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Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant

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 therape...

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Autores principales: Xu, Nuo, Wong, Megan, Balistreri, Gabrielle, Nance, Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140984/
https://www.ncbi.nlm.nih.gov/pubmed/37111661
http://dx.doi.org/10.3390/pharmaceutics15041176
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author Xu, Nuo
Wong, Megan
Balistreri, Gabrielle
Nance, Elizabeth
author_facet Xu, Nuo
Wong, Megan
Balistreri, Gabrielle
Nance, Elizabeth
author_sort Xu, Nuo
collection PubMed
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.
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spelling pubmed-101409842023-04-29 Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant Xu, Nuo Wong, Megan Balistreri, Gabrielle Nance, Elizabeth Pharmaceutics Article 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. MDPI 2023-04-07 /pmc/articles/PMC10140984/ /pubmed/37111661 http://dx.doi.org/10.3390/pharmaceutics15041176 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Nuo
Wong, Megan
Balistreri, Gabrielle
Nance, Elizabeth
Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title_full Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title_fullStr Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title_full_unstemmed Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title_short Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant
title_sort neonatal pharmacokinetics and biodistribution of polymeric nanoparticles and effect of surfactant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10140984/
https://www.ncbi.nlm.nih.gov/pubmed/37111661
http://dx.doi.org/10.3390/pharmaceutics15041176
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