Osteoarthritis (OA) is a complex multi-target disease with an unmet medical need for the development of therapies that slow and potentially revert disease progression. Intra-articular (IA) delivery has seen a surge in osteoarthritis research in recent years. As local administration of molecules, this represents a way to circumvent systemic drug delivery struggles. When developing intra-articular formulations, the main goals are a sustained and controlled release of therapeutic drug doses, taking into account carrier choice, drug molecule, and articular joint tissue target. Therefore, the selection of models is critical when developing local administration formulation in terms of accurate outcome assessment, target and off-target effects and relevant translation to in vivo. The current review highlights the applications of OA in vitro models in the development of IA formulation by means of exploring their advantages and disadvantages. In vitro models are essential in studies of OA molecular pathways, understanding drug and target interactions, assessing cytotoxicity of carriers and drug molecules, and predicting in vivo behaviors. However, further understanding of molecular and tissue-specific intricacies of cellular models for 2D and 3D needs improvement to accurately portray in vivo conditions.

中文翻译：

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骨关节炎体外模型：关节内药物递送系统开发中的应用和意义

骨关节炎（OA）是一种复杂的多目标疾病，对开发能够减缓并可能逆转疾病进展的疗法的医疗需求尚未得到满足。近年来，关节内（IA）输送已引起骨关节炎研究的激增。作为分子的局部给药，这代表了一种避免全身性药物输送斗争的方法。在开发关节内制剂时，主要目标是考虑到载体选择，药物分子和关节联合组织靶点，持续和控制释放治疗药物剂量。因此，从准确的结果评估，靶标和脱靶效应以及体内相关翻译的角度出发，开发局部给药制剂时，模型的选择至关重要。本综述通过探讨它们的优缺点，重点介绍了OA体外模型在IA制剂开发中的应用。体外模型对于OA分子途径的研究，了解药物和靶标的相互作用，评估载体和药物分子的细胞毒性以及预测体内行为至关重要。但是，需要进一步了解2D和3D细胞模型的分子和组织特定的复杂性，才能准确地描述体内状况。