Many chemical agents have low solubility which makes their dispersion, admixing and delivery difficult. Ball milling is often used to disperse such materials; however, dry powders are not always convenient for further applications [1]. For liquid hydrophobic materials, such as oil, there is a well established procedure of emulsification which allows for the stable dispersion of microdrops in water [2][3]. In this paper, we discuss a method for converting solid materials into stable aqueous nanocolloids with a particle size of ca 200 nm through simultaneous powerful ultrasonication and layer-by-layer (LbL) polyelectrolyte coating. It is a development of LbL microencapsulation introduced by G. Sukhorukov, E. Donath, F. Caruso, H. Möhwald, Most of these works are exploiting the formation of nano/engineered polyelectrolyte shells on pre-formed microtemplates with much larger diameters of 1 to 5 μm [11][12][13][14][15][16][17][18].There is a number of publications on micronizing drug or dye particles and building LbL shells on them, typically containing 4 to 10 polyelectrolyte bilayers and allowing a slow particle dissolution time from minutes up to 3-4 hours through adjustable capsule wall thickness (wall thickness of 20-50 nm) [9][10]19]. LbL shell coated dye particles were used as paint additives [11]. Soluble drugs, such as furosemide, nifedipine, naproxen , biotin, vitamin K3 and insulin were mechanically crushed into a dry powder and used for LbL shell assembly at a pH where they have low solubility in order to preserve the drug microcores from dissolution during the preparation [12][13][14][15]. Typical particle sizes of such a formulation were 2-10 micrometers [14]. In another approach, LbL microcapsules were assembled on sacrificed micro-cores (2-5 μm CaCO 3 , MnCO 3 , or silica). Then these cores were dissolved and the empty shells were loaded with proteins or drugs through pH controlled capsule wall opening [13][14][15]. Induced drug release is also possible with light responsive capsule opening [16]. Contrary to the first case of solid drug cores, these microshells contained a relatively low amount of loaded materials (1-5 vol %). Laser confocal microscopy allowed for the detailed studying of the structure of such microcapsules, proving the location of the loaded drugs and demonstrating their penetration into cells [17]. However, this successful development did not allow for the capsules to be sized on the nanometer scale.We are describing a method to prepare stable aqueous nanocolloids of low soluble materials (solubility less than 0.005 mg/mL) having particle diameters in the range of 150-250 nm. This approach is based on the powerful sonication of powders of low soluble materials in the presence of a polyelectrolyte which is adsorbing charging particles and preventing smaller and smaller pieces from re-aggregation. At the first preparation step, one has a colloidal dispersion of materials coated with a layer of polycations which provides a surface ξ-potential of ca +35 mV. Deposition of the second anio...