Solid lipid nanoparticles (SLNs) are sub-micron colloidal carriers having a size range of 50–1000 nm. These are prepared with physiological lipid and dispersed in water or aqueous surfactant solution. Bosutinib (BST) is a BCS Class II drug having very low solubility and high permeability. Low aqueous solubility and poor dissolution of BST leads to poor bioavailability, Thus, limited aqueous solubility is the bottleneck for the therapeutic outcome of BST. Animal data suggests that the absolute bioavailability of BST is about 14 to 34% due to an extensive first-pass effect. To overcome hepatic first-pass metabolism and to enhance oral bioavailability, lipid–based drug delivery systems like solid lipid nanoparticles can be used. These systems enhance the lymphatic transport of the lipophilic drugs and therefore increase the bioavailability. Bosutinib can be conveniently loaded into solid lipid nanoparticles to improve the oral bioavailability by exploiting the intestinal lymphatic transport. The objective of this present investigation is enhancing the solubility and bioavailability of the drug Bosutinib by incorporating with different lipids such as dynasan 114, 116 and 118 by exploiting the intestinal lymphatic transport. The Bosutinib loaded solid lipid nanoparticles (BST-SLN) were prepared by hot homogenization followed by ultra-sonication method. The prepared SLN’s were characterized for particle size, PDI, Zeta potential, EE, Total drug content and in vitro release study and its kinetic models.