Objective: The objective of this study is to develop a new solubility enhancement strategy of antipsychotic drug - perphenazine (PPZ) - in the form of its amorphous nanoparticle complex (or nanoplex) with polyelectrolyte dextran sulfate (DXT). Significance: Poor bioavailability of PPZ necessitated the development of fast-dissolving PPZ formulations regardless of delivery routes. Existing fast-dissolving formulations, however, exhibited low PPZ payload. The high-payload PPZ-DXT nanoplex represents an attractive fast-dissolving formulation, as dissolution rate is known to be proportional to payload. Methods: The nanoplex was prepared by electrostatically driven complexation between PPZ and DXT in a simple process that involved only ambient mixing of PPZ and DXT solutions. We investigated the effects of key variables in drug-polyelectrolyte complexation (i.e. pH and charge ratio R-DXT/PPZ) on the physical characteristics and preparation efficiency of the nanoplex produced. Subsequently, we characterized the colloidal and amorphous state stabilities, dissolution enhancement, and supersaturation generation of the nanoplex prepared at the optimal condition. Results: The physical characteristics of nanoplex were governed by R-DXT/PPZ, while the preparation efficiency was governed by the preparation pH. Nanoplex having size of approximate to 80nm, zeta potential of approximate to(-) 60mV, and payload of approximate to 70% (w/w) were prepared at nearly 90% PPZ utilization rate and approximate to 60% yield. The nanoplex exhibited superior dissolution than native PPZ in simulated intestinal juice, resulting in high and prolonged apparent solubility with good storage stabilities. Conclusions: The simple yet efficient preparation, excellent physical characteristics, fast dissolution, and high apparent solubility exhibited by the PPZ-DXT nanoplex established its potential as a new bioavailability enhancement strategy of PPZ.