BACKGROUND Camptothecin (CPT) is an anticancer drug, and is not employed in the clinic because of its high hydrophobicity and low active form stability. CPT may also have potential for use in cold preservation. OBJECTIVE To overcome these drawbacks, CPT solubility variations in the presence of cyclodextrins (CDs) and polyethylene glycol (PEG) were evaluated by Higuchi solubility experiments. METHODS CPT was encapsulated in different cyclodextrins and polyethylene glycol using a co-evaporation method. The CPT interactions with CDs and PEG 6000 were investigated by Fourier-transformed infrared spectroscopy (FT-IR), and X-ray powder diffraction (XRPD). Then, CPT complexes were evaluated for in-vitro drug release. To evaluate the potential anticancer efficacy of the CPT complexes system, in-vitro cytotoxicity studies on human red blood cells were carried out using UV assay. The impact of the CPT complex systems on sperm motility protection during cold preservation at 4 degree C was studied using CASA. RESULTS The dissolution profile of these preparations shows the improvement of the dissolution of the CPT following a fickien diffusion. The CPT solubility and stability improvement were the cause of the cytotoxicity on the red blood cells test. However, CPT alone, encapsulated, dispersed, and chemically modified protected spermatozoids during cold preservation. CONCLUSIONS We confirm the interest in CPT encapsulated and dispersed in anticancer treatments. We also found that CPT encapsulated or dispersed could protect sperm against oxidative damage and improve the membrane integrity of human sperm. Consequently, CPT encapsulated our dispersed could eventually be beneficial for infertility therapy. Doi: 10.54680/fr23210110712.