Fiaschini Noemi, Hanieh Patrizia Nadia, Ariaudo Daniela, Cimino Rita, Abbate Carlo, Romano Elena, Cavalieri Francesca, Venanzi Mariano, Palumbo Valeria, Scimeca Manuel, Bernardini Roberta, Mattei Maurizio, Migliore Alberto, Rinaldi Antonio
Nanofaber S.r.l., Via Anguillarese 301, 00123 Rome, Italy.
Department of Chemical Science and Technologies, University of Rome Tor Vergata, Via Della Ricerca Scientifica 1, 00133 Rome, Italy.
Pharmaceutics. 2024 Dec 13;16(12):1593. doi: 10.3390/pharmaceutics16121593.
BACKGROUND/OBJECTIVES: This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation and damage, while MTX is a common disease-modifying antirheumatic drug (DMARD), the conventional use of which is limited by adverse effects and the lack of release control.
MSP were synthesized as freeze-dried powder to increase their stability and allow for a facile reconstitution prior to administration and precise MTX dosing.
A highly stable and rounded-shaped micrometric MSP, characterized by an open porosity inner structure, achieved both a high MTX loading efficiency and a slow release of MTX after injection. Our drug release assays indeed demonstrated a characteristic drug release profile consisting of a very limited burst release in the first few hours, followed by a slow release of MTX sustained for over a month. By means of a preclinical rat model of RA, the administration of MTX-loaded MSP proved to nearly double the therapeutic efficacy compared to sole MTX, according to a steep reduction in arthritic score compared to control groups. The preclinical study was replicated twice to confirm this improvement in performance and the safety profile of the MSP.
This study suggests that the MSP drug delivery platform holds significant potential for clinical use in improving RA therapy by enabling the sustained slow release of MTX, thereby enhancing therapeutic outcomes and minimizing side effects associated with conventional burst-release drug administration.
背景/目的：本研究旨在开发一种基于透明质酸微球（MSP）的新型纳米技术缓释药物递送平台，用于皮下注射甲氨蝶呤（MTX）以治疗类风湿性关节炎（RA）。RA是一种以关节炎症和损伤为特征的慢性自身免疫性疾病，而MTX是一种常用的改善病情抗风湿药（DMARD），其常规使用受到副作用和缺乏释放控制的限制。
将MSP合成为冻干粉末，以提高其稳定性，并便于在给药前重新配制以及精确的MTX给药剂量。
一种高度稳定且呈圆形的微米级MSP，其特征在于具有开放孔隙的内部结构，注射后实现了高MTX负载效率和MTX的缓慢释放。我们的药物释放试验确实证明了一种特征性的药物释放曲线，包括在最初几个小时内非常有限的突释，随后是持续一个多月的MTX缓慢释放。通过RA的临床前大鼠模型，与单独使用MTX相比，负载MTX的MSP给药证明治疗效果几乎提高了一倍，与对照组相比关节炎评分急剧降低。临床前研究重复进行了两次，以确认MSP在性能和安全性方面的这种改善。
本研究表明，MSP药物递送平台通过实现MTX的持续缓慢释放，在改善RA治疗的临床应用中具有巨大潜力，从而提高治疗效果并最大限度地减少与传统突释药物给药相关的副作用。
