Incorporation and release behavior of amitriptylene in core–shell–corona type triblock copolymer micelles

A cationic antidepressant drug, amitriptylene (AMT), was successfully incorporated into core–shell–corona micelles of poly[styrene-b-sodium 2-(acrylamido)-2-methyl-1-propanesulfonate-b-ethylene oxide] (PS-b-PAMPS-b-PEO). Zeta-potential measurements revealed that both electrostatic and hydrophobic interactions contributed to the binding of the drug to the polymer. The AMT/PS-b-PAMPS-b-PEO nanocomplexes were characterized by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The hydrodynamic diameter of the AMT loaded nanocomplexes decreased from 80 to 40 nm depending on the amount of the drug loaded on the polymer. This is attributed to the cancellation of the negative charge of the PAMPS group by the cationic drug. The AMT/PS-b-PAMPS-b-PEO nanocomplexes were stable in aqueous solution exhibiting no aggregation or no precipitation for several months. Release of the AMT from the nanocomplexes was investigated in vitro in salt-free and 0.1 M NaCl solutions. The drug was released faster in the 0.1 M NaCl solution than in the salt-free solution. This is due to the shielding effect of the salt on the electrostatic interaction. However, in both cases, the drug release mainly occurs by the Fickian diffusion mechanism.

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► PS-b-PAMPS-b-PEO forms core–shell–corona type micelles in aqueous solution.
► A cationic drug preferentially binds on shell domain of micelles.
► Frozen PS core stabilizes the nanocomplexes even in extremely diluted condition.
► PEO corona participates in stabilization of nanocomplexes from aggregation.