*2.6. Statistical Analysis*

Statistical analysis was performed using GraphPad Prism 8 (version 8.1.1; GraphPad Software, Inc., San Diego, CA, USA). Mean ± SD values were calculated for all results. Further statistical significance was assessed, adopting the two-tailed paired t-tests (\*\* *p* ≤ 0.01; \*\*\*\* *p* ≤ 0.0001). Cumulative releases were split into phases, and each fitted by a first-order polynomial (MATLAB® polyfit, MathWorks, Natick, MA, USA). Slopes of cumulative release curves were normalized and displayed as a percentage of the passive release profiles.

## **3. Results and Discussion**
