Abstract

Natural products have been extensively used for treating a wide variety of disorders. In recent times, Brucine (BRU) as one of the natural medications extracted from seeds of nux vomica, was investigated for its anticancer activity. As far as we know, this is the first study on BRU anticancer activity against skin cancer. Thus, the rational of this work was implemented to develop, optimize and characterize the anticancer activity of BRU loaded ethosomal gel. Basically, thin film hydration method was used to formulate BRU ethosomal preparations, by means of Central composite design (CCD), which were operated to construct (32) factorial design. Two independent variables were designated (phospholipid percentage and ethanol percentage) with three responses (vesicular size, encapsulation efficiency and flux). Based on the desirability function, one formula was selected and incorporated into HPMC gel base to develop BRU loaded ethosomal gel. The fabricated gel was assessed for all physical characterization. In-vitro release investigation, ex-vivo permeation and MTT calorimetric assay were performed. BRU loaded ethosomal gel exhibited acceptable values for the characterization parameters which stand proper for topical application. In-vitro release investigation was efficiently prolonged for 6 h. The flux from BRU loaded ethosome was enhanced screening optimum SSTF value. Finally, in-vitro cytotoxicity study proved that BRU loaded ethosomal gel significantly improved the anticancer activity of the drug against A375 human melanoma cell lines. Substantially, the investigation proposed a strong motivation for further study of the lately developed BRU loaded ethosomal gel as a prospective therapeutic strategy for melanoma treatment.

Highlights

  • Nanotechnology is a discipline involves the design, development, characterization and application of nanoscale carrier systems in different aspects of nanomedicine [1]

  • Transdermal drug delivery systems have gained much attention owing to their high competence factors, such as more patient compliance, low frequency of dosing and avoiding many other problems usually related to the conventional oral dosage form [5]

  • The ethosomal gel is more applicable for skin treatment and was subjected to further evaluations to be compared with conventional BRU loaded gel

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Summary

Introduction

Nanotechnology is a discipline involves the design, development, characterization and application of nanoscale carrier systems in different aspects of nanomedicine [1]. Response surface methodology (RSM) is a tool that produces large amount of data from the least work It correlates with Central Composite Design (CCD) which is one of the most prevalent software that is based on specific mathematical, statistical equations and certain graphs for modeling the design [24,25]. In these contexts, BRU loaded into different ethosomal formulations was prepared, followed by characterization and optimization using CCD. It was examined for its in-vivo antitumor activity and compared to free drug, blank ethosome and conventional gels

Results
Characterization of the Developed BRU Loaded Ethosomal Gel
Morphological Evaluation
2.10. Ex-Vivo Investigation
Preparation of BRU Loaded Ethosome
Skin Permeation Study
Conclusions
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