:
Chitosan (CS)-modified poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared and their lung targetability after intravenous administration was elucidated. PLGA NPs (mean diameter: 225nm; polydispersity index: 0.11; zeta potential: −15mV), 0.2% (w/v) CS-coated PLGA NPs (CS02-PLGA NPs, mean diameter: 264nm; polydispersity index: 0.17; zeta potential: −7mV), and 0.5% (w/v) CS-coated PLGA NPs (CS05-PLGA NPs, mean diameter: 338nm; polydispersity index: 0.23; zeta potential: 12mV) were fabricated by a modified solvent evaporation method. PLGA NPs maintained their initial particle size in different media, such as human serum albumin (HSA) solution, rat plasma, and distilled water (DW), while CS05-PLGA NPs exhibited the formation of aggregates in early incubation time and disassembly of those into the NPs in late incubation time (at 24h). According to the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, the binding affinity of CS05-PLGA NPs with HSA and rat plasma was higher than that of PLGA NPs. By a near-infrared fluorescence (NIRF) imaging test in the mouse, the selective accumulation of CS05-PLGA NPs, rather than PLGA NPs, in lung tissue was demonstrated. These findings suggest that CS05-PLGA NPs can form transient aggregates in the blood stream after intravenous administration and markedly improve lung targeting efficiency, compared with PLGA NPs.
Agid:
6058896