Kattel Prabhat, Sulthana Shoukath, Trousil Jiří, Shrestha Dinesh, Pearson David, Aryal Santosh
Department of Pharmaceutical Sciences and Health Outcomes, The Ben and Maytee Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, Texas 75799, United States.
Institute of Macromolecular Chemistry, Czech Academy of Sciences, Prague 16200, Czech Republic.
ACS Omega. 2023 Jul 19;8(30):27146-27155. doi: 10.1021/acsomega.3c02273. eCollection 2023 Aug 1.
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--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.
可生物降解且具有生物相容性的聚合物纳米颗粒（NPs）是提高药物生物利用度、降低内在毒性以及靶向目标位点的关键工具。最重要的是，聚合物合成简便且可通过衍生化添加功能特性，使其有可能理想地满足预期治疗应用的要求。在众多聚合物中，美国食品药品监督管理局（US FDA）批准的聚（l-乳酸-乙醇酸）共聚物（PLGA）是药物递送和可植入生物材料中广泛使用的生物相容性和可生物降解共聚物。虽然已经进行了许多使用PLGA NPs作为药物递送系统的研究，但对于理解NP重量对细胞行为（如摄取）的影响关注较少。在此，我们讨论了具有不同NP重量的PLGA NPs的合成及其胶体和生物学特性。通过纳米沉淀法，我们通过改变系统中初始PLGA的进料量，合成了尺寸范围为60至100 nm的PLGA NPs。发现这些NPs在胶体条件下长时间稳定。我们进一步研究了细胞摄取，发现这些NPs具有细胞相容性；然而，它们被癌细胞和免疫细胞的摄取存在差异，这受到NPs重量的极大影响。以阿霉素（DOX）作为模型药物评估了这些纳米颗粒（NPs）的药物递送潜力，将其以7.0±0.5 wt%的浓度负载到NP核心中以研究其治疗效果。结果表明，浓度和治疗时间都是发挥治疗效果的关键因素，如DOX-NPs在较低浓度下表现出更高的效力。观察结果显示，与游离DOX治疗组相比，DOX-NPs对DOX的细胞摄取更高。这将使我们能够降低推荐剂量以达到预期效果，否则使用游离DOX治疗时需要大剂量。考虑到基于PLGA纳米颗粒药物递送系统的重要性，我们预计这项研究将有助于为纳米颗粒的治疗应用建立设计考量和指导原则。
