Supramolecular filaments containing a fixed 41% paclitaxel loading

Abstract

We report here the self-assembly of a rationally designed paclitaxel drug amphiphile into well-defined supramolecular filaments that possess a fixed 41% paclitaxel loading. These filaments can exert effective cytotoxicity against a number of cell lines comparable to that of free paclitaxel.

Linker-determined drug release mechanism of free camptothecin from self-assembling drug amphiphiles

“…Taking into account the supramolecular nature of DA 1 , 8a the data obtained suggests the mechanism shown in Fig. 2f as a possible explanation for the observed disulphide formation and subsequent stability.…”

“…2 Such a prodrug strategy has been used to create peptide–drug conjugates, 3 polymer–drug conjugates, 4 dendrimer–drug conjugates, 5 nanoparticle–drug conjugates, 6 and most recently drug-based molecular hydrogelators 7 and self-assembling drug amphiphiles. 8 Indeed, the linkage of a hydrophilic segment to a hydrophobic anticancer drug to create self-assembling amphiphiles offers the means to create self-delivering drugs that possess a high and fixed drug content, allowing for the minimum use of excipients. These self-assembling prodrugs combine the processability of small molecules with the controlled pharmacokinetics potential offered by larger structures such as polymer–drug conjugates.…”

“…8 Our initial design 8a connected the hydrophobic anticancer drug camptothecin 15 to a hydrophilic β-sheet forming Tau-derived peptide 16 via a reducible disulfanyl butyrate (buSS) linker. The single CPT-containing buSS-linked drug amphiphile displayed a much reduced activity when compared with free CPT, an observation that may be due to the release of the active drug.…”

“…To probe the release of CPT from the buSS-linked drug amphiphile, CPT-buSS-Tau ( 1 ), 8a we performed a more mechanistic study of its glutathione (GSH)-induced degradation using HPLC and LC-MS analyses at relatively low (5 µM) and high (50 µM) concentrations. This allows us to explore the degradation behaviour close to and much higher than the critical assembly concentration, which was previously found to be sub-micromolar.…”

“…This allows us to explore the degradation behaviour close to and much higher than the critical assembly concentration, which was previously found to be sub-micromolar. 8a Following the initial reduction of the buSS linker, a dynamic mixture of products is expected to form through a series of disulphide exchange and hydrolysis reactions (Fig. 2a).…”