Study the property of double-ended fluoroalkyl poly(ethylene glycol) hydrogel as a depot for hydrophobic drug delivery using electron paramagnetic resonance technique and cell proliferation assay

Hydrogel formed by fluoroalkyl double-ended polyethylene glycol (R_f-PEG) micelles was studied to assess its properties to encapsulate a hydrophobic electron spin labeled drug, Chlorambucil–Tempol adduct (CT), and to control and sustain the drug release. The drug loaded hydrogel samples were characterized with variable-temperature dependent EPR experiment, and EPR theoretical lineshape analysis. It was found that CT molecules reside in the hydrophobic R_f-cores/IPDU shells of the R_f-PEG micelles and the maximum molecular-level loading capacity was estimated to be 18.8 mg per gram of the R_f-PEG. It has been known that R_f-PEG hydrogel with certain molecular masses for the fluoroalkyl group and the PEG chain shows properties of sol/gel phase coexistence and surface erosion, which represent the favorable condition for a pharmaceutical depot to control the kinetics of drug release. To evaluate the R_f-PEG's biocompatibility and kinetics of the drug release, a cell proliferation assay was carried out on human oropharyngeal carcinoma (KB) cells. The results show that R_f-PEG is biocompatible and able to release CT to the cell media with a constant equilibrium concentration independent of the amount of CT loaded hydrogel.