SELF-ASSEMBLED PEG-SN38 NANOSYSTEMS
| Autor: | Berardi, Ginevra, Pulido, Daniel, Royo, Miriam |
|---|---|
| Rok vydání: | 2021 |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | The development of biocompatible and selective drug delivery systems still nowadays represents a crucial challenge for poorly soluble drugs used in cancer treatment [1]. For advanced colorectal cancer irinotecan (CPT-11), a soluble 7-ethyl-10-camptothecin (SN-38) derivative, is currently used in clinics. Since CPT-11 is only partially converted in its active metabolite, the development of other potential pro-drugs or drug delivery systems that release SN-38 in higher extension can generate more effective treatments with lower doses [2]. The covalent conjugation of SN-38 to a polymeric carrier, such as the biocompatible polyethylene glycol (PEG), generates a water-soluble conjugate with improved drug pharmacokinetic profile, protecting it from rapid degradation and stabilizing its bioactive closed-lactone form, allowing its systemic administration [3]. In this context, we have designed and synthesized diverse SN38-conjugates based on homo-bivalent and hetero-bivalent PEG-based platforms, where SN38 was conjugated through an ester bond at the C20 position. The use of a labile bond, sensitive to pH and esterases, can allow the stimuli-selective release of the intact drug. These systems have amphiphilic character due to the presence of a hydrophilic moiety of monodispersed PEG27 bound to a nitrilotriacetic acid core (NTA) [4] and a hydrophobic part containing SN38 and lipids (cholesterol or fatty acids). By adjusting the hydrophilic/hydrophobic ratio we obtain compounds able to self-assembly at ¿M concentration in aqueous media forming regular and nanostructures (10-15 nm or 40-60 nm) with different tridimensional shape, spherical or cylindrical depending on the chemical feature of the system. The preliminary results suggest that those compounds could be versatile candidates as SN38-delivery systems. References [1] Senapati S., Kumar A., Kumar S., et al., Sig. Transduct. Target Ther., 2018, 3. [2] Palakurthi S., Expert Opin Drug Deliv., 2015, 12, 1911-1921. [3] Zhao H., Rubio B., Sapra P., et al., Bioconj. Chem. 2008, 19, 849-859. [4] Pulido D., Albericio F., Royo M., Org. Letters. 2014, 16, 1318-1321. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|