Formulation optimization and biodistribution of epigallocatechin gallate phospholipid complex-loaded NLCs for rheumatoid arthritis treatment

Rheumatoid arthritis (RA) is a chronic autoimmune disorder that undergoes joint pain inflammation and stiffness. Current treatments associated with severe side effects and high costs. Alternative treatment, that is, Epigallocatechin gallate (EGCG) a green tea polyphenol that directly targeted RA inflammatory pathways. But it has bitter taste, poor bioavailability, and toxicity issues. This research aimed to address these limitations through complexation of EGCG with phospholipids (EGCG-PC) and loading it into nanostructured lipid carriers (NLCs). The complexation with phospholipid technique has been shown to be a more successful approach. The solvent evaporation approach has been utilized to manufacture drug complex, which increases the stability and effectiveness of the products. EGCG-PC-NLCs improve solubility, sustained release, and increased bioavailability. The particle size, zeta potential, and PDI of EGCG-PC-NLCs were 159.65 ± 1.34 nm, −21.5 ± 0.99 mV, and 0.148 ± 0.045. It showed sustained drug release in 24 hours where pure EGCG degraded within 4 hours. Anti-rheumatic efficacy was done through <i>in vitro</i> cell viability assays. Toxicity, <i>ex vivo</i>, and <i>in vivo</i> biodistribution studies improved intestinal permeability, exhibited lower toxicity, undergoes lymphatic pathway and avoided rapid clearance. The dual formulation of EGCG phospholipid complex and NLCs showed a safer therapeutic option for RA treatment.

类风湿关节炎（Rheumatoid arthritis, RA）是一种以关节疼痛、炎症及僵硬为主要表现的慢性自身免疫性疾病。当前临床治疗手段多伴随严重不良反应与高昂成本。表没食子儿茶素没食子酸酯（Epigallocatechin gallate, EGCG）作为一种绿茶多酚类物质，可直接靶向RA的炎症通路，是潜在的替代治疗方案。但该物质存在口感苦涩、生物利用度低以及潜在毒性等缺陷。本研究通过将EGCG与磷脂复合（EGCG-PC）并载入纳米结构脂质载体（nanostructured lipid carriers, NLCs），以期解决上述局限。磷脂复合技术已被证实为更为有效的改性手段，本研究采用溶剂蒸发法制备该药物复合物，可有效提升制剂的稳定性与药效。EGCG-PC-NLCs可显著提升药物溶解度、实现长效缓释并提高生物利用度。EGCG-PC-NLCs的粒径、zeta电位及多分散性指数（polydispersity index, PDI）分别为159.65±1.34 nm、-21.5±0.99 mV及0.148±0.045。该制剂可实现24小时长效药物缓释，而游离EGCG仅在4小时内即发生降解。抗类风湿药效通过体外（in vitro）细胞活力实验进行评估。毒性、离体（ex vivo）及体内（in vivo）生物分布研究结果显示，该制剂可提升肠道通透性、降低毒性、经由淋巴通路递送并避免快速清除。综上，EGCG磷脂复合物联合纳米结构脂质载体的双重制剂，为RA治疗提供了更为安全的治疗选择。