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使用骨关节炎模型评估载有树皮提取物的可注射纤维药物递送系统的临床前方法。

Preclinical approaches to evaluate bark extract loaded FDOFs using osteoarthritis models.

作者信息

Sowjanya Juluru Naga, Raja Rao Proddoku

机构信息

Pharmacy Department, Osmania University, Hyderabad, Telangana, 500007, India.

出版信息

Heliyon. 2024 Oct 2;10(19):e38813. doi: 10.1016/j.heliyon.2024.e38813. eCollection 2024 Oct 15.

DOI:10.1016/j.heliyon.2024.e38813
PMID:39430457
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11489346/
Abstract

Osteoarthritis (OA) is one of the biggest global health issues, affecting two thirds of the population and cannot be fully treated to return normal function or relieve joint discomfort. Oral fast-dissolving films offer a high medication loading capacity, targeted distribution, and increasing bioavailability. The current research explores the in vitro and in vivo efficacy of oral fast-dissolving film formulations containing bark extract. A three-dimensional osteoarthritis (OA) model was created for in vitro assessment using first passage chrondrocytes cultured in a 1:1:3 ratio on trypsin-EDTA medium. C20A4 chondrocytes were cultured on agarose gel at 25± 5 °C in a phosphate buffer solution to create the OA agarose model. One milliliter of RPMI-1640 (10 % FBS) was used for chrondrocyte cultivation. On the third day of incubation, a 20 % (IL-1β) solution was applied, and the media was periodically changed. On the fifth day of incubation, the treated cell line received 5 μL of 0.5 % MTT reagent, and absorbance was examined at 570 nm. The effects of FDOFs on the cell lines were examined for 7, 13, 27, and 35 days (IL-1β, F5, F13 treated IL-1β injected types and Control). As a control, chondrocytes in agarose constructs were solely grown in RPMI-FBS medium without IL-1β. The arthritic effect of improved FDOFs, i.e., F5, was investigated using the GAG, HYP, and DNA quantitation assays in conjunction with a DNA content assay. Monoiodoacetate (MIA) produced arthritis models are well-established for understanding weight bearing and reaction to tactile stimuli in invivo research. Seven-week-old male wistar rats were used in the technique, with celecoxib serving as the positive control and MIA as the negative control. Estimates of osteoarthritic potential were made based on the evaluation of knee thickness and discomfort. The study's findings demonstrated the effectiveness of the F5 formulation on OA models, which need for a clinical evaluation in human beings.

摘要

骨关节炎(OA)是全球最大的健康问题之一,影响着三分之二的人口,且无法得到完全治疗以恢复正常功能或缓解关节不适。口腔速溶膜具有高药物负载能力、靶向分布和提高生物利用度的特点。当前研究探索了含树皮提取物的口腔速溶膜制剂的体外和体内疗效。使用在胰蛋白酶 - 乙二胺四乙酸(EDTA)培养基中按1:1:3比例培养的第一代软骨细胞创建三维骨关节炎(OA)模型用于体外评估。将C20A4软骨细胞在25±5°C的磷酸盐缓冲溶液中的琼脂糖凝胶上培养以创建OA琼脂糖模型。使用1毫升RPMI - 1640(10%胎牛血清)培养软骨细胞。在培养的第三天,施加20%(白细胞介素 - 1β,IL - 1β)溶液,并定期更换培养基。在培养的第五天,处理后的细胞系接受5微升0.5%的噻唑蓝(MTT)试剂,并在570纳米处检测吸光度。在7、13、27和35天检查口腔速溶膜(FDOFs)对细胞系的影响(IL - 1β、F5、F13处理的IL - 1β注射类型和对照)。作为对照,琼脂糖构建体中的软骨细胞仅在不含IL - 1β的RPMI - 胎牛血清培养基中生长。使用糖胺聚糖(GAG)、羟脯氨酸(HYP)和DNA定量测定法以及DNA含量测定法研究改良的口腔速溶膜即F5的关节炎效应。单碘乙酸盐(MIA)诱导的关节炎模型在体内研究中已被充分确立用于理解负重和对触觉刺激的反应。该技术使用7周龄雄性Wistar大鼠,塞来昔布作为阳性对照,MIA作为阴性对照。基于对膝关节厚度和不适的评估对骨关节炎潜力进行估计。该研究结果证明了F5制剂对OA模型的有效性,这需要在人类中进行临床评估。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/cc27fa1b2e83/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/401dfab46d84/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/91e285924db2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/005e6e3b0945/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/676a1f2f8d86/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/ecf8c221a339/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/cc27fa1b2e83/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/401dfab46d84/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/91e285924db2/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/005e6e3b0945/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/676a1f2f8d86/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/ecf8c221a339/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/58db/11489346/cc27fa1b2e83/gr6.jpg

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