In this work, pH-sensitive amphiphilic macromolecules are designed to possess good biocompatibility and drug loading while employing an acid-sensitive linkage to trigger drug release at tumor tissues. Specifically, two pH-sensitive amphiphilic macromolecules were synthesized with a hydrazone linkage between the hydrophobic and hydrophilic segments. The chemical structure, molecular weight, critical micelle concentration, micelle size, and pH-triggered cleavage of the amphiphilic macromolecules were characterized via matrix-assisted laser desorption/ionization time-of-flight, nuclear magnetic resonance, and dynamic light scattering techniques. Drug loading and release as well as cytotoxicity studies were performed using doxorubicin. Hydrodynamic diameters of the micelles formed with pH-sensitive amphiphilic macromolecules were within an optimal range for cellular uptake. The critical micelle concentration values were 10–8–10–6 M, indicating micellar stability upon dilution. The degradation products of the amphiphilic macromolecules after acidic incubation were identified using mass spectrometry, nuclear magnetic resonance, and dynamic light scattering methods. A pH-dependent release profile of the doxorubicin-encapsulated amphiphilic macromolecules was observed. Cytotoxicity studies against two cancer cell lines, MDA-MB-231 human breast cancer cells and A549 lung cancer cells, showed that doxorubicin encapsulated in pH-sensitive amphiphilic macromolecules decreased cell viability more efficiently than free doxorubicin, possibly due to the toxicity of the amphiphilic macromolecule degradation products. Resulting from enhanced release at acidic pH due to hydrolysis of the hydrazone linkage, pH-sensitive amphiphilic macromolecules also had improved efficacy toward cancer cells compared to other carriers (e.g. Pluronics®). These findings indicate that pH-sensitive amphiphilic macromolecules can potentially be applied as anticancer drug delivery vehicles to achieve controlled release and improved therapeutic effects.
Kinetic Study of Peroxidase-Catalyzed Oxidation of 2-Hydroxyanthracene and 9-Phenanthrol in Presence of Biosurfactant Escin
