Chokshi Nimitt, Vinchhi Preksha, Chauhan Shreyansh, Patel Mayur
Nirma University Institute of Pharmacy, Department of Pharmaceutics, Gujarat, India.
Turk J Pharm Sci. 2025 May 14;22(2):91-103. doi: 10.4274/tjps.galenos.2025.66350.
Tuberculosis (TB) remains a major worldwide health challenge causing morbidity and mortality, necessitating novel approaches for its effective therapy. Pyrazinamide (PYZ), a nicotinamide analogue, is a key frontline drug significantly involved in the treatment of TB. However, its dose-dependent hepatotoxicity is a major concern that needs to be addressed. The aim of the current research was to develop PYZ-loaded solid lipid nanoparticles (PYZ-SLNs) as a potential therapeutic intervention for treating TB.
The PYZ-SLNs were formulated by a high-pressure homogenization technique and optimized using a 23-factorial design. The drug concentration, emulsifier concentration, and homogenization cycles were considered critical formulation and processing parameters to study their effects on essential attributes of quality of PYZ-SLNs, i.e., entrapment efficiency (EE%), drug loading (DL%), and particle size.
The optimized PYZ-SLNs showed a particle size of 401±08 nm, EE% of 86.24±1.15, DL% of 14.38±0.85. The lipolysis studies revealed that PYZ-SLNs exhibited an anti-lipolytic effect due to stabilization by poloxamer 188. Moreover, the gastrointestinal (GI) stability results demonstrated that the PYZ-SLNs were stable in GI tract media (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4). The drug release studies showed the best fit with the Hixon-Crowell model. The accelerated stability studies revealed no significant changes in PYZ-SLNs for 6 months.
PYZ-SLNs could be a promising carrier for the treatment of TB via the oral intestinal lymphatic pathway, circumventing its hepatic first-pass metabolism and thereby preventing hepatic adverse effects.
结核病（TB）仍然是一项重大的全球健康挑战，会导致发病和死亡，因此需要新的有效治疗方法。吡嗪酰胺（PYZ）是一种烟酰胺类似物，是治疗结核病的关键一线药物。然而，其剂量依赖性肝毒性是一个需要解决的主要问题。本研究的目的是开发负载PYZ的固体脂质纳米粒（PYZ-SLNs）作为治疗结核病的潜在治疗干预措施。
采用高压均质技术制备PYZ-SLNs，并使用23析因设计进行优化。将药物浓度、乳化剂浓度和均质循环视为关键的制剂和工艺参数，以研究它们对PYZ-SLNs质量基本属性的影响，即包封率（EE%）、载药量（DL%）和粒径。
优化后的PYZ-SLNs粒径为401±08 nm，EE%为86.24±1.15，DL%为14.38±0.85。脂解研究表明，由于泊洛沙姆188的稳定作用，PYZ-SLNs表现出抗脂解作用。此外，胃肠道（GI）稳定性结果表明，PYZ-SLNs在胃肠道介质（pH 1.2、pH 4.5、pH 6.8和pH 7.4）中稳定。药物释放研究表明，其最符合希克森-克劳威尔模型。加速稳定性研究表明，PYZ-SLNs在6个月内无显著变化。
PYZ-SLNs可能是一种有前途的载体，可通过口服肠道淋巴途径治疗结核病，规避其肝脏首过代谢，从而预防肝脏不良反应。
