Avaliação do efeito cicatrizante do óleo de copaíba veiculado em sistemas SNEDDS e processos terapêuticos em modelo experimental in vivo de lesões cutâneas

Abstract

Chronic wound management comprises an important aspect of medical practice and requires specific treatment for effective therapeutic treatment. Historical records show that copaiba oil is used preferentially to promote wound healing and treat inflammatory and infectious diseases. However, its low solubility in water limits its pharmacological use. In this sense, in the present research, selfnanoemulsion drug delivery systems (SNEDDS) developed by using lowconcentration (0.5%) of copaiba oil (CO) were prepared in the presence of Tween® 80 and aqueous (neutral or saline) medium. The encapsulation of this bioactive oil in a SNEDDS-type system allows its slow and prolonged release with topical application in an experimental procedure for the healing of diabetic and non-diabetic wounds. Physical-chemical analyzes were performed to characterize the in natura CO and also encapsulated in SNEDDS formulations. The CO-nanoformulations were prepared without the use of co-surfactant, which justifies its foremost importance in pharmacological applications, due to the reduction of carrier ingredients that may cause adverse reactions. Specifically, the SNEDDS contain copaiba oil and sunflower oil (1:1) as oil phase, variable percentages of surfactant (Tween class) and water on neutral or saline pH. The SNEDDS-CO systems were evaluated in therapeutic healing procedures, in which the in vivo assays for wound healing (uninfected and infected) were performed on Wistar rats (Rattus novergicus albinus). The animals were divided into groups of 5 animals (n = 5), submitted to surgery to remove cutaneous flap in the dorsal region and received daily topical treatment with SNEDDS-CO systems during the postoperative period. Histopathological and immunohistochemical analysis were performed after 7 and 14 days of treatment for both groups. Histomorphometric analysis revealed a lower number of neutrophils and lymphocytes in the treated groups (7 days), as well as increased collagenesis, proliferation of fibroblasts and increased epithelial thickening, which by comparison were more evident in the treated groups (14 days). In the control groups, the delay in tissue repair was related to the presence of keratinocytes as a function of the increased immunoreactivity for IL-1β. The highest number of cells immunocornized with FGF-2 was associated with the improvement of collagenase and the tissue repair process. In addition, an in vivo comparative approach of therapeutic procedures was performed in an experimental model of cutaneous lesions, in which the effect of low intensity laser therapy (LILT) on angiogenesis and immunoexpression of matrix metalloproteinase-2 was evaluated in the absence and/or presence of SNEDDS-CO systems.