Within the implementation activities of the Drug-ReSQue project (PN-III-P1-1.1-PD-2021-0606, Contract No. PD 37 / 2022) during the period from April 1, 2022, to May 31, 2024, nine functional derivatives of squalene were obtained and structurally characterized. Among these, two derivatives represent the antitumor drugs Cytarabine and Methotrexate, which have been squalenized, and two derivatives represent the antimicrobial drugs Flucytosine and Curcumin, which have also been squalenized. Additionally, a polymeric derivative of squalene (SQ-PEG) was obtained through PEGylation. SQ-PEG was characterized structurally, morphologically, and behaviorally in aqueous solutions, while the squalenized drugs were structurally characterized. Furthermore, two antitumor nanotherapeutic formulations were developed, structurally and morphologically characterized, and tested in vitro on three cell lines (one normal and two tumor). These formulations were obtained by encapsulating Cytarabine and Methotrexate in micellar formations of PEGylated squalene. Moreover, three antifungal nanotherapeutic formulations were developed, characterized structurally and morphologically, and tested in vitro on 10 bacterial strains and a normal human cell line. These formulations were created by encapsulating Flucytosine, Curcumin, and a bifunctionalized derivative of Curcumin in micellar formations of PEGylated squalene. The results obtained during the Drug-ReSQue project implementation period were disseminated at four national and international conferences and were the subject of two scientific articles in high-impact ISI journals (Q1 and Q2).

The estimated impact of the results obtained

The studies carried out within the Drug-ReSQue project during the implementation period from April 1, 2022, to May 31, 2024, have generated a series of scientific results that are extremely important for both the scientific community and the general public. These results are particularly significant for improving the current administration methods of treatments for serious conditions, such as certain forms of cancer and fungal infections. The studies highlighted the importance of using micellar structures of PEGylated squalene (SQ-PEG) for the encapsulation, transport, and prolonged release of existing drugs in current treatment procedures. Among all the systems developed and studied within the Drug-ReSQue project, the nanotherapeutic system based on flucytosine encapsulated in SQ-PEG micelles was the most notable system due to its physicochemical properties and behavior in the in vitro studies. This system exhibited prolonged release over 48 hours, significantly reduced toxicity on the normal HGF cell line, and increased antimicrobial efficiency against two strains of Candida glabrata and Candida parapsilosis compared to the unencapsulated drug, with the most encouraging results observed for C. parapsilosis. In conclusion, the encouraging results that were obtained recommend the use of these systems for further in vivo studies.