Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells.

Iulia Pinzaru,Alina Tanase,Lavinia Vlaia,Iasmina Marcovici,Codruta Soica,Cristina Dehelean,Virgil Enatescu,Claudia Watz,Dorina Coricovac,Flavia Bociort

doi:10.3390/antiox10010085

Abstract

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders.

Highlights

In recent years it became clearer the fundamental role of oxidative stress in the development of different chronic maladies such as neurodegenerative diseases, cardiovascular pathologies, diabetes, aging, and cancer, leading to an increased interest in compounds with antioxidant properties [1]
Skin is considered the largest barrier of the body and a target for oxidative stress induced by different external stressors (UV radiation, food additives, drugs, cosmetics, air pollutants, etc.) or endogenous factors, effects that are directly correlated with various cutaneous disorders
Regarding the average size and distribution of these types of biodegradaand rutin-loading led to a slight change in the zeta potential to a more negative value ble polymers, an increase in the size of proniosomes can be observed on a rutin basis com(Figure 2)

Summary

Introduction

In recent years it became clearer the fundamental role of oxidative stress in the development of different chronic maladies such as neurodegenerative diseases, cardiovascular pathologies, diabetes, aging, and cancer, leading to an increased interest in compounds with antioxidant properties [1]. Even though BCC and SCC have a higher incidence as compared to melanoma, melanoma is responsible for most of the skin cancer-related deaths due to its metastatic behavior [7,8,9]. Another rare type of skin cancer known for its aggressiveness and for its high rate of lethality is Merkel cell carcinoma [10]

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