Irinotecan (IRN) is a semisynthetic derivative of
camptothecin that acts as a
topoisomerase I inhibitor. IRN is used worldwide for the treatment of several types of
cancer, including
colorectal cancer, however its use can lead to serious adverse effects, as
diarrhea and myelosuppression.
Liposomes are widely used as drug delivery systems that can improve chemotherapeutic activity and decrease side effects.
Liposomes can also be pH-sensitive to release its content preferentially in acidic environments, like
tumors, and be surface-functionalized for targeting purposes. Herein, we developed a
folate-coated pH-sensitive
liposome as a drug delivery system for IRN to reach improved
tumor therapy without potential adverse events.
Liposomes were prepared containing IRN and characterized for particle size, polydispersity index, zeta potential, concentration, encapsulation, cellular uptake, and release profile. Antitumor activity was investigated in a murine model of
colorectal cancer, and its toxicity was evaluated by hematological/biochemical tests and histological analysis of main organs. The results showed vesicles smaller than 200 nm with little dispersion, a surface charge close to neutral, and high encapsulation rate of over 90%. The system demonstrated prolonged and sustained release in pH-dependent manner with high intracellular drug delivery capacity. Importantly, the
folate-coated pH-sensitive formulation had significantly better antitumor activity than the pH-dependent system only or the free drug.
Tumor tissue of IRN-containing groups presented large areas of
necrosis. Furthermore, no evidence of systemic toxicity was found for the groups investigated. Thus, our developed nanodrug IRN delivery system can potentially be an alternative to conventional
colorectal cancer treatment.