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Abstract. The use of biodegradable polymers simplifies the development of therapeutic devices with regards to transient implants and three-dimensional platform suitable for tissue engineering. Further advances have also occurred in the controlled released mechanism of bioactive compounds encapsulated in biodegradable polymers. This application requires the understanding of the physicochemical properties of the polymeric materials and their inherent impact on the delivery of encapsulated bioactive. Hence, the objective of this study was to evaluate the effect of surfactant and sonication time on the bio-accessibility of lycopene encapsulated polymeric nanoparticles. The emulsion evaporation method was used to encapsulate lycopene in poly-lactic co-glycolic acid (PLGA) with surfactant concentration, sonication time and polymer concentration as independent variables. Physicochemical and morphological characteristics were measured with a zetasizer and SEM, while the encapsulation efficiency and controlled release kinetics with spectrophotometric, and the dialysis method was used to estimate bioaccessibility. The results have shown sonication time to have significantly (p < 0.05) influenced the encapsulation efficiency. Hence, the sonication time of 4 min yield an encapsulation efficiency of 78% and increased to 97% with increase sonication time (6 min). Increased sonication time had a decreasing effect on the hydrodynamic diameter and stability of the encapsulated nanoparticles. The slow release of lycopene was observed during the first 12 days, followed by a burst release of about 44% on the 13th day in-vitro. The study will have significant impact on the manufacturing of functional food with encapsulated ingredients and provide an understanding of their inherent control release mechanism in the GIT.