Role of chitosan coated invasomes in enhancement of transdermal delivery of tenoxicam for management of osteoarthritis: In vitro characterization, statistical optimization, ex vivo, and in vivo assessments

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2025-05-08 DOI:10.1016/j.ijpharm.2025.125700

Rania Moataz El-Dahmy , Mohamed A El-Nabarawi , Hassan Gamal Mostafa , Abeer Salama , Nermin M. Sheta

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引用次数: 0

Abstract

Tenoxicam (TNX) is a strong non-steroidal anti-inflammatory drug utilized to manage osteoarthritis. This study aimed to develop chitosan-coated invasomes (CCIs) for TNX transdermal delivery to enhance its solubility, transdermal permeability, and anti-osteoarthritic efficacy. TNX-invasomes were prepared using a thin-film hydration technique according to the 2².3¹ factorial design. The optimized CCI (OCCI) formula consisted of 100 mg L-alpha-phosphatidylcholine, 25 mg chitosan, and 100 mg limonene. The OCCI formula (F10) showed the minimum vesicle size (192.80 ± 4.60 nm), polydispersity index (0.252 ± 0.03), and maximum entrapment efficiency % (94.19 ± 3.77 %), zeta potential (46.10 ± 3.58 mV), % released after 24 h (86.83 ± 1.41 %), and transdermal flux (61.20 ± 2.35 μg/h.cm²). The OCCI formula showed higher stability compared with the conventional chitosan uncoated formula (F4). The OCCI formula was converted to OCCI gel that boosted TNX release by 2.17-fold compared to free TNX gel. The OCCI gel boosted TNX permeation by 1.61- and 5.27-fold compared to F4 gel and free TNX gel, respectively. In vivo skin irritation test verified the safety of the OCCI gel. Moreover, In vivo studies confirmed that OCCI gel achieved significant inhibition of cyclooxygenase-2 (COX2), prostaglandin E-2 (PGE2), and mitogen-activated protein kinase (MAPK) compared to TNX free gel and oral market tablet. Histopathological data confirmed the OCCI gel’s efficacy in cartilage regeneration. Therefore, OCCIs might be regarded as an effective approach for transdermal delivery of TNX to manage OA.

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壳聚糖包被侵入体在增强替诺昔康经皮给药治疗骨关节炎中的作用：体外表征、统计优化、体外和体内评估

替诺昔康（TNX）是一种用于治疗骨关节炎的强效非甾体抗炎药。本研究旨在开发用于TNX透皮给药的壳聚糖包被侵入体（CCIs），以提高TNX的溶解度、透皮渗透性和抗骨关节炎的功效。根据22.31因子设计，采用薄膜水化技术制备tnx -浸润体。优化后的CCI （OCCI）配方为：l - α -磷脂酰胆碱100 mg、壳聚糖25 mg、柠檬烯100 mg。OCCI配方（F10）显示最小囊泡大小（192.80±4.60 nm）、多分散指数（0.252±0.03）、最大包封效率%（94.19±3.77%）、zeta电位（46.10±3.58 mV）、24 h后释放率%（86.83±1.41%）、透皮通量（61.20±2.35 μg/h.cm2）。与常规壳聚糖无包覆配方（F4）相比，OCCI配方具有更高的稳定性。将OCCI配方转化为OCCI凝胶，与游离TNX凝胶相比，OCCI凝胶的TNX释放量增加了2.17倍。与F4凝胶和游离TNX凝胶相比，OCCI凝胶分别提高了TNX的1.61倍和5.27倍。体内皮肤刺激试验验证了OCCI凝胶的安全性。此外，体内研究证实，与TNX游离凝胶和口服市场片相比，OCCI凝胶对环氧化酶-2 （COX2）、前列腺素E-2 （PGE2）和丝裂原活化蛋白激酶（MAPK）具有显著的抑制作用。组织病理学数据证实了OCCI凝胶对软骨再生的疗效。因此，OCCIs可能被认为是TNX经皮给药治疗OA的有效途径。

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来源期刊

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.