We explored a series of cyclodextrin (CyD) polymers composed either of a single CyD type or a mixture of two CyD types to encapsulate simultaneously different compounds with potential therapeutic interest for multimodal prostate cancer treatment. New mixed CyD polymers were prepared in alkaline water starting from the naturally occurring monomers and a low-cost crosslinking agent. Batches of 200 g of polymer were easily obtained. By means of optical spectroscopy we proved the co-encapsulation of 3 compounds in the polymers: the drugs cabazitaxel (CBX) and bicalutamide (BIC), and the photosensitizer chlorin e6 (Ce6). p beta CyD and mixed p alpha beta CyD polymers performed best for single drug solubilization. In the co-encapsulation of BIC and CBX by p beta CyD and p alpha beta CyD, p beta CyD stands out in drug solubilization ability. Avoiding the use of organic solvents, it was possible to dissolve up to 0.1 mM CBX with 10 mg ml(-1) p beta CyD polymer and, with 100 mg ml(-1), even 1.7 mM BIC, a 100-fold improvement compared to water. Spectroscopic studies afforded the binding constants of CBX and BIC with p beta CyD forming complexes of 1 : 2 stoichiometry (drug : CyD) and CBX displayed significantly higher affinity. Also DFT calculations suggested that the drugs are more stable when complexed by two CyD units. Ce6 could be encapsulated simultaneously with the other two drugs in p beta CyD and, most importantly, is able to produce singlet oxygen efficiently. Thanks to a single inexpensive CyD-based polymer we were able to produce a three-in-one platform for future implementation of combined chemotherapy and photodynamic therapy. These achievements are most relevant as nanomedicines are continuously proposed but their potential for translation to the pharma industry is compromised by their limited potential for industrial upscale.
Three-in-one: exploration of co-encapsulation of cabazitaxel, bicalutamide and chlorin e6 in new mixed cyclodextrin-crosslinked polymers
Agnes;Marco;Manet;Ilse
2023
Abstract
We explored a series of cyclodextrin (CyD) polymers composed either of a single CyD type or a mixture of two CyD types to encapsulate simultaneously different compounds with potential therapeutic interest for multimodal prostate cancer treatment. New mixed CyD polymers were prepared in alkaline water starting from the naturally occurring monomers and a low-cost crosslinking agent. Batches of 200 g of polymer were easily obtained. By means of optical spectroscopy we proved the co-encapsulation of 3 compounds in the polymers: the drugs cabazitaxel (CBX) and bicalutamide (BIC), and the photosensitizer chlorin e6 (Ce6). p beta CyD and mixed p alpha beta CyD polymers performed best for single drug solubilization. In the co-encapsulation of BIC and CBX by p beta CyD and p alpha beta CyD, p beta CyD stands out in drug solubilization ability. Avoiding the use of organic solvents, it was possible to dissolve up to 0.1 mM CBX with 10 mg ml(-1) p beta CyD polymer and, with 100 mg ml(-1), even 1.7 mM BIC, a 100-fold improvement compared to water. Spectroscopic studies afforded the binding constants of CBX and BIC with p beta CyD forming complexes of 1 : 2 stoichiometry (drug : CyD) and CBX displayed significantly higher affinity. Also DFT calculations suggested that the drugs are more stable when complexed by two CyD units. Ce6 could be encapsulated simultaneously with the other two drugs in p beta CyD and, most importantly, is able to produce singlet oxygen efficiently. Thanks to a single inexpensive CyD-based polymer we were able to produce a three-in-one platform for future implementation of combined chemotherapy and photodynamic therapy. These achievements are most relevant as nanomedicines are continuously proposed but their potential for translation to the pharma industry is compromised by their limited potential for industrial upscale.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.