Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model.
Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model.
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DOI：
10.1080/10717544.2023.2184307
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发表时间：
2023-12
期刊：
影响因子：
6
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中科院分区：
文献类型：
--
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风湿性关节炎（RA）是一种严重影响患者生活质量的全身性自身免疫性疾病。鉴于RA的病理生理学的复杂性，没有单一的治疗可以完全阻止疾病的进展。在这里，我们试图通过使用海藻酸钠（SA）-普朗尼克F127（PF-127）原位水凝胶制剂，共同递送甲氨蝶呤（MTX）（一种标准的慢作用抗风湿药物）和异硫氰酸苯乙酯（PEITC）（一种生物活性植物化学物质）来整体和协同治疗RA。因此，在当前的研究中，MTX和PEITC以纳米颗粒形式的共递送可以帮助增强稳定性和溶解度，并促进在靶关节炎组织中的更大渗透。发现所制造的MTX NP和PEITC NE具有最小粒径、PDI和良好的ζ电位。体外释放研究结果表明，MTX和PEITC通过扩散和侵蚀机制在6-7天内从DD NP HG基质中同时释放。DD NP HG关节内（IA）注射显著减少了佐剂诱导的关节炎（AIA）大鼠的慢性炎症，延迟了骨侵蚀的发作，显著减少了滑膜炎，并且下调了炎性细胞因子的表达。最值得注意的是，共递送策略几乎完全恢复了RA大鼠踝关节的形态学特征。肝肾功能试验表明，DD NP HG在RA条件下具有良好的生物安全性。综上所述，这些研究结果表明，DD NP HG可以通过MTX和PEITC两种纳米颗粒形式之间的协同作用实现良好的抗炎活性和逆转软骨破坏，这可以有效地改善其游离形式的缺点。成功地构建了纳米结构的双载药智能水凝胶（DD NP HG），用于将MTX和PEITC关节内递送到RA的受影响关节。MTX（MTX NP）和PEITC（PEITC NE）两者的纳米制剂的制造有助于减轻游离形式药物的缺点和药物相关的副作用。DD NP HG能明显抑制关节炎大鼠的关节炎性反应，并对骨破坏有保护作用。PEITC和MTX（DD NP HG）的这种组合方法协同地提高了抗关节炎活性并降低了体内不良副作用。
Rheumatoid arthritis (RA), a systemic autoimmune disease that dramatically affects patients’ quality of life. Given the intricacy of RA’s pathophysiology, no single treatment can completely halt the disease progression. Here, we attempted to treat RA holistically and synergistically by co-delivering methotrexate (MTX), a standard slow-acting anti-rheumatic drug, and phenethyl isothiocyanate (PEITC), a bioactive phytochemical, using a sodium alginate (SA)-pluronic F127 (PF-127) in situ hydrogel formulation. Therefore, in the current study, the co-delivery of MTX and PEITC in the nanoparticulate form could help enhance stability and solubility and facilitate greater penetration in the target arthritic tissues. The fabricated MTX NP and PEITC NE were found to have a minimum particle size, PDI, and good zeta potential. Results from in vitro release studies showed that MTX and PEITC were simultaneously released from the DD NP HG matrix over 6–7 days through diffusion and erosion mechanisms. An intra-articular (IA) injection of DD NP HG dramatically reduced chronic inflammation in adjuvant-induced arthritis (AIA) rats, delayed the onset of bone erosion, significantly reduced synovitis, and down-regulated the inflammatory cytokine expression. Most notably, the co-delivery strategy almost entirely restored the morphological features of the ankle joints of RA rats. The hepatic and renal function tests indicated good biological safety for DD NP HG in RA conditions. Taken together, these findings indicated that DD NP HG could achieve good anti-inflammatory activity and reverse cartilage disruption through a synergistic effect between two nanoparticulate forms of MTX and PEITC, which can effectively improve the drawbacks of their free forms. A nanostructured dual-drug loaded smart hydrogel (DD NP HG) was successfully constructed for the intra-articular delivery of MTX and PEITC to the affected joints of RA. The fabrication of the nanoformulation of both MTX (MTX NP) and PEITC (PEITC NE) aided in mitigating the drawbacks and drug-related side effects of the free form of drugs. DD NP HG markedly suppressed joint inflammation and protect against bone destruction in arthritic rats. This combination approach of PEITC and MTX (DD NP HG) synergistically improved anti-arthritic activity and reduced the adverse side effects in vivo.
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使用基于 D-氨基酸的超分子水凝胶治疗类风湿性关节炎具有强大的药物生物利用度和安全性。
影响因子：
8.2
作者：
Ma, Shaodan;Gu, Shunan;Zhang, Jinwei;Qi, Weizhong;Lin, Zhaowei;Zhai, Weicheng;Zhan, Jie;Li, Qi;Cai, Yanbin;Lu, Yao
通讯作者：
Lu, Yao
影响因子：
10.9
作者：
Cang S;Ma Y;Chiao JW;Liu D
通讯作者：
Liu D
影响因子：
--
作者：
Aborehab NM;El Bishbishy MH;Refaiy A;Waly NE
通讯作者：
Waly NE
影响因子：
4.1
作者：
Mohanty S;Sahoo AK;Konkimalla VB;Pal A;Si SC
通讯作者：
Si SC
DOI：
10.2147/dddt.s143942
发表时间：
2017
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Gao L;Xia L;Zhang R;Duan D;Liu X;Xu J;Luo L
通讯作者：
Luo L