Kundavarapu Narendra, Mahalingam Kannadasan, Yada Kiran Kumar
Motherhood University Faculty of Pharmaceutical Sciences, Department of Pharmaceutics, Uttarakhand, India.
Gate Institute of Pharmaceutical Sciences, Telangana, India.
Turk J Pharm Sci. 2025 Sep 5;22(4):246-260. doi: 10.4274/tjps.galenos.2025.36559.
Bortezomib (BTZ) functions as an androgen receptor signalling inhibitor, is used for the treatment of prostate cancer, and has been sanctioned by the United States Food and Drug Administration. The medicinal applications of BTZ are impeded by low solubility, first-pass metabolism, and restricted bioavailability. This study aimed to develop and enhance polylactic acid-co-glycolic acid (PLGA) nanobubbles (NBs) as a sustained-release mechanism for BTZ, thereby augmenting stability and bioavailability.
Seventeen experimental runs were conducted to optimize drug-PLGA NBs using a three-factor, three-level Box-Behnken Design. The improved formulation comprised 30 mg of medication, 250 mg of PLGA, and 2.0% polyvinyl alcohol as a stabilizing agent.
The NBs exhibited a particle size of 186.9±13.9 nm, a polydispersity index of 0.146±0.042, and a zeta potential of -21.4±2.28 mV, along with an entrapment efficiency of 66.12±1.48%. Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction analysis verified the absence of drug-polymer interactions, whereas scanning electron microscopy demonstrated uniform spherical nanoparticles. experiments demonstrated superior drug release, and stability assessments indicated no major alterations after one month. Pharmacokinetic studies in rats demonstrated an elevated C (1.69) and area under the curve from time 0 to t (1.63), signifying enhanced sustained release and absorption. The results underscore the capability of BTZ-loaded PLGA NBs to augment drug kinetics and bioavailability, hence facilitating targeted distribution and enhanced therapeutic efficacy.
This investigation offered significant insights into the factors influencing oral absorption in NB formulations, which can guide future methods for oral medication development. BTZ-loaded PLGA nanobubbles showed promising results by enhancing oral absorption and improving pharmacokinetics in the study, which points to their potential use in sustained-release drug delivery. These findings offer a stepping stone toward nanomedicine via the oral route in future drug development.
硼替佐米（BTZ）作为一种雄激素受体信号抑制剂，用于治疗前列腺癌，已获美国食品药品监督管理局批准。BTZ的药用因溶解度低、首过代谢和生物利用度受限而受到阻碍。本研究旨在开发并增强聚乳酸-乙醇酸共聚物（PLGA）纳米泡（NBs）作为BTZ的缓释机制，从而提高其稳定性和生物利用度。
采用三因素三水平Box-Behnken设计进行17次实验运行，以优化载药PLGA纳米泡。改进后的制剂包含30mg药物、250mg PLGA和2.0%聚乙烯醇作为稳定剂。
纳米泡的粒径为186.9±13.9nm，多分散指数为0.146±0.042，zeta电位为-21.4±2.28mV，包封率为66.12±1.48%。傅里叶变换红外光谱、差示扫描量热法和X射线衍射分析证实不存在药物-聚合物相互作用，而扫描电子显微镜显示为均匀的球形纳米颗粒。体外实验显示出优异的药物释放，稳定性评估表明一个月后无重大变化。大鼠体内药代动力学研究显示Cmax升高（1.69倍），0至t时刻的曲线下面积增加（1.63倍），表明缓释和吸收增强。结果强调了载有BTZ的PLGA纳米泡增强药物动力学和生物利用度的能力，从而促进靶向分布并提高治疗效果。
本研究为影响纳米泡制剂口服吸收的因素提供了重要见解，可指导未来口服药物开发方法。在本研究中，载有BTZ的PLGA纳米泡通过增强口服吸收和改善药代动力学显示出有前景的结果，这表明它们在缓释药物递送中的潜在用途。这些发现为未来药物开发中通过口服途径实现纳米医学提供了一块垫脚石。
