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)viaa dialysis method; the critical micelle concentrations (CMCs) were recorded to be 0.03 mg mL−1and 0.00193 mg mL−1for EC-PEG1 and EC-PEG2, respectively. The physicochemical properties of the respective nano-micelles were evaluatedviavarious characterization techniques. The morphologies of the nano-micelles were analyzedviatransmission electron microscopy (TEM), and the average size of the nano-micelles was recorded to be ∼80 nm.In vitro, 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 studyviafluorescence 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 furthervia in vivostudies to understand its potential as a controlled DDS to treat cancer.