Release of Doxorubicin from Polyamidoamine-Based Nanoparticles: Mechanism and Kinetic Modelling

Background and Aims: This study aimed to evaluate the release kinetics and mechanism of doxorubicin (DOX)-loaded polyamidoamine (PAA)-based nanoparticles to discover the most suitable kinetic model for describing the drug release behaviour.Methods: Release profiles of 12 distinctive DOX-loaded PAA-based nanoparticles were obtained by conducting an in vitro release study over 48 hours at pH 7.4 and 5.5. The data were fitted to six kinetic models: zero-order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Peppas-Sahlin, and Weibull to assess their applicability. Suitability of models was evaluated on parameters, i.e., regression coefficients (R2), average Akaike information criterion (AIC), and corrected Akaike information criterion (AICc). The mechanism inferred from kinetic fitting was described by the release exponent (n) in the Korsmeyer-Peppas model, the k1, k2, and m parameters in the Peppas-Sahlin model, and the scale (α) and shape (β) parameters in the Weibull model.Results: The Weibull model provided the best fit, with R2 values ranging from 0.971 to 0.998 and AIC values between 40.534 and 71.328. The Peppas-Sahlin model also presented a strong correlation (R2 = 0.885–0.995; AIC = 48.810 to 94.213), while the Korsmeyer-Peppas model exhibited the best fit for initial release (R2 = 0.980–1.000; AIC = −12.055 to 12.043). The exploration of release exponents specified a mixed diffusion mechanism, confirming that drug release was governed by both diffusion and polymer relaxation/erosion.Conclusion: The Weibull model, due to its ability to precisely describe complex release kinetics, was found to be the most suitable kinetic model for explaining DOX release from PAA-based nanoparticles. The release mechanism involved both diffusion and polymer relaxation, emphasizing the adaptability of PAAbased nanoparticles for controlled drug delivery applications.