Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant.
Neonatal Pharmacokinetics and Biodistribution of Polymeric Nanoparticles and Effect of Surfactant.
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DOI：
10.3390/pharmaceutics15041176
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发表时间：
2023-04-07
期刊：
影响因子：
5.4
通讯作者：
Nance E
中科院分区：
文献类型：
--
作者：
Xu N;Wong M;Balistreri G;Nance E
在过去的几十年里，儿科治疗药物的开发取得了进展，但儿科成人药物的标签外使用仍然是一个重要的临床问题。纳米药物是重要的药物传递系统，可以提高一系列治疗药物的生物利用度。然而，由于缺乏儿科人群的药代动力学（PK）数据，纳米药物在儿科人群中的应用面临挑战。为了解决这一数据缺口，我们研究了基于聚合物的纳米颗粒在足月新生大鼠中的PK。我们使用聚（乳酸-羟基乙酸）-聚（乙二醇）（PLGA-PEG）纳米颗粒，这是一种聚合物纳米颗粒，已在成人人群中进行了广泛研究，但在新生儿和儿科中的应用较少。我们定量了PLGA-PEG纳米颗粒在足月健康大鼠中的PK参数和生物分布，并揭示了聚合物纳米颗粒在新生大鼠中的PK和生物分布。我们进一步探索了用于稳定PLGA-PEG颗粒的表面活性剂对PK和生物分布的影响。我们表明，腹膜内注射后4小时，纳米颗粒在血清中具有最高的积累，对于具有Pluronic® F127（F127）作为稳定剂的颗粒，为注射剂量的54.0%，对于具有泊洛沙姆188（P80）作为稳定剂的颗粒，为注射剂量的54.6%。F127配制的PLGA-PEG颗粒的半衰期为5.9小时，其显著长于P80配制的PLGA-PEG颗粒的1.7小时半衰期。在所有器官中，肝脏具有最高的纳米颗粒积累。在给药后24小时，F127配制的PLGA-PEG颗粒的蓄积为注射剂量的26.2%，P80配制的颗粒的蓄积为注射剂量的24.1%。对于F127和P80配制的颗粒，在健康大鼠脑中观察到小于1%的注射的纳米颗粒。这些PK数据为聚合物纳米颗粒在新生儿中的应用提供了信息，并为聚合物纳米颗粒在儿科人群中的药物递送提供了基础。
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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DOI：
10.3390/ma14123197
发表时间：
2021-06-10
期刊：
Materials (Basel, Switzerland)
影响因子：
--
作者：
Cortés H;Hernández-Parra H;Bernal-Chávez SA;Prado-Audelo MLD;Caballero-Florán IH;Borbolla-Jiménez FV;González-Torres M;Magaña JJ;Leyva-Gómez G
通讯作者：
Leyva-Gómez G
影响因子：
4.9
作者：
Alexis F;Pridgen E;Molnar LK;Farokhzad OC
通讯作者：
Farokhzad OC
地塞米松的块共聚物纳米颗粒会诱导白血病细胞死亡并增强治疗功效：一种新的小儿纳米医学应用。
影响因子：
4.9
作者：
Krishnan V;Xu X;Barwe SP;Yang X;Czymmek K;Waldman SA;Mason RW;Jia X;Rajasekaran AK
通讯作者：
Rajasekaran AK
影响因子：
8
作者：
Frattarelli, Daniel A. C.;Galinkin, Jeffrey L.;Del Monte, Mark
通讯作者：
Del Monte, Mark
影响因子：
4.9
作者：
Li, Shyh-Dar;Huang, Leaf
通讯作者：
Huang, Leaf