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Dependence of pharmacokinetics and biodistribution on polymer architecture: effect of cyclic versus linear polymers.

ABSTRACT: The ability of a polymer to reptate through a nanopore has an influence on its circulatory half-life and biodistribution, since many physiological barriers contain nanopores. A cyclic polymer lacks chain ends, and therefore, cyclic polymers with molecular weights greater than the renal threshold for elimination should circulate longer than their linear-polymer counterparts when injected into animals. As predicted, radiolabeled cyclic polymers with molecular weights greater than the renal threshold have longer blood circulation times in mice than do linear polymers of comparable molecular weight.

SUBMITTER: Nasongkla N

PROVIDER: S-EPMC2668136 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Dependence of pharmacokinetics and biodistribution on polymer architecture: effect of cyclic versus linear polymers.

Nasongkla Norased N Chen Bo B Macaraeg Nichole N Fox Megan E ME Fréchet Jean M J JM Szoka Francis C FC

Journal of the American Chemical Society 20090301 11

The ability of a polymer to reptate through a nanopore has an influence on its circulatory half-life and biodistribution, since many physiological barriers contain nanopores. A cyclic polymer lacks chain ends, and therefore, cyclic polymers with molecular weights greater than the renal threshold for elimination should circulate longer than their linear-polymer counterparts when injected into animals. As predicted, radiolabeled cyclic polymers with molecular weights greater than the renal thresho ...[more]

PMID: 19256497

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Project description:The development of therapeutics for pediatric use has advanced in the last few decades, yet the off-label use of adult medications in pediatrics remains a significant clinical problem. Nano-based medicines are important drug delivery systems that can improve the bioavailability of a range of therapeutics. However, the use of nano-based medicines for application in pediatric populations is challenged by the lack of pharmacokinetic (PK) data in this population. To address this data gap, we investigated the PK of polymer-based nanoparticles in term-equivalent neonatal rats. We used poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles, which are polymer nanoparticles that have been extensively studied in adult populations but less commonly applied in neonates and pediatrics. We quantified the PK parameters and biodistribution of PLGA-PEG nanoparticles in term-equivalent healthy rats and revealed the PK and biodistribution of polymeric nanoparticles in neonatal rats. We further explored the effects of surfactant used to stabilize PLGA-PEG particles on PK and biodistribution. We showed that 4 h post intraperitoneal injection, nanoparticles had the highest accumulation in serum, at 54.0% of the injected dose for particles with Pluronic® F127 (F127) as the stabilizer and at 54.6% of the injected dose for particles with Poloxamer 188 (P80) as the stabilizer. The half-life of the F127-formulated PLGA-PEG particles was 5.9 h, which was significantly longer than the 1.7 h half-life of P80-formulated PLGA-PEG particles. Among all organs, the liver had the highest nanoparticle accumulation. At 24 h after administration, the accumulation of F127-formulated PLGA-PEG particles was at 26.2% of the injected dose, and the accumulation of P80-formulated particles was at 24.1% of the injected dose. Less than 1% of the injected nanoparticles was observed in healthy rat brain for both F127- and P80-formulated particles. These PK data inform the use of polymer nanoparticle applications in the neonate and provide a foundation for the translation of polymer nanoparticles for drug delivery in pediatric populations.

Dataset Information

Dependence of pharmacokinetics and biodistribution on polymer architecture: effect of cyclic versus linear polymers.

Publications

Dependence of pharmacokinetics and biodistribution on polymer architecture: effect of cyclic versus linear polymers.

Similar Datasets

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