Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles.
Effect of Nanoparticle Weight on the Cellular Uptake and Drug Delivery Potential of PLGA Nanoparticles.
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DOI：
10.1021/acsomega.3c02273
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发表时间：
2023-08-01
期刊：
影响因子：
4.1
通讯作者：
Aryal, Santosh
中科院分区：
文献类型：
--
作者：
Kattel, Prabhat;Sulthana, Shoukath;Trousil, Jiri;Shrestha, Dinesh;Pearson, David;Aryal, Santosh
生物可降解和生物相容的聚合物纳米颗粒(NPs)是提高药物生物利用度、降低固有毒性和靶向性的关键工具。最重要的是，聚合物的合成及其衍生以增加功能特性的简便性使其有可能成为满足预期治疗应用要求的理想材料。在众多聚合物中，美国食品和药物管理局批准的聚(L-乳酸-乙醇酸共聚)是一种广泛应用于药物释放和植入性生物材料的生物相容性和可生物降解的共聚聚合物。虽然利用PLGA纳米粒作为药物传递系统已经进行了许多研究，但对于了解纳米粒重量对细胞行为(如摄取)的影响的关注较少。在这里，我们讨论了不同NP重量的PLGA纳米粒子的合成及其胶体和生物学性质。在纳米沉淀法之后，通过改变体系中PLGA的初始进料，我们合成了PLGA纳米颗粒，尺寸从60到100 nm不等。这些纳米粒子在胶体条件下可以长时间稳定。我们进一步研究了细胞摄取，发现这些NPs是细胞相容的；然而，它们被癌细胞和免疫细胞差异摄取，这很大程度上受NPs重量的影响。以阿霉素(DOX)为模型药物，以7.0±0.5wt%的阿霉素为载药浓度，评价纳米粒的释药潜力，以研究其治疗效果。结果表明，浓度和处理时间都是显示治疗效果的关键因素，正如观察到的那样，DOX-NPs在较低浓度下显示出更高的效力。观察表明，与游离DOX治疗组相比，DOX-NPs对DOX的细胞摄取更高。这将使我们能够减少推荐剂量以达到预期的效果，否则使用游离DOX治疗时需要大剂量。考虑到基于PLGA的纳米药物传递系统的重要性，我们预计这项研究将有助于建立纳米颗粒治疗应用的设计考虑和指南。
Biodegradable and biocompatible polymeric nanoparticles (NPs) stand out as a key tool for improving drug bioavailability, reducing the inherent toxicity, and targeting the intended site. Most importantly, the ease of polymer synthesis and its derivatization to add functional properties makes them potentially ideal to fulfill the requirements for intended therapeutic applications. Among many polymers, US FDA-approved poly(l-lactic-co-glycolic) acid (PLGA) is a widely used biocompatible and biodegradable co-polymer in drug delivery and in implantable biomaterials. While many studies have been conducted using PLGA NPs as a drug delivery system, less attention has been given to understanding the effect of NP weight on cellular behaviors such as uptake. Here we discuss the synthesis of PLGA NPs with varying NP weights and their colloidal and biological properties. Following nanoprecipitation, we have synthesized PLGA NP sizes ranging from 60 to 100 nm by varying the initial PLGA feed in the system. These NPs were found to be stable for a prolonged period in colloidal conditions. We further studied cellular uptake and found that these NPs are cytocompatible; however, they are differentially uptaken by cancer and immune cells, which are greatly influenced by NPs’ weight. The drug delivery potential of these nanoparticles (NPs) was assessed using doxorubicin (DOX) as a model drug, loaded into the NP core at a concentration of 7.0 ± 0.5 wt % to study its therapeutic effects. The results showed that both concentration and treatment time are crucial factors for exhibiting therapeutic effects, as observed with DOX-NPs exhibiting a higher potency at lower concentrations. The observations revealed that DOX-NPs exhibited a higher cellular uptake of DOX compared to the free-DOX treatment group. This will allow us to reduce the recommended dose to achieve the desired effect, which otherwise required a large dose when treated with free DOX. Considering the significance of PLGA-based nanoparticle drug delivery systems, we anticipate that this study will contribute to the establishment of design considerations and guidelines for the therapeutic applications of nanoparticles.
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影响因子：
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作者：
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