Prevention of in vivo lung tumor growth by prolonged local delivery of hydroxycamptothecin using poly(ester-carbonate)-collagen composites

摘要

Local tumor recurrence has a major impact on long-term patient survival following the surgical treatment of most cancers, and this is especially true with lung cancer. Consequently, methods to deliver chemotherapeutics locally at a lung tumor resection margin would be beneficial since: 1) systemic treatment approaches are ineffective or highly toxic; 2) the incidence of local recurrence does not warrant universal treatment of all patients with a highly morbid systemic therapy; and 3) surgical resection of recurrent disease is not an option and alternative rescue therapies are generally unsuccessful. To begin to meet this clinical need, we have prepared poly(glycerol monostearate-co-ε-caprolactone) films as a controlled, prolonged, and low dose delivery matrix for the potent anticancer agent 10-hydroxycamptothecin (HCPT). These drug-loaded films were applied to a collagen-based scaffold clinically indicated for the mechanical buttressing of lung tissue following surgical resection, resulting in a flexible composite that can be secured to the tissue that releases HCPT over seven weeks and thereby prevents the local growth and establishment of Lewis lung carcinoma tumors in vivo (a freedom of local tumor growth of 86%). In comparison, all animals treated with a larger intravenous dose of HCPT or unloaded composites developed rapid local tumors.