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Sesamol-Loaded PLGA Nanosuspension for Accelerating Wound Healing in Diabetic Foot Ulcer in Rats
International Journal of Nanomedicine ( IF 8 ) Pub Date : 2020-11-23 , DOI: 10.2147/ijn.s268941
Karthik Gourishetti 1 , Raghuvir Keni 1 , Pawan Ganesh Nayak 1 , Srinivas Reddy Jitta 2 , Navya Ajitkumar Bhaskaran 2 , Lalit Kumar 2 , Nitesh Kumar 1 , Nandakumar Krishnadas 1 , Rekha Raghuveer Shenoy 1
Affiliation  

Background: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition.
Methods: Sesamol-PLGA (SM-PLGA) nanosuspension was developed using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson’s trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections.
Results: The optimized SM-PLGA nanosuspension had an average particle size of < 300 nm, PDI< 0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels’ development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed.
Conclusion: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.



中文翻译:

芝麻酚负载 PLGA 纳米混悬剂加速大鼠糖尿病足溃疡伤口愈合

背景:糖尿病足溃疡是糖尿病的一种难治性并发症,其特点是伤口愈合的炎症和增殖阶段受到干扰。芝麻酚是一种酚类化合物,以其强大的抗氧化、抗炎、抗高血糖和伤口愈合特性而闻名。本研究的目的是开发芝麻酚纳米制剂,并研究其对糖尿病足部伤口愈合过程各个阶段的影响。
方法:Sesamol-PLGA (SM-PLGA) 纳米混悬剂是使用纳米沉淀法开发的。对优化的配方进行了 TEM、体外药物释放试验和体内药代动力学研究。使用高脂肪饮食 (HFD) 喂养的链脲佐菌素诱导的 II 型糖尿病动物模型中的糖尿病足溃疡 (DFU) 来评估 SM-PLGA 纳米混悬剂的功效。SM-PLGA纳米混悬剂通过口服途径给药。使用 ELISA 估计 TNF-α 水平,并进行蛋白质印迹分析以评估对伤口组织中 HSP-27、ERK、PDGF-B 和 VEGF 表达的影响。通过 H&E 和 Masson 三色染色评估伤口再上皮化、成纤维细胞迁移、胶原沉积和炎性细胞浸润。通过伤口切片中的 CD-31 IHC 染色评估对血管生成的影响。
结果:优化的 SM-PLGA 纳米混悬剂的平均粒径 < 300 nm,PDI < 0.200,具有球形颗粒。在体外试验中,大约 80% 的药物在 60 小时内释放。发现该制剂的半衰期为 13.947 ± 0.596 小时。SM-PLGA 纳米混悬剂治疗降低了伤口组织中的 TNF-α 水平并加速了胶原蛋白的沉积。而 HSP-27、ERK、PDGF-B 和 VEGF 的表达增加并改善了新血管的发育。还观察到伤口部位的快速上皮再形成、成纤维细胞迁移、胶原沉积和炎症细胞浸润减少。
结论:结果表明,芝麻酚-PLGA 纳米混悬剂通过恢复糖尿病患者改变的伤口愈​​合过程,显着促进糖尿病足溃疡的伤口愈合。

更新日期:2020-11-23
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