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透明质酸修饰没食子酸嵌合壳聚糖纳米粒作为一种有效的银屑病治疗给药系统。

Hyaluronic acid engineered gallic acid embedded chitosan nanoparticle as an effective delivery system for treatment of psoriasis.

机构信息

Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India.

School of Pharmacy, Monash University, Bandar Sunway, Jalan Lagoon Selatan, 47500, Malaysia.

出版信息

Environ Res. 2023 Dec 1;238(Pt 1):117086. doi: 10.1016/j.envres.2023.117086. Epub 2023 Sep 6.

DOI:10.1016/j.envres.2023.117086
PMID:37683783
Abstract

Psoriasis is a deleterious auto-immune disorder which seriously harms the patients physical and mental health. CD44 are found to be over-expressed on psoriatic lesions which are highly responsible for epidermal hyperproliferation and inflammation. Gallic acid (GA), a phenolic acid natural compound has potential inhibitory impact on pro-inflammatory transcription factors. However, the penetration across skin and availability is low when applied topically, making the treatment extremely challenging. Considering such factors, we developed GA loaded chitosan nanoparticles and modified with hyaluronic acid (HA) (HA@CS-GA NP) to assess the therapeutic potential against psoriasis. The formulations were characterized by DSC, zetasizer and TEM for assuring the development of nanosystems. GA loaded CS NP had a particle size of 207.2 ± 0.08 nm while after coating with HA, the size increased to 220.1 ± 0.18 nm. The entrapment efficiency was 93.24 ± 0.132% and drug loading of 73.17 ± 0.23%. The in vitro cell viability assessment study confirmed enhanced anti-proliferative effect of HA@CS-GA NP over plain GA which is due to high sensitivity towards HaCaT cell. The in vivo results on imiquimod induced psoriasis model indicated that CD44 receptor mediated targeted approach of HA@CS-GA NP gel had great potential in restricting the keratinocyte hyperproliferation and circumventing psoriasis. For the therapy of further skin-related conditions, HA modified nanoparticles should be investigated extensively employing genes, antibodies, chemotherapeutics, or natural substances.

摘要

银屑病是一种有害的自身免疫性疾病,严重危害患者的身心健康。研究发现,CD44 在银屑病皮损中过度表达,这是导致表皮过度增殖和炎症的主要原因。没食子酸(GA)是一种酚酸天然化合物,对促炎转录因子具有潜在的抑制作用。然而,当局部应用时,GA 的穿透皮肤和可用性较低,这使得治疗极具挑战性。考虑到这些因素,我们开发了负载 GA 的壳聚糖纳米粒子,并进行了透明质酸(HA)修饰(HA@CS-GA NP),以评估其治疗银屑病的潜力。通过 DSC、Zetasizer 和 TEM 对制剂进行了表征,以确保纳米系统的开发。载 GA 的 CS NP 的粒径为 207.2±0.08nm,而在涂覆 HA 后,粒径增加到 220.1±0.18nm。包封效率为 93.24±0.132%,载药量为 73.17±0.23%。体外细胞活力评估研究证实,HA@CS-GA NP 比普通 GA 具有更强的抗增殖作用,这是由于其对 HaCaT 细胞的高敏感性。在咪喹莫特诱导的银屑病模型中的体内结果表明,HA@CS-GA NP 凝胶的 CD44 受体介导的靶向方法在限制角质形成细胞过度增殖和避免银屑病方面具有很大的潜力。为了治疗进一步的皮肤相关疾病,应该广泛研究 HA 修饰的纳米粒子,以利用基因、抗体、化疗药物或天然物质。

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