Synergistically engineered nanotransethosomes for co-delivery of methotrexate and baicalin for enhanced transdermal delivery against rheumatoid arthritis: Formulation, characterization, and invivo pharmacodynamic evaluation.

IF 4.3 4区医学 Q1 PHARMACOLOGY & PHARMACY

Journal of Drug Targeting Pub Date : 2024-04-23 DOI:10.1080/1061186X.2024.2347371

S. Adin, I. Gupta, M. Aqil, M. Mujeeb, A. Najmi

{"title":"Synergistically engineered nanotransethosomes for co-delivery of methotrexate and baicalin for enhanced transdermal delivery against rheumatoid arthritis: Formulation, characterization, and invivo pharmacodynamic evaluation.","authors":"S. Adin, I. Gupta, M. Aqil, M. Mujeeb, A. Najmi","doi":"10.1080/1061186X.2024.2347371","DOIUrl":null,"url":null,"abstract":"Rheumatoid arthritis (RA) is a systemic autoimmune disease that significantly impacts the quality of life of those affected. Owing to the complex pathophysiology of RA, it is not possible for any singular treatment to entirely impede the progression of the disease. Hence, the current study aimed to adopt a holistic and synergistic approach towards the management of RA by means of a co-delivery strategy involving methotrexate (MTH), a conventional slow-acting anti-rheumatic drug, and baicalin (BCN), a bioactive phytochemical using a transethosomal (TRS) gel formulation. The present study aims to evaluate the potential benefits of administering MTH and BCN in nanoparticulate form, which may lead to improved stability and solubility, as well as enhanced penetration into the arthritic tissues of interest. The MTH-BCN-TRS that were synthesised exhibited small particle size of 151.3 nm and polydispersity index of 0.125, as well as a favourable zeta potential of -32.22 mV. Additional assessments were conducted, including a pharmacokinetic analysis, TEM, skin permeation analysis, and confocal microscopy. According to the Confocal laser scanning microscopy (CLSM) study, the formulated MTH-BCN-TRS gel exhibited superior MTH and BCN permeation through the skin layers when compared to the MTH-BCN suspension gel. The MTT experiment on Raw 264.7 and SW982 cell lines revealed a considerable reduction (P < 0.05) in the IC50 value of the MTH-BCN-TRS formulation (9.2 mM and 43.2 mM, respectively) in comparison to the drug suspension. According to the findings of the in vivo study, it was found that the MTH-BCN-TRS gel exhibits significantly promising anti-arthritic properties when compared to the conventional diclofenac gel. This was demonstrated through histopathological studies and radiographic analysis. Furthermore, skin irritation investigation on Wistar albino rats confirmed that the formulated MTH-BCN-TRS is a safe option for topical treatment on the skin. The present study has confirmed that the formulated TRS vesicles are a valuable carrier for the transdermal delivery of MTH and BCN, which may be used for the management of rheumatoid arthritis.","PeriodicalId":15573,"journal":{"name":"Journal of Drug Targeting","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Drug Targeting","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/1061186X.2024.2347371","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease that significantly impacts the quality of life of those affected. Owing to the complex pathophysiology of RA, it is not possible for any singular treatment to entirely impede the progression of the disease. Hence, the current study aimed to adopt a holistic and synergistic approach towards the management of RA by means of a co-delivery strategy involving methotrexate (MTH), a conventional slow-acting anti-rheumatic drug, and baicalin (BCN), a bioactive phytochemical using a transethosomal (TRS) gel formulation. The present study aims to evaluate the potential benefits of administering MTH and BCN in nanoparticulate form, which may lead to improved stability and solubility, as well as enhanced penetration into the arthritic tissues of interest. The MTH-BCN-TRS that were synthesised exhibited small particle size of 151.3 nm and polydispersity index of 0.125, as well as a favourable zeta potential of -32.22 mV. Additional assessments were conducted, including a pharmacokinetic analysis, TEM, skin permeation analysis, and confocal microscopy. According to the Confocal laser scanning microscopy (CLSM) study, the formulated MTH-BCN-TRS gel exhibited superior MTH and BCN permeation through the skin layers when compared to the MTH-BCN suspension gel. The MTT experiment on Raw 264.7 and SW982 cell lines revealed a considerable reduction (P < 0.05) in the IC50 value of the MTH-BCN-TRS formulation (9.2 mM and 43.2 mM, respectively) in comparison to the drug suspension. According to the findings of the in vivo study, it was found that the MTH-BCN-TRS gel exhibits significantly promising anti-arthritic properties when compared to the conventional diclofenac gel. This was demonstrated through histopathological studies and radiographic analysis. Furthermore, skin irritation investigation on Wistar albino rats confirmed that the formulated MTH-BCN-TRS is a safe option for topical treatment on the skin. The present study has confirmed that the formulated TRS vesicles are a valuable carrier for the transdermal delivery of MTH and BCN, which may be used for the management of rheumatoid arthritis.

查看原文本刊更多论文

甲氨蝶呤和黄芩苷联合给药的协同工程纳米透硫体用于增强类风湿性关节炎的透皮给药：配方、表征和体内药效学评估。

类风湿性关节炎（RA）是一种系统性自身免疫疾病，严重影响患者的生活质量。由于类风湿性关节炎的病理生理学十分复杂，任何单一的治疗方法都不可能完全阻止疾病的发展。因此，本研究旨在采用一种整体和协同的方法来治疗 RA，即采用一种联合给药策略，将传统的慢作用抗风湿药物甲氨蝶呤（MTH）和具有生物活性的植物化学物质黄芩苷（BCN）用经血脑屏障（TRS）凝胶制剂联合给药。本研究旨在评估以纳米颗粒形式给药 MTH 和 BCN 的潜在益处，这可能会提高稳定性和溶解度，并增强对相关关节炎组织的渗透。合成的 MTH-BCN-TRS 粒径小，为 151.3 nm，多分散指数为 0.125，Zeta 电位为 -32.22 mV。还进行了其他评估，包括药代动力学分析、TEM、皮肤渗透分析和共聚焦显微镜。根据共聚焦激光扫描显微镜（CLSM）研究，与 MTH-BCN 悬浮凝胶相比，配制的 MTH-BCN-TRS 凝胶在皮肤层中的 MTH 和 BCN 渗透率更高。对 Raw 264.7 和 SW982 细胞系进行的 MTT 实验显示，与药物悬浮液相比，MTH-BCN-TRS 配方的 IC50 值（分别为 9.2 mM 和 43.2 mM）大幅降低（P < 0.05）。体内研究结果表明，与传统的双氯芬酸凝胶相比，MTH-BCN-TRS 凝胶具有明显的抗关节炎特性。这一点已通过组织病理学研究和放射学分析得到证实。此外，对 Wistar 白化大鼠进行的皮肤刺激调查证实，配制的 MTH-BCN-TRS 是一种安全的皮肤局部治疗选择。本研究证实，配制的 TRS 囊泡是透皮给药 MTH 和 BCN 的重要载体，可用于治疗类风湿性关节炎。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Drug Targeting 医学-药学

CiteScore

9.10

自引率

0.00%

发文量

165

审稿时长

2 months

期刊介绍： Journal of Drug Targeting publishes papers and reviews on all aspects of drug delivery and targeting for molecular and macromolecular drugs including the design and characterization of carrier systems (whether colloidal, protein or polymeric) for both vitro and/or in vivo applications of these drugs. Papers are not restricted to drugs delivered by way of a carrier, but also include studies on molecular and macromolecular drugs that are designed to target specific cellular or extra-cellular molecules. As such the journal publishes results on the activity, delivery and targeting of therapeutic peptides/proteins and nucleic acids including genes/plasmid DNA, gene silencing nucleic acids (e.g. small interfering (si)RNA, antisense oligonucleotides, ribozymes, DNAzymes), as well as aptamers, mononucleotides and monoclonal antibodies and their conjugates. The diagnostic application of targeting technologies as well as targeted delivery of diagnostic and imaging agents also fall within the scope of the journal. In addition, papers are sought on self-regulating systems, systems responsive to their environment and to external stimuli and those that can produce programmed, pulsed and otherwise complex delivery patterns.