In Vivo Evaluation of the Antitumor Peptide CIGB- 552: Antitumor Activity, Pharmacokinetics and Safety of the Subcutaneously Administered Peptide

Background/Objectives: The CIGB-552 peptide is a novel therapeutic alternative for the treatment of cancer. In this study, we aimed to determine the optimal formulation and route of administration for CIGB-552. Other objectives were to characterize the peptide's pharmacokinetic profile in rats and conduct toxicity studies at different dosage regimens. Methods: The antitumor activity of CIGB-552 was evaluated by different routes of administration (intraperitoneal, subcutaneous) and also with different peptide formulations (Tartrate/mannitol, Tartrate/trehalose) using a TC-1 tumor model in C57BL/6 mice. The pharmacokinetic profile of the peptide was also characterized after subcutaneous administration in Sprague-Dawley rats using PK Solver software. In addition, the safety of the peptide was evaluated following single-dose and repeated-dose administration schedules in healthy BALB/c mice. Results: In the tumor model, subcutaneous administration of CIGB-552 and its formulation with tartrate/trehalose resulted in a significant reduction in tumor volume compared to untreated groups. CIGB-552 presented a typical extravascular administration profile with rapid absorption, along with a rapid tissue distribution phase and rapid blood clearance. The peptide's half-life was 2.5 h, and peak plasma concentration (Cmax) was reached within approximately 15 min. Furthermore, CIGB-552 administration in the evaluated regimens was safe, with toxicity and lethal outcomes only at the 60 mg/kg dose. Conclusions: The peptide’s safety profile in repeated dosing, combined with evidence of no systemic accumulation, supports the development of new regimens involving higher and more frequent doses to enhance antitumor efficacy in clinical studies.