Size-Controlled Preparation of Docetaxel- and Curcumin-Loaded Nanoemulsions for Potential Pulmonary Delivery

Abstract

Lung cancer is one of the deadliest pulmonary diseases in the world. Although docetaxel (DTX) has exhibited superior efficacy in lung cancer treatment, it has demonstrated numerous adverse effects and poor bioavailability. The natural product extract, curcumin (CCM), has reportedly reduced toxicity and synergistically improved DTX bioavailability. Nonetheless, the hydrophobic nature of DTX and CCM limits their clinical use. Nanoemulsion pulmonary delivery of DTX and CCM has demonstrated potential as a drug carrier to alleviate these drawbacks. The controlled preparation of inhalable DTX- and CCM-loaded nanoemulsions within the 100 to 200 nm range was explored in this study. A response surface methodology (RSM) based on a central composite design (CCD) was utilized to fabricate the desired size of the nanoemulsion under optimized conditions. Different process parameters were employed to control the size of the nanoemulsions procured through a high-energy emulsification technique. The size of the resultant nanoemulsions decreased with increasing energy input. The actual response according to the targeted sizes for DTX- and CCM-loaded nanoemulsion models exhibited excellent agreement with the predicted value at below 5% residual standard error under optimized conditions. The nanoemulsion of 100 nm particle size demonstrated better membrane permeability than their larger counterparts. Moreover, the formulations documented favorable physicochemical and aerodynamic pulmonary delivery properties and reduced toxicity in human lung fibroblast (MRC-5) cells. Hence, this tunable size of nanoemulsions could be a suitable alternative drug delivery for pulmonary diseases with increased local lung concentration.