Cytotoxicity of Thermally Manipulated Ethylene Oxide Polymers Used in Abuse Deterrent Formulations

Nova Southeastern University, Davie, Florida, USA

Objective. Evaluate human Gingiva derived stem cells (GMSCs) and Osteoblasts like cells (MG63) cells viability on heat-treated high and low molecular weight PEO films. Background. Features like low toxicity, lack of immunogenicity, antigenicity and excellent biocompatibility of PEO make it a preferred polymer in abuse deterrent formulations. However, PEO properties can change at higher temperature of abuse leading to oxidation and potential toxicity that is studied here. Methods. LMW (10% solution) and HMW (2% solution) PEO films were prepared by casting their solutions in glass petri-dish. The cells cultured on to a flat bottom 24 well plate with a density at 1X 105 were exposed to 60 mg/mL of sterilized PEO samples and allowed to incubate for 24 hours in 37°C. The cytotoxic effect of the PEO was assessed and the viability of the cells was determined by using the commercially available Live/Dead assay kit (Molecular probes Invitrogen detection technologies, Carlsbad, CA) Results. Cell viability in the presence of HMW 180°C and HMW 80°C films were compared with PEO control. The cell viability of both GMSCs and MG63 significantly reduced in HMW 180°C, while the cell viability in HMW 80°C was comparable to HMW control, Conclusion. Regardless of its molecular weight, PEO can become cytotoxic when heated at above 80°C. This is particularly important as abuse-deterrent tablets containing PEO are generally heated at high temperatures in order to abuse by injection and insufflation.