Narisepalli Saibhargav, Salunkhe Shubham A, Chitkara Deepak, Mittal Anupama
Department of Pharmacy, Birla Institute of Technology and Science (BITS PILANI), Pilani, Rajasthan, 333031, India.
Macromol Biosci. 2025 Feb;25(2):e2400406. doi: 10.1002/mabi.202400406. Epub 2024 Nov 27.
Neurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 - 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 - 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.
神经降压素（NT）是一种生物活性十三肽，通过调节炎症和血管生成来促进糖尿病伤口愈合。然而，它在富含肽酶的伤口环境中迅速降解（血浆半衰期<2分钟），限制了其疗效。为了解决这个问题，开发了神经降压素共轭聚合物多孔微粒（NT-PMP），并将其负载在明胶（15% w/v水凝胶）中用于局部应用，实现NT的持续释放以提高治疗效果。NT-PMP的尺寸范围为60 - 240 µm（平均：120.63 ± 40.71 µm），孔径为5 - 16 µm（平均：10.68 ± 3.47 µm）。体外研究表明NT-PMP在成纤维细胞中具有细胞相容性，并降低了炎症诱导的巨噬细胞中的TNF-α水平（1256 ± 167.02 pg/ml）。进一步的NT-PMP支架在将真皮成纤维细胞接种到PMP表面时表现出优异的细胞粘附和迁移特性。在糖尿病伤口大鼠模型中的体内研究表明，NT-PMP能够有效管理伤口，其特征是在存在NT-PMP的情况下具有显著的再生和愈合特性。这包括完全重新上皮化、降低促炎细胞因子（TNF-α）以及增强VEGF表达，最终在应用NT-PMP凝胶后导致糖尿病伤口中形成组织良好的胶原基质。总之，负载在水凝胶中的NT共轭PMP表现出显著的再生和愈合特性，表明其作为糖尿病伤口替代治疗方法的潜力。
