Koland Marina, Narayanan Vadakkepushpakath Anoop, John Anish, Tharamelveliyil Rajendran Arunraj, Raghunath Indu
Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (Deemed to be University), Mangalore 575018, India.
Gels. 2022 Nov 8;8(11):723. doi: 10.3390/gels8110723.
The intra-articular administration of conventional drug solutions or dispersions in joint diseases such as osteoarthritis has a relatively short retention time and, therefore, limited therapeutic effect. Thermosensitive polymer solutions that exhibit a sol-gel phase transition near body temperature after injection can prolong drug retention by providing a depot from which the drug release is sustained while relieving inflammation and preventing degradation of the joint complex. Thermosensitive hydrogels have in recent times garnered considerable attention in the intra-articular therapeutics of joint diseases such as osteoarthritis. Among the stimuli-responsive gelling systems, most research has focused on thermosensitive hydrogels. These gels are preferred over other stimuli-sensitive hydrogels since they have well-controlled in situ gelling properties and are also easier to load with drugs. Temperature-sensitive polymers, such as block copolymers or poloxamers, are frequently used to modify their gelation properties, usually in combination with other polymers. They are compatible with most drugs but may pose formulation challenges in terms of their low-response time, highly fragile nature, and low biocompatibility. The stability and biodegradability of implant hydrogels can control the drug release rate and treatment efficacy. This review stresses the application of thermosensitive gels in joint disorders and summarizes recent developments for intra-articular application, including the incorporation of nanoparticles. The hydrogel composition, drug release mechanisms, and the challenges involved in their formulation and storage are also discussed.
在骨关节炎等关节疾病中，关节腔内注射常规药物溶液或分散液的保留时间相对较短，因此治疗效果有限。注射后在体温附近呈现溶胶-凝胶相转变的热敏聚合物溶液，可以通过提供一个药物持续释放的储库来延长药物保留时间，同时减轻炎症并防止关节复合体退化。近年来，热敏水凝胶在骨关节炎等关节疾病的关节腔内治疗中受到了相当大的关注。在刺激响应性凝胶系统中，大多数研究都集中在热敏水凝胶上。与其他刺激敏感水凝胶相比，这些凝胶更受青睐，因为它们具有良好控制的原位凝胶化特性，并且也更容易负载药物。温度敏感聚合物，如嵌段共聚物或泊洛沙姆，经常用于改变其凝胶化特性，通常与其他聚合物结合使用。它们与大多数药物兼容，但在低响应时间、高度脆弱的性质和低生物相容性方面可能带来制剂挑战。植入水凝胶的稳定性和生物降解性可以控制药物释放速率和治疗效果。本综述强调了热敏凝胶在关节疾病中的应用，并总结了关节腔内应用的最新进展，包括纳米颗粒的掺入。还讨论了水凝胶组成、药物释放机制以及它们在制剂和储存方面所涉及的挑战。
