Orthoesters hydrolyze at varying rates in an acidic environment depending on their size and functionalization. By synthesizing molecules with a hydrophobic oleoyl group and hydrophilic polyethylene glycol chain on opposite ends of a cyclic orthoester, water-soluble micelles can be used to house a hydrophobic drug, such as the chemotherapeutic doxorubicin, and deliver it within the body. By altering the size and functionalization of the ring incorporating the orthoester, the rate of hydrolysis and thus drug release from the micelle can be controlled. Three orthoester molecules with differing sizes and functionalization were synthesized and characterized. The critical micelle concentrations of all three different orthoester micelles were below 60 μg/mL, and their hydrodynamic diameters were determined to be between 60 and 100 nm. Micelles were loaded with doxorubicin using a dialysis technique, and their drug loading efficiencies were measured to be between 3 and 10% at a drug/orthoester molecule feed ratio of 30% (w/w). Feed ratios lower than 30% (w/w) resulted in lower drug loading efficiencies. The hydrolysis of the orthoesters was monitored using dynamic light scattering (DLS) and <sup>1</sup>H NMR spectroscopy, and both showed strong evidence of acid-catalyzed hydrolysis over 48 hours at extracellular tumor pH.

Tunable acid-labile orthoester micelles for use in targeted drug delivery

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.