Avaliação in vivo de formulações tópicas contendo asiaticosídeo no tratamento da morfeia

Author(s)

Laura Moretti Aiello

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Farmacêuticas
• Defense date: 2023-07-11

Examining board members

Gislaine Ricci Leonardi; Patrícia Maria Berardo Gonçalves Maia Campos; Paulo Eduardo Neves Ferreira Velho

• Advisor: Gislaine Ricci Leonardi; Andréa Fernandes Eloy da Costa França

Abstract

Introduction: Localized Scleroderma or Morphea is an inflammatory, autoimmune, and chronic disease. Clinical observations indicate that asiaticoside, extracted from Centella asiatica, is a potential active ingredient in improving morphea lesions by regulating collagen synthesis. Biophysical and skin imaging methods can assist in the clinical diagnosis of the disease in a non-invasive and objective manner. The study aimed to understand the behavior of morphea lesions using biophysical methods and skin imaging. Additionally, through these techniques, it sought to assess the impact of topically applying the active compound asiaticoside on these lesions. Methods: Six different emulsions containing 1% asiaticoside and their corresponding vehicles were developed. After preliminary stability analysis, one of the emulsions was selected for clinical testing. The clinical study involved lesion characterization through dermatological, clinical and instrumental evaluation. Skin biomechanical behavior was extensively studied using Cutometer® R parameters. An efficacy study of asiaticoside application was also conducted on twenty patients with morphea. Formulations with or without asiaticoside were applied twice daily for 4 months. The efficacy of these formulations was evaluated clinically by a dermatologist, patient self-assessment, and by biophysical and skin imaging methods before and after 60, 90, and 120 days. Results and Discussion: The emulsion composed of the self-emulsifying agent C12 - C20 Acid PEG-8 ester was selected for in vivo evaluation in morphea patients. In the characterization clinical study, significant surface changes were observed, including decreased hydration, increased transepidermal water loss, increased skin stiffness (R0), reduced biological elasticity (R7), and higher skin temperature, indicating a biophysical impairment of the skin in the sclerosis process. Dermatoscopy revealed areas of fibrosis, alterations in vascularization, and skin pigmentation. Ultrasound findings with an 11MHz transducer showed significant thickness and echogenicity alterations in the subcutaneous tissue. In the efficacy study, the degree of sclerosis was significantly reduced with asiaticoside use according to dermatological clinical evaluation. These findings are consistent with the significant reduction in subcutaneous tissue echogenicity. In biometric and dermatoscopic findings, the percentage variations in all parameters evaluated were statistically equivalent after using emulsions with or without asiaticoside. Participants reported an overall improvement in the evaluated parameters in lesions treated with emulsions with and without asiaticoside. Conclusions: All biophysical and imaging methods included in the study proved to be important complementary tools in the characterization and evaluation of scleroderma lesions. Although biometric findings indicate a similar effect of the vehicle and asiaticoside formulation on the superficial layers of the lesion through biometric analysis, dermatological clinical evaluation and ultrasound findings demonstrate the potential action of asiaticoside in reducing skin sclerosis. Future studies may consider a larger sample size for segmented lesion analysis according to subtype, disease stage, and anatomical regions, aiming to reduce variability in measurements (AU)

• FAPESP's process: 20/12443-8 - In vivo evaluation of topical formulations containing asiaticoside for treatment of morphea
• Grantee: Laura Moretti Aiello
• Support Opportunities: Scholarships in Brazil - Master