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

• Published in: Journal of colloid and interface science 2016-10, Vol.480, p.102-108
• Main Authors: Lee, Song Yi, Jung, Eunjae, Park, Ju-Hwan, Park, Jin Woo, Shim, Chang-Koo, Kim, Dae-Duk, Yoon, In-Soo, Cho, Hyun-Jong
• Format: Article
• Language: English
• Subjects: Animals; Chitosan; Chitosan - administration & dosage; Chitosan - blood; Chitosan - chemistry; Chitosan - pharmacokinetics; Female; Humans; Intravenous injection; Lactic Acid - administration & dosage; Lactic Acid - blood; Lactic Acid - chemistry; Lactic Acid - pharmacokinetics; Lung - metabolism; Lung targeting; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - metabolism; Particle Size; PLGA; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Polyglycolic Acid - pharmacokinetics; Rats; Surface Properties; Tissue Distribution; Transient aggregation
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2016.07.006

[Display omitted] 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.