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OKUMA, C. H. Development of lamellar gel phase emulsion with marigold oil (Calendula officinalis) and wound healing evaluation in cutaneous ulcers in rats. 2013. 90 p. Thesis (Doctoral Degree). Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, 2013. The aim of this research was to improve a lamellar gel phase emulsion containing Calendula officinalis oil and to investigate its potential as a modern wound dressing. First, we determined the region of the ternary phase diagram in which the emulsions were stable and we also evaluated the intrinsic stability of the system and the action of some parameters which may influence the formation of lamellar gel phase. In addition, we analyzed the samples’ behavior during the evaporation process. Moreover, an in vitro cytotoxicity assay of the calendula oil was performed in order to evaluate apoptosis and necrosis in fibroblast cell line L929. Then, an in vivo test was carried out by the wound healing rate (WHR), using a specific model of ulcer in rats (excisional contractile ulcer), in order to assess potential healing of the proposed emulsion (LGP) by comparing with the sham group. The ulcers were evaluated by image analysis at 0, 2, 7, 14 and 21 days after surgery. The emulsion 6 'showed greater stability in the preliminary and accelerated stability tests in relation to the previous studied formulation. Moreover, this formulation presented more compatible characteristics, because it showed smaller hysteresis area of η (thixotropy), therefore a lower degree of spreadability and, accordingly, the formulation may increase contact span with ulcer, which is a desirable characteristic. During evaporation of the emulsions, the anisotropic structures were maintained, but their type varied depending on the decreased amount of water in the system. The crude oil of Calendula officinalis showed no interference with the pathway of apoptosis and necrosis in the concentration of 1000 mg / mL in L929 fibroblasts. The proposed model has promoted better wound healing rate in the ulcers in the dorsal region of rats. It seemed to modulate the inflammatory phase of the healing process, because of the increased recruitment of inflammatory cells as well as collagenesis, once LGP emulsion decreased in the group, were factors essential that allowed total reepithelialization of skin ulcers in rats treated with LGP emulsion. In conclusion, this study produced an enhanced and useful LGP which can be used as a new approach to stimulate the healing process and treat wounds efficiently.

Desenvolvimento de emulsões com fase gel lamelar à base de óleo de calêndula (Calendula officinalis) e avaliação da atividade cicatricial em úlceras cutâneas de ratos