Temperature-responsive delivery of chemotherapy drugs from ethyl cellulose nanofibers incorporating a biocompatible fatty acid phase change material

Localized stimuli-responsive delivery systems for chemotherapy drugs have the potential to revolutionize therapeutic outcomes by offering greater selectivity, thereby reducing systemic side effects and bolstering patient benefits. In this work, Ethyl cellulose (EC) nanofibers were prepared using electrospinning, encapsulating both doxorubicin HCl (DOX) and Rhodamine B (RhB) as representative hydrophilic chemotherapy and model drugs, respectively, and lauric acid (LA) as a biocompatible phase change material (PCM). LA’s melting point is slightly above normal body temperature, enabling temperature-responsive release. The temperature response of drug release was examined by measuring release rates at ~25 °C, 37 °C, and 40 °C. In vitro release profiles demonstrated a distinct temperature-dependent release pattern: a noteworthy 27% increase in release for DOX and a 10% for RhB at pH 7.4 at 40 °C compared to 37 °C. Additionally, the release mechanism of DOX showcased pronounced pH sensitivity, evidenced by an increase of 41% in release at the more acidic pH 4 when the temperature was increased from 37 °C to 40 °C, combined with a noticeable reduction in the initial burst release. Further evaluations using HEK-293 cells indicated the prolonged efficacy of the DOX-embedded nanofibers, underscoring their therapeutic potential. Advanced analytical techniques, such as DSC, XRD, and FTIR, revealed an amorphous state of the active pharmaceutical ingredient (API) and a harmonious integration of the PCM within the system. Our EC drug delivery system (DDS) demonstrated potential for targeted, stimuli-responsive DOX release, which could revolutionize its traditional administration, particularly in post-surgical scenarios to prevent tumor recurrence.