PEGylated ethyl cellulose micelles as a nanocarrier for drug delivery

Abstract

Natural polymers provide a better alternative to synthetic polymers in the domain of drug delivery systems (DDSs) because of their renewability, biocompatibility, and low immunogenicity; therefore, they are being studied for the development of bulk/nanoformulations. Likewise, current methods for engineering natural polymers into micelles are in their infancy, and in-depth studies are required using natural polymers as controlled DDSs. Accordingly, in our present study, a new micellar DDS was synthesized using ethyl cellulose (EC) grafted with polyethylene glycol (PEG); it was characterized, its properties, cell toxicity, and hemocompatibility were evaluated, and its drug release kinetics were demonstrated using doxorubicin (DOX) as a model drug. Briefly, EC was grafted with PEG to form the amphiphilic copolymers EC-PEG1 and EC-PEG2 with varying PEG concentrations, and nano-micelles were prepared with and without the drug (DOX) <i>via</i> a dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL^-1 and 0.00193 mg mL^-1 for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluated <i>via</i> various characterization techniques. The morphologies of the nano-micelles were analyzed <i>via</i> transmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm. <i>In vitro</i>, drug release studies were done for 48 h, where 100% DOX release was recorded at pH 5.5 and 52% DOX release was recorded at pH 7.4 from the micelles. In addition, cytotoxicity studies suggested that DOX-loaded micelles were potent in killing MDA-MB-231 and MCF-7 cancer cells, and the blank micelles were non-toxic toward cancerous and normal cells. A cellular uptake study <i>via</i> fluorescence microscopy indicated the internalization of DOX-loaded micelles by cancer cells, delivering the DOX into the cellular compartments. Based on these studies, we concluded that the developed material should be studied further <i>via in vivo</i> studies to understand its potential as a controlled DDS to treat cancer.