Puri Vishal, Chaudhary Kabi Raj, Singh Arti, Singh Charan
Department of Pharmaceutics, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India.
Department of Pharmacology, ISF College of Pharmacy, GT Road NH-95, Ghal Kalan, Moga, Punjab, 142001, India.
Curr Res Pharmacol Drug Discov. 2022 Jan 18;3:100084. doi: 10.1016/j.crphar.2022.100084. eCollection 2022.
Several studies have stated that mucus is a critical hurdle for drug delivery to the mucosal tissues. As a result, Polymeric nanoparticles that can overcome mucus barriers are gaining popularity for controlled drug delivery into intra-macrophages to attain high intracellular drug concentration. The present study was aimed to fabricate inhalable N-acetylcysteine (NAC) modified PLGA mucus penetrating particles using the double emulsion method (w/o/w) for target delivery to alveolar macrophages and minimize the dose-related adverse effects, efficiently encapsulate hydrophilic drug, sustain the release profile and prolong the retention time for the management of tuberculosis. Among the numerous formulations, the drug/polymer ratio of 1:10 with 0.50% PVA concentration and sonication time for 2 min s was chosen for further research. The formulated nanoparticles had a mean particle size of 307.50 ± 9.54 nm, PDI was 0.136 ± 0.02, zeta potential about -11.3 ± 0.4 mV, decent entrapment efficiency (55.46 ± 2.40%), drug loading (9.05 ± 0.22%), and excellent flowability. FTIR confirmed that NAC and PLGA were compatible with each other. SEM graphs elucidated that the nanoparticles were spherically shaped with a slightly rough surface whereas TEM analysis ensured the nanometer size nanoparticles and coating of lipid over NPs surface. PXRD spectrum concluded the transformation of the drug from crystalline to amorphous state in the formulation. release pattern was biphasic started with burst release (64.67 ± 1.53% within 12hrs) followed by sustained release over 48hrs thus enabling the prolonged replenishing of NAC. lung deposition study pronounced that coated NAC-PLGA-MPPs showed favorable results in terms of emitted dose (86.67 ± 2.52%), MMAD value (2.57 ± 0.12 μm), GSD value (1.55 ± 0.11 μm), and FPF of 62.67 ± 2.08% for the deposition and targeting the lungs. Finally, efficacy studies demonstrated that NAC-PLGA-MPPs presented more prominent antibacterial activity against H37Rv strain as compared to NAC. Hence, PLGA based particles could be a better strategy to deliver the NAC for lung targeting.
多项研究表明，黏液是药物递送至黏膜组织的关键障碍。因此，能够克服黏液屏障的聚合物纳米颗粒在将药物可控递送至巨噬细胞以实现高细胞内药物浓度方面越来越受到关注。本研究旨在采用双乳液法（w/o/w）制备可吸入的N-乙酰半胱氨酸（NAC）修饰的聚乳酸-羟基乙酸共聚物（PLGA）黏液穿透颗粒，以靶向递送至肺泡巨噬细胞并将剂量相关的不良反应降至最低，有效包封亲水性药物，维持释放曲线并延长滞留时间，用于结核病的治疗。在众多配方中，选择药物/聚合物比例为1:10、聚乙烯醇（PVA）浓度为0.50%且超声处理时间为2分钟的配方进行进一步研究。所制备的纳米颗粒平均粒径为307.50±9.54纳米，多分散指数（PDI）为0.136±0.02，zeta电位约为-11.3±0.4毫伏，具有良好的包封率（55.46±2.40%）、载药量（9.05±0.22%）和优异的流动性。傅里叶变换红外光谱（FTIR）证实NAC与PLGA相互兼容。扫描电子显微镜（SEM）图像表明纳米颗粒呈球形，表面略有粗糙，而透射电子显微镜（TEM）分析确定了纳米尺寸的纳米颗粒以及纳米颗粒表面的脂质涂层。粉末X射线衍射（PXRD）光谱表明制剂中药物从结晶态转变为无定形态。释放模式为双相，开始为突释（12小时内释放64.67±1.53%），随后在48小时内持续释放，从而实现NAC的长期补充。肺部沉积研究表明，包衣的NAC-PLGA-MPPs在发射剂量（86.67±2.52%）、质量中值空气动力学直径（MMAD）值（2.57±0.12微米）、几何标准差（GSD）值（1.55±0.11微米）以及肺部沉积和靶向的肺部细颗粒物分数（FPF）为62.67±2.08%方面显示出良好的结果。最后，药效学研究表明，与NAC相比，NAC-PLGA-MPPs对H37Rv菌株具有更显著的抗菌活性。因此，基于PLGA的颗粒可能是将NAC递送至肺部的更好策略。
