Banca de DEFESA: MAGNALDO INÁCIO TAVARES MEDEIROS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : MAGNALDO INÁCIO TAVARES MEDEIROS
DATE: 22/02/2022
TIME: 08:30
LOCAL: Online (remota)
TITLE:

Colloidal SNEDDS systems of Croton cajucara BENTH applied on in vivo experimental models for analgesic, inflammation and wound healing

 

KEY WORDS:

Croton cajucara Benth; non-volatile oil; trans-dehydrocrotonin; SNEDDS-type loading systems; analgesic and anti-inflammation activities; wound healing therapeutic process.

PAGES: 159
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Systemic chronic inflammation (SCI) and chronic wounds have been widely treated, but the adverse effects attributed to medications limit prolonged treatments. In this present study Croton cajucara Benth medicinal species was applied as an alternative therapy, by using in vivo models, aiming at to analyze its analgesia, inflammation and wound healing. In that, were used the non-volatil oil (so called fixed oil, FO) and the diterpine trans-dehydrocrotonin obtained from this herbal stem bark. After chromatographic studies, FO and t-DCTN were loaded into a colloidal self-nanoemulsion drug delivery system (SNEDDS-type) aiming at the carrier biocompatibility with FO and t-DCTN, as well as reductions of therapeutic doses and toxic risks, maintenance of the constant level of the drug in the blood (by controlled release of the SNEDDS systems), and prolonged efficacy of the systems therapeutic effects. Based on the polar colloidal O/A (oil in water) systems the formulation SNEDDS was prepared by using Tween® 80 and a vegetable oil of food use (in low concentrations), dispersed in a neutral aqueous medium (with high concentration). The target SNEDDS system was characterized by physicochemical analyses and showed droplet diameter with reduced scale (11 nm), and showed to be biocompatible with FO and t-DCTN. Since it is a system free of cosurfactant, reinforces the proposal of pharmacological application in prolonged periods, due to the reduction in the number of the carrier ingredients and also by applying minimized concentrations of the assayed bioactives from C. cajucara. The SNEDDS-derivatives were called SNEDDS-OFCC (containing 15 mg of fixed oil, rich in sesquiterpenes) and SNEDDS-DCTN (containing 5 mg of t-DCTN). These nanobioproducts were administered orally in experimental pain models through abdominal contortions and formalin tests. Treatment with SNEDDS-OFCC formulation showed 40.2% inhibition in central pain (neuropathic) and 42.8% in inhibition of peripheral inflammatory pain. Meanwhile, SNEDDS-DCTN in reducing abdominal contortions was effective in 76.7%, and in the formalin test inhibited 47.9% (neuropathic pain) and 52.6% (peripheral pain). In the models of inflammation (paw edema and peritonitis) dexamethasone (0.5 mg/kg, s.c.) was used as positive control. The inhibitor rates of leukocyte migration (by carrageenan-induced inflammation) showed significant reductions for the peritoneal cavity, with inhibitions 29.4% for SNEDDS-OFCC and 38% for SNEDDS-DCTN, in relation to the negative control group (vehicle). In the paw edema inhibition, 69.5% was observed for SNEDDS-OFCC and 89.7% for SNEDDS-DCTN. Based on these data, the SNEDDS-DCTN system was used in the experimental healing model, administered topically in Wistar rat lesions (7, 14 and 21 days). For each experimental group, the retraction index (morphometry) of the lesion and the tissue behavior (histopathological and immunohistochemical analysis) were observed. The rate of lesion retraction on the 14th day was quantitative (98.3%), compared to 43.7% for the 7th day, and also to the negative control group. The histopathological analyses sowed reduction in inflammation, with significant gains in cell proliferation and tissue maturation, compared to the control group. Since, SNEDDS-OF and SNEDDS-DCTN presented associated antinociceptive and anti-inflammatory action, as well as healing (SNEDDS-DCTN), so, they may meet a specific demand from patients who are on prolonged treatments (SCI-type) to combat pain and inflammation caused by skin lesions or chronic inflammations.

BANKING MEMBERS:
Presidente - 373.201.654-49 - MARIA APARECIDA MEDEIROS MACIEL - UnP
Externo ao Programa - 2941160 - JOSE HERIBERTO OLIVEIRA DO NASCIMENTO
Externo à Instituição - RICARDO LUIZ CAVALCANTI DE ALBUQUERQUE JUNIOR - UNIT
Externa à Instituição - TEREZINHA GONÇALVES DA SILVA - UFPE
Externo à Instituição - VALDIR FLORENCIO DA VEIGA JUNIOR - IME