Pequi (Caryocar brasiliense Cambess)-Loaded Nanoemulsion, Orally Delivered, Modulates Inflammation in LPS-Induced Acute Lung Injury in Mice.

Diego De Sá Coutinho,Marco Aurelio Martins,Sílvia Stanisçuaski Guterres,Jader Pires,Patrícia Machado Rodrigues E Silva,Adriana Raffin Pohlmann,Hyago Gomes,Andressa Bernardi,Stela Regina Ferrarini

doi:10.3390/pharmaceutics12111075

Diego De Sá Coutinho, Marco Aurelio Martins + Show 7 more

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https://doi.org/10.3390/pharmaceutics12111075

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Abstract

Pequi is a Brazilian fruit used in folk medicine for pulmonary diseases treatment, but its oil presents bioavailability limitations. The use of nanocarriers can overcome this limitation. We developed nanoemulsions containing pequi oil (pequi-NE) and evaluated their effects in a lipopolysaccharide (LPS)-induced lung injury model. Free pequi oil or pequi-NE (20 mg/kg) was orally administered to A/J mice 16 and 4 h prior to intranasal LPS exposure, and the analyses were performed 24 h after LPS provocation. The physicochemical results revealed that pequi-NE comprised particles with mean diameter of 174–223 nm, low polydispersity index (0.11 ± 0.01), zeta potential of −7.13 ± 0.08 mV, and pH of 5.83 ± 0.12. In vivo evaluation showed that free pequi oil pretreatment reduced the influx of inflammatory cells into bronchoalveolar fluid (BALF), while pequi-NE completely abolished leukocyte accumulation. Moreover, pequi-NE, but not free pequi oil, reduced myeloperoxidase (MPO), TNF-α, IL-1β, IL-6, MCP-1, and KC levels. Similar anti-inflammatory effects were observed when LPS-exposed animals were pre-treated with the nanoemulsion containing pequi or oleic acid. These results suggest that the use of nanoemulsions as carriers enhances the anti-inflammatory properties of oleic acid-containing pequi oil. Moreover, pequi’s beneficial effect is likely due its high levels of oleic acid.

Highlights

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are inflammatory pulmonary disorders that result from various pathological insults, such as trauma, pneumonia, sepsis, endotoxemia, or multiple transfusions [1]
SPAN and polydispersity index (PDI) indicated the quality of the formulation, demonstrate the homogeneity, and amplitude of the droplet distribution
The results showed no significant difference in the average diameter of the drops of blank nanoemulsion (BNE), pequi-NE, oleic acid-NE in the period of 30 days, remaining with 187 ± 0.02, 230 ± 0.01, and 155 ± 0.00, respectively

Summary

Introduction

Acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), are inflammatory pulmonary disorders that result from various pathological insults, such as trauma, pneumonia, sepsis, endotoxemia, or multiple transfusions [1]. Despite the pathophysiology of ALI/ARDS being complex and not completely understood, it is known that neutrophils play a central role in these conditions by the release of granules and induction of oxidative injury, damaging the alveolar–capillary barrier [1,2]. Some studies have shown that pequi pulp contains several bioactive components with important anti-inflammatory, antioxidant, and healing properties, with oleic acid being the most predominant fatty acid [7,8]. Supplementation with pequi oil or its extract resulted in antioxidant and anti-DNA damage properties in mice exposed to urethane-induced oxidative lung damage [10]

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