There are many considerations for the effective delivery of pharmaceuticals within the body, such as solubility, stability during circulation, targeting to specific cells, cellular internalization, intracellular trafficking and proper function once inside. These properties are determined both by the chemical structure of the drug molecule and the delivery agent. Drug delivery agents can be used to improve upon these properties by packaging the drug, providing reactive sites for targeting ligands and/or interacting with cell surfaces. Often, these delivery agents are micelles that can carry hydrophobic drugs and release their contents in a controlled way. Three new micelle delivery agents were synthesized from polyethylene glycol (PEG) and oleic acid linked through orthoesters. Orthoesters hydrolyze at varying rates in different pH environments and with different structural modifications; therefore, ring size and functional groups were varied. Characterization included determining critical micelle concentrations (CMCs), orthoester hydrolysis rates, and drug loading efficiency using NMR, DLS, spectrofluorimetry, and UV-visible spectroscopy. CMCs were determined to range from 38.9 μg/mL to 56.2 μg/mL, with larger ring size and phenyl subsitution increasing the CMC. One orthoester compound was seen to hydrolyze in buffers less than pH 5.5, which is ideal for drug release inside endosomes. These orthoester micelles will be further studied for their potential as a delivery agent for the chemotherapeutic doxorubicin to enhance its bioavailability and pharmacokinetics.

Acid-labile oleoyl-PEG orthoester micelles for controlled drug delivery

253rd National Meeting (2017)

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