Compositions and methods are provided for preparing nanosized biologically active agents, including agents formulated for target specific drug delivery. The nanosized agents are prepared with supercritical carbon dioxide as an antisolvent, providing nanoparticles whose size, shape, and surroundings are well-controlled. The nanoparticles are made of small molecules, e.g. drugs, anti-oxidants, luciferin, polypeptides, e.g. oligopeptides; polynucleotides, e.g. siRNA, antisense oligonucleotides, etc. In some embodiments, the nanoparticles comprise a polymer coating, which can provide for controlled delivery, targeting, controlled release, and the like. In other embodiments, the nanoparticles comprise a target specific tag for targeting the nanoparticles to a site of interest, e.g. tissue, cell, etc.