Kushwaha Kalpana, Dwivedi Harinath
School of Pharmacy, BBD University, Lucknow (UP), India.
Pharm Nanotechnol. 2018;6(3):209-217. doi: 10.2174/2211738506666180625120038.
Tuberculosis (TB) is one of the major health challenge in the world. The current treatment of TB needs daily administration of combined drug therapy for six or more months. Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance, as a result, high dose requirement and subsequent intolerable toxicity are seen. Therefore, nanotechnology gained special attention as it has potential to improve patient compliance, bioavailability and reduction in dosing frequency.
The aim of this study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under appropriate conditions using ionic gelation method. The use of natural polymers in nanoparticle fabrication has a vast application due to their biodegradability, biocompatibility and nontoxic nature. Ionic gelation method involves the interaction between macromolecules with opposite charged ionizable groups forming polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased sustained release nano-particulate matrix to improve patient adherence, reducing dose frequency and drug toxicity.
The formulations were based on 32 factorial designs. Nanoparticles of combined drug (Isoniazid- INH and Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process involved the use of pregelated sodium alginate followed by ionic gelation with chitosan. Pregelation of sodium alginate included calcium chloride. The effects of sodium alginate concentration and chitosan concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied.
Optimized Batch-3s showed particle size 539.7 ± 2.33 nm, zeta potential -26.4 ± 0.55 mV, and entrapment efficiency is 70.21 ± 0.24% and 73.45 ± 0.21% of INH and PYZ, respectively. Dissolution release study of Batch-3s in 7.4 pH phosphate buffer exhibited the initial burst of 5.04 ±0.45% and 19.68 ± 0.87% at 0.25 hrs followed by slow, sustained release of drug 74.53 ± 2.53 and 57.87 ± 2.04% at 10 hrs of INH and PYZ, respectively.
It concluded that chitosan (CS) and sodium alginate (AL) concentration are rate-limiting factors in formulation development. Natural polymer based combined drug nano-particulate system could be an innovative and optimistic approach in the treatment of TB.
结核病是全球主要的健康挑战之一。目前的结核病治疗需要每天联合使用药物治疗六个月或更长时间。有时，当前治疗方法的不依从性和较低的生物利用度会导致多药耐药性，结果是出现高剂量需求以及随后难以忍受的毒性。因此，纳米技术受到了特别关注，因为它有潜力提高患者的依从性、生物利用度并降低给药频率。
本研究的目的是使用离子凝胶法在适当条件下制备海藻酸钠-壳聚糖纳米颗粒（AL-CS NPs）。在纳米颗粒制备中使用天然聚合物因其具有生物可降解性、生物相容性和无毒性质而有广泛应用。离子凝胶法涉及带相反电荷的可电离基团的大分子之间相互作用形成聚电解质复合物。因此，合理地配制基于天然聚合物的缓释纳米颗粒基质以提高患者依从性、降低给药频率和药物毒性。
制剂基于32析因设计。使用天然聚合物制备联合药物（异烟肼-INH和吡嗪酰胺-PYZ）的纳米颗粒。制剂过程包括使用预凝胶化的海藻酸钠，然后与壳聚糖进行离子凝胶化。海藻酸钠的预凝胶化包括氯化钙。研究了海藻酸钠浓度和壳聚糖浓度对粒径、zeta电位、包封率和体外药物释放的影响。
优化后的批次3s显示粒径为539.7±2.33nm，zeta电位为-26.4±0.55mV，INH和PYZ的包封率分别为70.21±0.24%和73.45±0.21%。批次3s在pH7.4的磷酸盐缓冲液中的溶出释放研究显示，在0.25小时时初始突释分别为5.04±0.45%和19.68±0.87%，随后在10小时时INH和PYZ分别缓慢、持续释放74.53±2.53%和57.87±2.0/4%。
得出结论，壳聚糖（CS）和海藻酸钠（AL）的浓度是制剂开发中的限速因素。基于天然聚合物的联合药物纳米颗粒系统可能是治疗结核病的一种创新且乐观的方法。
