This study aimed at improving the systemic bioavailability of propranolol-HCl by the design of transdermal drug delivery system based on chitosan nanoparticles dispersed into gels. Chitosan nanoparticles were prepared by ionic gelation technique using tripolyphosphate (TPP) as a cross-linking agent. Characterization of the nanoparticles was focused on particle size, zeta potential, surface texture and morphology, and drug encapsulation efficiency. The prepared freeze dried chitosan nanoparticles were dispersed into gels made of poloxamer and carbopol and the rheological behaviour and the adhesiveness of the gels were investigated. The results showed that smallest propranolol loaded chitosan nanoparticles were achieved with 0.2% chitosan and 0.05% TPP. Nanoparticles were stable in suspension with a zeta potential (ZP) above ±30mV to prevent aggregation of the colloid. Zeta potential was found to increase with increasing chitosan concentration due to its cationic nature. At least 70% of entrapment efficiency and drug loading were achieved for all prepared nanoparticles. When chitosan nanoparticles dispersed into gel consisting of poloxamer and carbopol, the resultant formulation exhibited thixotropic behaviour with a prolonged drug release properties as shown by the permeation studies through pig ear skin. Our study demonstrated that the designed nanoparticles-gel transdermal delivery system has a potential to improve the systemic bioavailability and the therapeutic efficacy of propranolol-HCl.