Scheme 1.

Schematic illustration of pH‐responsive myristic acid‐conjugated quetiapine nanosuspension (QMN) for enhanced in vitro and in vivo performance and long‐acting delivery. Quetiapine myristate (QM), a lipophilic prodrug synthesized from quetiapine (QTP) and myristic acid, can be converted to QTP by plasma esterase. In an acidic buffer, QM self‐assembles to form positively charged 200‐nm sized QMN with good injectability, stability, and drug loading efficiency. Following intramuscular injection in beagle dogs, QMN undergoes physiological pH‐responsive structural rearrangement, forming nanoaggregates at the injection site for long‐acting performance with minimized initial burst release compared with conventional poly(lactide‐co‐glycolide) (PLGA) nanosuspensions loaded with QTP or QM.