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设计并将肽-共聚物缀合物自组装成纳米颗粒水凝胶,用于糖尿病伤口愈合。

Design and Self-Assembly of Peptide-Copolymer Conjugates into Nanoparticle Hydrogel for Wound Healing in Diabetes.

机构信息

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

The Innovation Team for Integrating Pharmacy with Entrepreneurship, Guangdong Pharmaceutical University, Guangzhou, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Mar 9;19:2487-2506. doi: 10.2147/IJN.S452915. eCollection 2024.

DOI:10.2147/IJN.S452915
PMID:38486937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10938256/
Abstract

BACKGROUND

Delayed wound healing in skin injuries has become a significant problem in clinics, seriously affecting and even threatening life and health. Recently, research interest has increased in developing wound dressings containing bioactive compounds capable of improving outcomes for complex healing needs.

METHODS

In this study, -loaded nanoparticles (Pue-NPs) were prepared using the cell-penetrating peptide-poly (lactic-co-glycolic acid) (CPP-PLGA) as a drug carrier by the emulsified solvent evaporation method. Then, they were added into poly (acrylic acid) to obtain a self-assembled nanocomposite hydrogels (SANHs) drug delivery system using the co-polymerization method. The particle size, zeta potential, and micromorphology of Pue-NPs were measured; the appearance, mechanical properties, adhesive strength, and biological activity of SANHs were performed. Finally, the potential of SANHs for wound healing was further evaluated in streptozotocin-induced diabetic mice.

RESULTS

Pue-NPs were regularly spherical, with an average particle size of 134.57 ± 1.42 nm and a zeta potential of 2.14 ± 0.78 mV. SANHs was colorless and transparent with a honeycomb-like porous structure and had an excellent swelling ratio (917%), water vapor transmission rate (3077 g·m·day), mechanical properties (Young's modulus of 18 kPa, elongation at break of 307%), and adhesive strength (15.5 kPa). SANHs exhibited sustained release of Pue over 48h, with a cumulative release of 55.60 ± 6.01%. In vitro tests revealed that the SANHs presented a 92.22% antibacterial rate against after 4h, and a 61.91% scavenging rate of 1.1-diphenyl-2-trinitrophenylhydrazine (DPPH) radical. In vivo experiments showed that SANHs accelerated wound repair by reducing the inflammatory response at the wound site, promoting angiogenesis, and facilitating epidermal regeneration and collagen deposition.

CONCLUSION

In conclusion, we successfully prepared SANHs. Our results show that SANHs have excellent performance and improves wound healing in diabetic mice model, indicating that it can be used to develop an effective strategy for the treatment of diabetic wounds.

摘要

背景

皮肤损伤的延迟愈合已成为临床中的一个重大问题,严重影响甚至威胁生命和健康。最近,人们对开发含有能够改善复杂愈合需求的生物活性化合物的伤口敷料的研究兴趣日益增加。

方法

在这项研究中,采用细胞穿透肽-聚(乳酸-共-乙醇酸)(CPP-PLGA)作为药物载体,通过乳化溶剂蒸发法制备负载紫杉醇的纳米粒子(Pue-NPs)。然后,通过共聚法将其添加到聚丙烯酸中,得到自组装纳米复合水凝胶(SANHs)给药系统。测量了 Pue-NPs 的粒径、Zeta 电位和微观形态;对 SANHs 的外观、力学性能、粘附强度和生物活性进行了研究。最后,在链脲佐菌素诱导的糖尿病小鼠中进一步评价了 SANHs 促进伤口愈合的潜力。

结果

Pue-NPs 呈规则球形,平均粒径为 134.57±1.42nm,Zeta 电位为 2.14±0.78mV。SANHs 呈无色透明状,具有蜂窝状多孔结构,具有优异的溶胀比(917%)、水蒸气透过率(3077g·m·day)、力学性能(杨氏模量 18kPa,断裂伸长率 307%)和粘附强度(15.5kPa)。SANHs 可在 48h 内持续释放 Pue,累积释放率为 55.60±6.01%。体外试验表明,SANHs 对金黄色葡萄球菌的抑菌率在 4h 时达到 92.22%,对 1.1-二苯基-2-三硝基苯肼(DPPH)自由基的清除率达到 61.91%。体内实验表明,SANHs 通过减少伤口部位的炎症反应、促进血管生成以及促进表皮再生和胶原沉积,加速伤口修复。

结论

综上所述,我们成功制备了 SANHs。研究结果表明,SANHs 具有优异的性能,可促进糖尿病小鼠模型的伤口愈合,表明其可用于开发治疗糖尿病伤口的有效策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/9295170d5d8f/IJN-19-2487-g0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/246ab9258499/IJN-19-2487-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/81384a34ee58/IJN-19-2487-g0007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/246ab9258499/IJN-19-2487-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/41515626dd8d/IJN-19-2487-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/16681356f67a/IJN-19-2487-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/b688d334d447/IJN-19-2487-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/b5175d1d34dd/IJN-19-2487-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/81384a34ee58/IJN-19-2487-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/193d/10938256/a1c1f73a4c63/IJN-19-2487-g0008.jpg
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