Electrospray-mediated local chemotherapy of lung carcinoma in mice

Abstract

Invasive bronchogenic carcinoma may be fatal due to increasing airway obstruction with high mortality. Surgical removal of tumours remains the treatment of choice. Large numbers of patients with microscopic residual tumours (R1-resection) have recurrence and bad prognosis. Currently used radio and chemotherapy options are associated with complications. In the current study, we report the development of a novel therapeutic procedure to deliver approved chemotherapeutics directly in the tumour using novel non-invasive electrospray technique. Electrospray mediated local chemotherapy will act as an adjuvant offering palliative care by local administration of higher concentrations of chemotherapeutic drugs in the tumour while reducing side effects. C57BL mice were injected with 2x10'5 Lewis lung carcinoma LLC cells subcutaneously. After 15 days the animals were anesthetized and the tumours were electrosprayed with Methotrexate or Cisplatin; both with a dose of 100 µg/ml and 1 mg/ml concentration. Electrospray was performed at 2 time points. Tumour volume was measured every day for 8 days. The animals were sacrificed on 8^th day. 7 days after two electrospray with Methotrexate the tumour size was reduced and the growth was retarded to 22.46 mm³ ± 12.14 mm^{3 ,}similar effect was observed after Cisplatin electrospray (43.01 mm³± 16.92 mm³ vs 514.30 ± 104.50 mm³ in controls. We successfully demonstrated the feasibility of targeted drug delivery in the subcutaneous tumour by electrospray in mice model. A single port device has been developed, and successfully applied. Miniaturization of this concept will enable the application through a bronchoscope and offer a novel tool to target invasive bronchogenic carcinoma.