Optimization of Production Parameters for Andrographolide-Loaded Nanoemulsion Preparation by Microfluidization and Evaluations of Its Bioactivities in Skin Cancer Cells and UVB Radiation-Exposed Skin.

Rathapon Asasutjarit,Asira Fuongfuchat,Adryan Fristiohady,Kriyapa Lairungruang,Nawarat Sooksai,Shiow-Fern Ng

doi:10.3390/pharmaceutics13081290

Abstract

Andrographolide (AG) is an active compound isolated from Andrographis paniculata (Family Acanthaceae). Although it possesses beneficial bioactivities to the skin, there is insufficient information of its applications for treatment of skin disorders due to low water solubility leading to complications in product development. To overcome the problem, an AG-loaded nanoemulsion (AG-NE) was formulated and prepared using a microfluidization technique. This study aimed to investigate the effect of pressure and the number of homogenization cycles (factors) on droplet size, polydispersity index and zeta potential of AG-NE (responses) and to determine the effect of AG-NE on skin cancer cells and UVB irradiation-induced skin disorders in rats. Relationships between factors versus responses obtained from the face-centered central composite design were described by quadratic models. The optimum value of parameters for the production of optimized AG-NE (Op-AG-NE) were 20,000 psi of pressure and 5 homogenization cycles. Op-AG-NE showed promising cytotoxicity effects on the human malignant melanoma- (A375 cells) and non-melanoma cells (A-431 cells) via apoptosis induction with a high selectivity index and also inhibited intracellular tyrosinase activity in the A375 cells. Op-AG-NE could reduce melanin index and healed UVB irradiation exposed skin. Op-AG-NE thus had potential for treatment of skin cancers and skin disorders from exposure to UVB radiation.

Highlights

Andrographolide (AG) is one of diterpenoids isolated from stems and leaves of Andrographis paniculata (Family Acanthaceae), a medicinal plant used as an ingredient in remedies for fever, cold, sore throat and diarrhea in China, Japan, India, Southeast Asia and Europe [1,2]
The objectives of this study were (1) to investigate the effect of pressure and number of homogenization cycles on droplet size, PDI and zeta potential of AG-loaded nanoemulsion (AG-NE) prepared by microfluidization technique; (2) to determine cytotoxicity of AG-NEs to the normal skin cells and skin cancer cells; and (3) to determine the effect of AG-NE on UVB irradiationinduced skin pigmentation and skin damage
10,000 rpm for 30 min, which was an accelerated stability test and performed immediately after they were prepared. Their droplet size, PDI, and zeta potential of AG-NEs are shown in Table 2 as observed values of the responses. They implied that all AG-NEs possessed droplet size in a nanometer range with moderately broad droplet size distribution and low negative values of zeta potential

Summary

Introduction

Andrographolide (AG) is one of diterpenoids isolated from stems and leaves of Andrographis paniculata (Family Acanthaceae), a medicinal plant used as an ingredient in remedies for fever, cold, sore throat and diarrhea in China, Japan, India, Southeast Asia and Europe [1,2]. The pharmacological activities of AG have been extensively investigated. This terpene-based compound exhibited strong bioactivities for treatment. Pharmaceutics 2021, 13, 1290 of various diseases, for example, diseases related to inflammation [2], viral and bacterial infection [1], central nervous system disorders [3], including cancers, e.g., leukemia, breast cancer and non-melanoma [1,4,5]. Its water-soluble derivative, AG sodium bisulfite, could prevent skin photoaging in mice [6]. It had promising activities for suppressing melanin synthesis in mice exposed to ultraviolet (UV) radiation [7]. AG has attracted attention for skin disorder management, skin pigmentation, skin cancer and skin damage from

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