Modeling the Effect of Composition on Formation of Aerosolized Nanoemulsion System Encapsulating Docetaxel and Curcumin Using D-Optimal Mixture Experimental Design.

Azren Aida Asmawi,Mohd Basyaruddin Abdul Rahman,Norazlinaliza Salim,Emilia Abdulmalek

doi:10.3390/ijms21124357

Abstract

The synergistic anticancer effect of docetaxel (DTX) and curcumin (CCM) has emerged as an attractive therapeutic candidate for lung cancer treatment. However, the lack of optimal bioavailability because of high toxicity, low stability, and poor solubility has limited their clinical success. Given this, an aerosolized nanoemulsion system for pulmonary delivery is recommended to mitigate these drawbacks. In this study, DTX- and CCM-loaded nanoemulsions were optimized using the D-optimal mixture experimental design (MED). The effect of nanoemulsion compositions towards two response variables, namely, particle size and aerosol size, was studied. The optimized formulations for both DTX- and CCM-loaded nanoemulsions were determined, and their physicochemical and aerodynamic properties were evaluated as well. The MED models achieved the optimum formulation for DTX- and CCM-loaded nanoemulsions containing a 6.0 wt% mixture of palm kernel oil ester (PKOE) and safflower seed oils (1:1), 2.5 wt% of lecithin, 2.0 wt% mixture of Tween 85 and Span 85 (9:1), and 2.5 wt% of glycerol in the aqueous phase. The actual values of the optimized formulations were in line with the predicted values obtained from the MED, and they exhibited desirable attributes of physicochemical and aerodynamic properties for inhalation therapy. Thus, the optimized formulations have potential use as a drug delivery system for a pulmonary application.

Highlights

Cancer is one of the leading causes of death globally, and lung cancer tops the mortality rate with the lowest survival rate among all the cancers [1]
The linear polynomial model matched with the experimental data of volume median diameter (VMD) for both DTX- and CCM-loaded nanoemulsion formulations
The present study highlights the D-optimal mixture experimental design (MED) as being a potent tool to study optimization, which involved in the formulation of DTX and CCM-loaded nanoemulsions to attain small particle size and VMD

Summary

Introduction

Cancer is one of the leading causes of death globally, and lung cancer tops the mortality rate with the lowest survival rate among all the cancers [1]. Among the most potent of chemotherapeutic drugs used for lung cancer treatment are taxanes, which comprise docetaxel (DTX). This type of treatment is always riddled with dose-limiting side effects and drug resistance issues [2,3]. The synergistic anticancer effect exhibited by DTX and CCM may potentiate the treatment of lung cancer and make them attractive therapeutic drug candidates. Due to their hydrophobic nature, both DTX and CCM are usually associated with slow drug absorption and low stability leading to inadequate maximum bioavailability for the therapeutic response [7,8]

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Conclusion