Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity

Author(s): Swaminathan S, Pastero L, Serpe L, Trotta F, Vavia P, et al.

Abstract

Camptothecin (CAM), a plant alkaloid and a potent antitumor agent, has a limited therapeutic utility because of its poor aqueous solubility, lactone ring instability and serious side effects. Cyclodextrin-based nanosponges (NS) are a novel class of cross-linked derivatives of cyclodextrins. They have been used to increase the solubility of poorly soluble actives, to protect the labile groups and control the release. This study aimed at formulating complexes of CAM with three types of beta-cyclodextrin NS obtained with different cross-linking ratio (viz. 1:2, 1:4 and 1:8 on molar basis with the cross-linker) to protect the lactone ring from hydrolysis and to prolong the release kinetics of CAM. Crystalline (F(1:2), F(1:4) and F(1:8)) and paracrystalline NS formulations were prepared. XRPD, DSC and FTIR studies confirmed the interactions of CAM with NS. XRPD showed that the crystallinity of CAM decreased after loading. CAM was loaded as much as 21%, 37% and 13% w/w in F(1:2), F(1:4) and F(1:8), respectively while the paracrystalline NS formulations gave a loading of about 10% w/w or lower. The particle sizes of the loaded NS formulations were between 450 and 600nm with low polydispersity indices. The zeta potentials were sufficiently high (-20 to -25mV) to obtain a stable colloidal nanosuspension. The in vitro studies indicated a slow and prolonged CAM release over a period of 24h. The NS formulations protected the lactone ring of CAM after their incubation in physiological conditions at 37 degrees C for 24h with a 80% w/w of intact lactone ring when compared to only around 20% w/w of plain CAM. The cytotoxicity studies on HT-29 cells showed that the CAM formulations were more cytotoxic than plain CAM after 24h of incubation.

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