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开发协同控释聚合物植入物以控制微创青光眼手术中单抗药物的释放。

Developing a synergistic rate-retarding polymeric implant for controlling monoclonal antibody delivery in minimally invasive glaucoma surgery.

机构信息

Faculty of Life Sciences & Medicine, King's College London, London SE1 1UL, UK.

Faculty of Life Sciences & Medicine, King's College London, London SE1 1UL, UK.

出版信息

Int J Biol Macromol. 2024 Jun;272(Pt 1):132655. doi: 10.1016/j.ijbiomac.2024.132655. Epub 2024 May 24.

DOI:10.1016/j.ijbiomac.2024.132655
PMID:38797299
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11780753/
Abstract

Monoclonal antibodies (mAbs) have garnered substantial attention within the field of ophthalmology and can be used to suppress scar formation after minimally invasive glaucoma surgeries. Here, by controlling mAb passive diffusion, we developed a polymeric, rate-controlling membrane reservoir loaded with poly(lactic-co-glycolic acid) microspheres to deliver mAb for several weeks. Different parameters were tested to ensure that the microspheres achieved a good quality characteristic, and our results showed that 1 %W/V emulsifier with 5 %W/V NaCl achieved mAb-loaded microspheres with the highest stability, encapsulation efficiency and minimal burst release. Then, we fabricated and compared 10 types of microporous films based on polylactic acid (PLA), polycaprolactone (PCL), and polyethylene glycol (PEG). Our results revealed distinct pore characteristics and degradation patterns in different films due to varying polymer properties, and all the polymeric film formulations showed good biocompatibility in both human trabecular meshwork cells and human conjunctival fibroblasts. Finally, the optimized microspheres were loaded into the reservoir-type polymeric implant assembled by microporous membranes with different surface coating modifications. The implant formulation, which was fabricated by 60 PCL: 40 PEG (3 %W/V) polymer with 0.1 %W/V poly(lactic-co-glycolic acid) barrier, exerted the best drug release profile that can sustained release mAb (83.6 %) for 4 weeks.

摘要

单克隆抗体(mAbs)在眼科领域引起了广泛关注,可用于抑制微创青光眼手术后的疤痕形成。在这里,通过控制 mAb 的被动扩散,我们开发了一种聚合物、速率控制的膜储库,其中装载了载有聚(乳酸-共-乙醇酸)微球的聚合物,以在数周内递送 mAb。测试了不同的参数以确保微球具有良好的质量特性,我们的结果表明,含有 1%W/V 乳化剂和 5%W/V NaCl 的微球可实现 mAb 载药微球的最高稳定性、包封效率和最小突释。然后,我们基于聚乳酸(PLA)、聚己内酯(PCL)和聚乙二醇(PEG)制造并比较了 10 种微孔膜。由于聚合物性质的不同,我们的结果揭示了不同薄膜中明显的孔特征和降解模式,所有聚合物膜配方在人眼小梁网细胞和人结膜成纤维细胞中均表现出良好的生物相容性。最后,将优化后的微球载入由具有不同表面涂层修饰的微孔膜组装的储库型聚合物植入物中。该植入物配方由 60%PCL:40%PEG(3%W/V)聚合物和 0.1%W/V 聚(乳酸-共-乙醇酸)阻隔剂组成,表现出最佳的药物释放曲线,可以持续释放 mAb(83.6%)长达 4 周。

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