The MSCA-IF Polar Star project funded by the EC aimed at the development of a novel administration route for multiple therapeutic agents using a nanotechnology based on CD-polymers enabling the synergic combination in a unique carrier of classical chemotherapy with androgen deprivation and photodynamic therapies (PDT), aiming to develop a novel multimodal prostate cancer treatment.
In this frame, a series of CD-polymers were evaluated as plausible carriers: already reported CD-polymers composed of a single CD type (α, β or γ) were compared to newly synthesized mixed CyD polymers (α-β, β-γ and α-γ) by means of optical spectroscopy and computational analysis.
Co-encapsulation and solubilization in water of 3 compounds, 2 drugs (cabazitaxel, CBX, and bicalutamide, BIC) and 1 photosensitizer (Chlorin e6, Ce6) were achieved in the presence of pβCD and mixed pαβCD polymers which allowed to reach an increase in solubility up to 100-fold compared to water. Spectroscopic studies confirmed the formation of mainly 1 : 2 (drug : CD) complexes with binding constants log K1:2 in the range 6.8-10.2, while Ce6 displayed a log K1:2 ≈ 4. DFT calculations confirmed the enhanced stabilization of the complexes when 2 CD units are present in the same binding event. Moreover, the 3 components could be simultaneously encapsulated without affecting the ability of Ce6 to produce singlet oxygen efficiently.
The use of a single inexpensive CD-based polymer was thus proved to be a suitable three-in-one platform for future implementation of combined therapies, exploiting structural details which could drastically affect pharmacokinetic and -dynamic profiles, the already existing scale-up production of these materials at affordable costs and the use of protocols assuring reproducibility of multiple batches.
Three-in-one: exploration of co-encapsulation of cabazitaxel, bicalutamide and chlorin e6 in new mixed cyclodextrin-crosslinked polymers – E. Pancani, D. Veclani, M. Agnes, A. Mazza, A. Venturini, M. Malanga and I. Manet, RSC Adv. 2023, 13, 10923. DOI: https://doi.org/10.1039/D3RA01782F