Film/contact loading method improves the encapsulated amount of triazene anticancer compounds in polymeric micelles

The development of organic solvent-free methods for the encapsulation of hydrophobic molecules is necessary for advances in micelle-mediated drug delivery. In this study we investigated the film/contact approach in which the use of organic solvents is limited to the preparation of a dry film before encapsulation. Unloaded micelles of five structurally related block copolymers were placed in contact with thin homogeneous films of two hydrophobic triazene anticancer compounds (1-(4-amidophenyl)-3-(4-acetylphenyl)triazene (1) and corresponding triazenido complex with triphenylphosphanegold(I) fragment (2)). The micelle surface becomes saturated with the drug, which eventually penetrates as a front into the core. Because the drug interacts with both the shell and the core microenvironments of micelle during the process, the maximum loading capacities were very sensitive to block copolymer micelle composition, ranging from 2.2 to 20.4% (wt./wt. of polymer). We conclude that micelles with poly[2-(diisopropylamino)ethyl methacrylate] (PDPA) cores are the best option for the encapsulation of triazene compounds because i) they are prepared in absence of organic phase; ii) the drug concentration in the particles is high enough for a therapeutic effect and iii) the responsiveness properties of PDPA is appropriate for practical applications in pH-triggered drug release systems.

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► Loading of polymeric micelles by film/contact method is very sensitive to the particle composition.
► The chemical nature of both shell- and core-forming polymers determines the maximum drug loading capacity.
► Drug loading occurs by a two-step organic solvent-free process.
► The film/contact method is suitable for encapsulation of triazene anticancer compounds.