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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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/4/1176 |
| _version_ | 1797603912941830144 |
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| author | Nuo Xu Megan Wong Gabrielle Balistreri Elizabeth Nance |
| author_facet | Nuo Xu Megan Wong Gabrielle Balistreri Elizabeth Nance |
| author_sort | Nuo Xu |
| collection | DOAJ |
| 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<sup>®</sup> 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. |
| first_indexed | 2024-03-11T04:38:47Z |
| format | Article |
| id | doaj.art-edd51cfd45a44c80a53d351c360ef2e1 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T04:38:47Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-edd51cfd45a44c80a53d351c360ef2e12023-11-17T20:53:48ZengMDPI AGPharmaceutics1999-49232023-04-01154117610.3390/pharmaceutics15041176Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of SurfactantNuo Xu0Megan Wong1Gabrielle Balistreri2Elizabeth Nance3Department of Chemical Engineering, University of Washington, Seattle, WA 98195, USADepartment of Chemical Engineering, University of Washington, Seattle, WA 98195, USAMolecular Engineering & Sciences Institute, University of Washington, Seattle, WA 98195, USADepartment of Chemical Engineering, University of Washington, Seattle, WA 98195, USAThe 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<sup>®</sup> 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.https://www.mdpi.com/1999-4923/15/4/1176nanomedicinepediatricsdrug deliveryhalf-lifenanoparticle accumulationclinical translation |
| spellingShingle | Nuo Xu Megan Wong Gabrielle Balistreri Elizabeth Nance Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant Pharmaceutics nanomedicine pediatrics drug delivery half-life nanoparticle accumulation clinical translation |
| 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 | nanomedicine pediatrics drug delivery half-life nanoparticle accumulation clinical translation |
| url | https://www.mdpi.com/1999-4923/15/4/1176 |
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