The aim of this study was to develop innovative nanosystems with isopropyl myristate as the oil core of self-assembly nanovesicles constituted of chitosan and lecithin using a 2(3) factorial design. The factors analyzed were chitosan (X1, levels 4 and 8 mg/ml), oil (X2, levels 10 and 20 mg/ml) and lecithin (X3, levels 4 and 8 mg/ml). The responses evaluated were diameter, zeta potential, pH, viscosity, and backscattering analysis. The bioavailability was evaluated after oral administration of clozapine free and nanoencapsulated in rats. The diameter ranged from 0.348 to 1.5 µm for F2 (X1, 4; X2, 10; X3, 8 mg/ml) and F7 (X1, 8; X2, 20; X3, 4 mg/ml), respectively. Laser diffractometry analysis revealed only one diameter population for all batches. Zeta potential was positive, being influenced by X1 and X2/X3 association. Viscosity values were dependent on the X1 and X2 concentrations used. A structure proposed for the nanosystem consists of chitosan forming the hydrophilic shell layer that protects the core comprised of lecithin and the hydrophobic groups of oil. The AUC0-∞ was almost 3 times higher with the clozapine nanoencapsuted in relation to free drug. It was developed a new nanosystem which is able of improving the absorption of drugs.