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Healing activity of hydrogel containing nanoemulsified β-caryophyllene.
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2020-03-20 , DOI: 10.1016/j.ejps.2020.105318 Jonathan Parisotto-Peterle 1 , Juliana Bidone 2 , Letícia Grolli Lucca 1 , Gabriela de Moraes Soares Araújo 2 , Mariana Corrêa Falkembach 2 , Magno da Silva Marques 3 , Ana Paula Horn 3 , Maíra Kerpel Dos Santos 1 , Valdir Florêncio da Veiga 4 , Renata Pereira Limberger 1 , Helder Ferreira Teixeira 1 , Cristiana Lima Dora 2 , Letícia Scherer Koester 1
European Journal of Pharmaceutical Sciences ( IF 4.3 ) Pub Date : 2020-03-20 , DOI: 10.1016/j.ejps.2020.105318 Jonathan Parisotto-Peterle 1 , Juliana Bidone 2 , Letícia Grolli Lucca 1 , Gabriela de Moraes Soares Araújo 2 , Mariana Corrêa Falkembach 2 , Magno da Silva Marques 3 , Ana Paula Horn 3 , Maíra Kerpel Dos Santos 1 , Valdir Florêncio da Veiga 4 , Renata Pereira Limberger 1 , Helder Ferreira Teixeira 1 , Cristiana Lima Dora 2 , Letícia Scherer Koester 1
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β-caryophyllene is a sesquiterpene present in the oil of many plant species, such as Copaifera sp., which has been shown to possesses potent anti-inflammatory action; however, its healing activity remains under study. The objectives of the present study were to produce a nanoemulsion containing β-caryophyllene followed by a hydrogel containing nanoemulsified β-caryophyllene, to evaluate the permeation profile in vitro, and to assess the in vivo healing activity, which is so far unexplored in the literature for pure β-caryophyllene and in pharmaceutical formulation. The nanoemulsion was obtained through high-pressure homogenization and the hydrogel by direct dispersion with hydroxyethylcellulose. Both formulations were characterized according to droplet size, polydispersity index, volume-weighted mean diameters, particle distribution, droplets diameters tracking, zeta potential, viscosity and bioadhesion behavior. β-caryophyllene content was determined by gas chromatography coupled with mass spectrometry (GC/MS). Both formulations presented a nanometric droplet size, negative zeta potential, high β-caryophyllene content, and were stable for 60 days. In agreement with the viscosity results, the hydrogel containing the β-caryophyllene nanoemulsion showed superior bioadhesiveness than the nanoemulsion. The skin permeation study in Franz cells demonstrated that isolated β-caryophyllene was unable to cross the stratum corneum and that its nanoemulsification promoted its permeation. On the other hand, in the simulated deeply wounded skin (dermis), no significant differences were observed between the formulations and isolated β-caryophyllene with respect to the amount of marker retention in the dermis, suggesting saturation of this skin layer. For the study of healing activity, the dorsal wound model was performed with an evaluation of the lesion size, anti-inflammatory markers, and antioxidant activity. The initial closure of the wound was achieved sooner in the group treated with the hydrogel containing the β-caryophyllene nanoemulsion, indicating its anti-inflammatory effect. The histological analysis indicated that on day 12 day of the lesion, the hydrogel presented similar results to those of the positive control group (Dersani® oil), proving effectiveness in cutaneous tissue repair.
中文翻译：
含有纳米乳化的β-石竹烯的水凝胶的修复活性。
β-石竹烯是一种倍半萜烯，存在于许多植物油中，例如Copaifera sp。，已被证明具有有效的抗炎作用。然而，其愈合活性仍在研究中。本研究的目的是生产一种含有β-石竹烯的纳米乳剂，然后生产一种含有纳米乳化的β-石竹烯的水凝胶，以评估其体外渗透特性，并评估其体内的愈合活性，这在文献中尚待探讨。用于纯β-石竹烯和药物制剂。通过高压均化获得纳米乳液，并通过与羟乙基纤维素直接分散获得水凝胶。两种配方均根据液滴尺寸，多分散性指数，体积加权平均直径，颗粒分布，液滴直径跟踪，ζ电势，粘度和生物粘附行为。β-石竹烯含量通过气相色谱-质谱联用（GC / MS）测定。两种制剂均表现出纳米液滴尺寸，负ζ电位，高β-叶绿素含量，并且稳定60天。与粘度结果一致，包含β-石竹烯纳米乳液的水凝胶显示出比纳米乳液优异的生物粘合性。在Franz细胞中进行的皮肤渗透研究表明，分离的β-石竹烯无法穿过角质层，并且其纳米乳化促进了其渗透。另一方面，在模拟的严重受伤的皮肤（真皮）中，在真皮中标记物保留量方面，在制剂和分离的β-石竹烯之间没有观察到显着差异，表明该皮肤层已饱和。为了研究愈合活性，进行了背伤口模型，并评估了病变大小，抗炎标记和抗氧化活性。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。评估伤口大小，抗炎标记和抗氧化活性，进行背侧伤口模型。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。评估伤口大小，抗炎标记和抗氧化活性，进行背侧伤口模型。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。
更新日期：2020-03-21
中文翻译：
含有纳米乳化的β-石竹烯的水凝胶的修复活性。
β-石竹烯是一种倍半萜烯，存在于许多植物油中，例如Copaifera sp。，已被证明具有有效的抗炎作用。然而，其愈合活性仍在研究中。本研究的目的是生产一种含有β-石竹烯的纳米乳剂，然后生产一种含有纳米乳化的β-石竹烯的水凝胶，以评估其体外渗透特性，并评估其体内的愈合活性，这在文献中尚待探讨。用于纯β-石竹烯和药物制剂。通过高压均化获得纳米乳液，并通过与羟乙基纤维素直接分散获得水凝胶。两种配方均根据液滴尺寸，多分散性指数，体积加权平均直径，颗粒分布，液滴直径跟踪，ζ电势，粘度和生物粘附行为。β-石竹烯含量通过气相色谱-质谱联用（GC / MS）测定。两种制剂均表现出纳米液滴尺寸，负ζ电位，高β-叶绿素含量，并且稳定60天。与粘度结果一致，包含β-石竹烯纳米乳液的水凝胶显示出比纳米乳液优异的生物粘合性。在Franz细胞中进行的皮肤渗透研究表明，分离的β-石竹烯无法穿过角质层，并且其纳米乳化促进了其渗透。另一方面，在模拟的严重受伤的皮肤（真皮）中，在真皮中标记物保留量方面，在制剂和分离的β-石竹烯之间没有观察到显着差异，表明该皮肤层已饱和。为了研究愈合活性，进行了背伤口模型，并评估了病变大小，抗炎标记和抗氧化活性。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。评估伤口大小，抗炎标记和抗氧化活性，进行背侧伤口模型。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。评估伤口大小，抗炎标记和抗氧化活性，进行背侧伤口模型。在用含有β-石竹烯纳米乳的水凝胶治疗的组中，伤口的早期闭合较早实现，表明其抗炎作用。组织学分析表明，在病变的第12天，水凝胶的结果与阳性对照组（Dersani®油）相似，证明在皮肤组织修复中有效。
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