Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Punjab 63100, Pakistan.
Department of Pharmaceutics, Faculty of Pharmacy, The Islamia University of Bahawalpur, Punjab 63100, Pakistan.
Colloids Surf B Biointerfaces. 2024 Oct;242:114073. doi: 10.1016/j.colsurfb.2024.114073. Epub 2024 Jul 3.
Oral administration of BCS class IV anticancer agents has always remained challenging and frequently results in poor oral bioavailability. The goal of the current study was to develop hybrid nanoparticles (HNPs) employing cholesterol and poloxamer-407 to boost paclitaxel's (PTX) oral bioavailability. A series of HNPs with different cholesterol and poloxamer-407 ratios were developed utilizing a single-step nanoprecipitation technique. The PTX loaded HNPs were characterized systematically via particle size, zeta potential, polydispersity index, surface morphology, in vitro drug release, FTIR, DSC, XRD, acute oral toxicity analysis, hemolysis evaluation, accelerated stability studies, and in vivo pharmacokinetic analysis. The HNPs were found within the range of 106.6±55.60 - 244.5±88.24 nm diameter with the polydispersity index ranging from 0.20±0.03 - 0.51±0.11. SEM confirmed circular, nonporous, and smooth surfaces of HNPs. PTX loaded HNPs exhibited controlled release profile. The compatibility between the components of formulation, thermal stability, and amorphous nature of HNPs were confirmed by FTIR, DSC, and XRD, respectively. Acute oral toxicity analysis revealed that developed system have no deleterious effects on the animals' cellular structures. HNPs demonstrated notable cytotoxic effects and were hemocompatible at relatively higher concentrations. In vivo pharmacokinetic profile (AUC, AUMC, t and MRT) of the PTX loaded HNPs was improved as compared to pure PTX. It is concluded from our findings that the developed HNPs are hemocompatible, biocompatible and have significantly enhanced the oral bioavailability of PTX.
口服施用 BCS 分类 IV 类抗癌剂一直具有挑战性，并且经常导致口服生物利用度差。本研究的目的是开发使用胆固醇和泊洛沙姆 407 的混合纳米粒子 (HNP) 来提高紫杉醇 (PTX) 的口服生物利用度。使用单步纳米沉淀技术开发了具有不同胆固醇和泊洛沙姆 407 比例的一系列 HNP。通过粒径、zeta 电位、多分散指数、表面形态、体外药物释放、FTIR、DSC、XRD、急性口服毒性分析、溶血评价、加速稳定性研究和体内药代动力学分析对载药 HNP 进行了系统表征。发现 HNP 的粒径在 106.6±55.60-244.5±88.24nm 范围内，多分散指数在 0.20±0.03-0.51±0.11 范围内。SEM 证实 HNP 具有圆形、无孔和光滑的表面。载药 HNP 表现出控制释放特性。通过 FTIR、DSC 和 XRD 分别证实了制剂成分之间的相容性、热稳定性和 HNP 的无定形性质。急性口服毒性分析表明，所开发的系统对动物细胞结构没有有害影响。HNP 表现出显著的细胞毒性作用，并且在相对较高的浓度下具有血液相容性。与纯 PTX 相比，载药 HNP 的体内药代动力学特征（AUC、AUMC、t 和 MRT）得到改善。从我们的研究结果得出结论，所开发的 HNP 具有血液相容性、生物相容性，并显著提高了 PTX 的口服生物利用度。
