Bijukumar Divya, Choonara Yahya E, Murugan Karmani, Choonara Bibi Fatima, Kumar Pradeep, du Toit Lisa C, Pillay Viness
Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
AAPS PharmSciTech. 2016 Oct;17(5):1075-85. doi: 10.1208/s12249-015-0434-6. Epub 2015 Oct 30.
The most successful treatment strategy for arthritis is intra-articular injections that are costly and have reduced patient compliance. The purpose of the current study was to develop an inflammation-sensitive system for topical drug administration. Multi-macromolecular alginate-hyaluronic acid-chitosan (A-H-C) polyelectrolyte complex nanoparticles, loaded with indomethacin were developed employing pre-gel and post-gel techniques in the presence of dodecyl-L-pyroglutamate (DLP). In addition to in vitro studies, in silico simulations were performed to affirm and associate the molecular interactions inherent to the formulation of core all-natural multi-component biopolymeric architectures composed of an anionic (alginate), a cationic (chitosan), and an amphi-ionic polyelectrolytic (hyaluronic acid) macromolecule. The results demonstrated that DLP significantly influenced the size of the synthesized nanoparticles. Drug-content analysis revealed higher encapsulation efficiency (77.3%) in the presence of DLP, irrespective of the techniques used. Moreover, in vitro drug release studies showed that indomethacin release from the nanosystem was significantly improved (98%) in Fenton's reagent. Drug permeation across a cellulose membrane using a Franz diffusion cell system showed an initial surge flux (0.125 mg/cm(-2)/h), followed by sustained release of indomethacin for the post-gel nanoparticles revealing its effective skin permeation efficiency. In conclusion, the study presents novel nanoparticles which could effectively encapsulate and deliver hydrophobic drugs to the target site, particularly for arthritis.
治疗关节炎最成功的策略是关节内注射，但这种方法成本高昂且患者依从性较低。本研究的目的是开发一种用于局部给药的炎症敏感系统。采用预凝胶和后凝胶技术，在十二烷基-L-焦谷氨酸（DLP）存在的情况下，制备了负载吲哚美辛的多聚电解质复合纳米粒，其由多聚大分子海藻酸钠-透明质酸-壳聚糖（A-H-C）组成。除了体外研究，还进行了计算机模拟，以确认和关联由阴离子（海藻酸钠）、阳离子（壳聚糖）和两性离子聚电解质（透明质酸）大分子组成的核心全天然多组分生物聚合物结构制剂中固有的分子相互作用。结果表明，DLP对合成纳米粒的尺寸有显著影响。药物含量分析显示，无论采用何种技术，在DLP存在的情况下，包封率都更高（77.3%）。此外，体外药物释放研究表明，在芬顿试剂中，纳米系统中吲哚美辛的释放显著提高（98%）。使用弗兰兹扩散池系统进行的药物透过纤维素膜的研究显示，初始涌动通量为（0.125 mg/cm(-2)/h），随后后凝胶纳米粒中的吲哚美辛持续释放，表明其具有有效的皮肤渗透效率。总之，该研究提出了一种新型纳米粒，它可以有效地将疏水性药物包裹并递送至靶部位，特别是用于治疗关节炎。
