Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats

Acute lung injury (ALI) is a life-threatening illness which may progress to chronic pulmonary fibrosis (CPF). Resveratrol (RSV), a natural polyphenol, is known to exert several pharmacological effects on lung injury. However, its physicochemical properties and pharmacokinetic profile limit its clinical applications. In this study, RSV was loaded into lipid nanocapsules (LNCs) aiming to overcome these limitations. RSV-LNCs were prepared by phase inversion method and showed small uniform particle size (∼55 nm, PdI 0.04) with high entrapment efficiency >99%. The efficacy of RSV-LNCs in the prophylaxis against ALI and treatment of CPF was investigated in bleomycin-induced lung injury. For assessment of ALI, rats were administered a single oral dose of RSV (10 mg/kg) either free or as RSV-LNCs 4 h before bleomycin and euthanized 3 days later.

For CPF, treatments in the same dose were given daily from days 10–20 after bleomycin and rats were euthanized on day-21. Results showed enhanced beneficial role for RSV-LNCs, compared to RSV, in the prevention of ALI as demonstrated by preservation of pulmonary microscopic and ultrastructural architecture and improvement of pulmonary functions. Analysis of BALF revealed reduction in oxidative stress markers, IL-6 level, leukocytosis and neutrophilia. iNOS and c-caspase 3 immunohistochemical expression and CD68⁺ cells immunofluorescence were inhibited. However, RSV-LNCs failed to show any improvement in oxidative stress, chronic inflammation, apoptosis and collagen deposition in CPF. In conclusion, RSV-LNCs are promising nanoplatforms for mitigating ALI detrimental effects. Future research investigating higher doses and longer durations of treatment is recommended to evaluate RSV-LNCs anti-fibrotic potential in CPF.

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Materials

Resveratrol (RSV) was supplied by Ningbo Liwah Pharmaceutical Co., Ltd. (Zhejiang, China). Labrafac lipophile WL 1349 (caprylic-capric acid triglycerides, European Pharmacopeia, IVth, 2002) was a kind gift from Gattefossé S.A. (Saint-Priest, France). Kolliphor® HS 15 (a mixture of free polyethylene glycol 660 and polyethylene glycol 660 hydroxystearate, European Pharmacopeia, IVth, 2002) was provided by BASF (Ludwigshafen, Germany). Oleic acid (OA) was purchased from Sigma Aldrich (USA). Bleomycin (BLM) was purchased in the form of commercial Bleocel^® 15 IU Injection manufactured by celon Lab.

Neama M. Albanawany, Doaa M. Samy, Noha Zahran, Riham M. El-Moslemany, Shefaa Mf. Elsawy, and Maha W. Abou Nazel, Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats, DRUG DELIVERY2022, VOL. 29, NO. 1, 2592-2608, https://doi.org/10.1080/10717544.2022.2105445