Incorporation of camptothecin into reduction-degradable supramolecular micelles for enhancing its stability

• CPT supramolecular micelles of mPEG-Ad@BAC-CDen/CPT were obtained by incorporation of CPT into mPEG-Ad@ BAC-CDen via dialysis method.
• Owing to the reduction degradability of disulfide linker in main chain of BAC-CDen, the CPT sustainably release from micelles together with the gradual cleavage of polymer.
• MPEG-Ad@BAC-CDen supramolecular micelles effectively protected the active lactone ring of CPT from hydrolysis under physiological condition.
• Compared with free CPT, the CPT-loaded supramolecular micelles showed essential decreased cytotoxicity against L929 cell line.

In this research, a reduction-degradable supramolecular micelle delivery system of camptothecin (CPT) was developed to enhance the stability of CPT in aqueous media. Firstly, Michael addition polymerization occurred between N, N’-bis(acryloyl) cystamine (BAC) and mono(6-(2-aminoethyl)amino-6-deoxy)-β-cyclodextrin (CDen) to produce the reduction-degradable polymer of BAC-CDen. And adamantyl-modified polyethylene glycol monomethyl ether (mPEG-Ad) was further encapsulated into it to gain supramolecular micelles of mPEG-Ad@BAC-CDen. Then mPEG-Ad@BAC-CDen/CPT supramolecular micelles could be easily obtained by incorporation of CPT into mPEG-Ad@BAC-CDen via dialysis method. The particle size of supramolecular micelles increased from 106 nm (bare micelles) to 142 nm (CPT loaded micelles), suggesting their passive targeting potential to tumor tissue. Owing to the reduction degradability of disulfide linker in main chain of BAC-CDen, the CPT could be sustainably released from the above micelles with the gradual cleavage of polymer in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition. It was noted that the stability of CPT in aqueous media was remarkably improved in the mPEG-Ad@BAC-CDen supramolecular micelles, which effectively protected the active lactone ring of CPT from hydrolysis under physiological condition. Besides, compared with free CPT, the CPT-loaded supramolecular micelles showed much lower cytotoxicity against L929 cell line. All these results suggested the potential utilization of the mPEG-Ad@BAC-CDen supramolecular micelles as the carriers of hydrophobic drugs with better stability and lower cytotoxicity. And the resulted anti-tumor CPT supramolecular micelles can be delivered to tumor cells with a high selectivity.

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