# The Influence of Ionizing Radiation on Paclitaxel-Loaded Nanoparticles Based on PLGA
## 3 Results and Discussion
### In Vitro Drug Release  
Figure 5 displays cumulative drug release profiles of irradiated and non-irradiated nanoparticle formulations. The release profile of free PTX was added as a control. The release of PTX from PLGA nanoparticles exhibited a monophasic release pattern (no initial burst release was observed). An almost complete drug release was observed after 36 days of the study, independent of applied irradiation. Importantly, the release of free drug was faster compared to the drug release from the nanoparticles. This indicates that the release profiles of the encapsulated drug were not hindered by the dialysis membrane. The in vitro release mechanism of paclitaxel from the nanoparticles was further evaluated using zero-order, first-order, Higuchi and Korsmeyer-Peppas mathematical release kinetic models (Table 6). Figure 3: HPLC chromatograms of PTX extracted from the nanoparticles (**a**) non-irradiated (\(\text{C}_{\text{PTX}}\) = 7.6 \(\upmu\)g mL\({}^{-1}\)), (**b**) \(\gamma\)-irradiated (\(\text{C}_{\text{PTX}}\) = 5.6 \(\upmu\)g mL\({}^{-1}\)) and (**c**) irradiated with EB (\(\text{C}_{\text{PTX}}\) = 7.8 \(\upmu\)g mL\({}^{-1}\)). \begin{table}
\begin{tabular}{c c c c} \hline \hline
**Irradiation** & \
\begin{tabular}{c} **Size** \\ **(nm)** \\ \end{tabular} & **PDI** &
\begin{tabular}{c} **ZP** \\ **(mV)** \\ \end{tabular} \\ \hline PLGA & 253.6 \(\pm\) 4.1 & 0.19 \(\pm\) 0.03 & \(-\)22.48 \(\pm\) 0.41 \\ \hline PLGA-PTX & 253.5 \(\pm\) 3.9 & 0.17 \(\pm\) 0.03 & \(-\)20.83 \(\pm\) 1.17 \\ \hline PLGA-PTX & 256.4 \(\pm\) 3.1 & 0.20 \(\pm\) 0.02 & \(-\)36.73 \(\pm\) 1.26 \\ irr-\(\gamma\) & 253.6 \(\pm\) 2.1 & 0.17 \(\pm\) 0.02 & \(-\)33.75 \(\pm\) 0.57 \\ \hline \hline \end{tabular}
\end{table} 
Table 5: The influence of ionizing radiation on PTX-loaded nanoparticles determined by DLS. The values of R\({}^{2}\) for zero-order and first-order kinetics suggest that the drug release profiles from the PLGA nanoparticles followed the first-order kinetic, regardless of irradiation. Some references, as, e.g., the work of [PERSON] et.al. [36], demonstrate the zero-order release of paclitaxel from PLGA nanoparticles, and being well characterized by Korsmeyer-Peppas model. However, mathematical models are only a simplification and do not give exact insight into the mechanism of drug release. Moreover, the composition of the comonomers obtained by us is different from those tested by other authors. It should also be noted that the obtained R\({}^{2}\) values for the zero-order and first-order kinetics models are not very different. Probably, in the case of the obtained nanoparticles, we are dealing with a mixed drug release mechanism. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Irradiation**} & \multicolumn{2}{c}{**Zero-Order**} & \multicolumn{2}{c}{**First-Order**} & \multicolumn{2}{c}{**Higuchi**} & \multicolumn{2}{c}{**Korsmeyer–Peppas**} \\ \cline{2-7}  & **R\({}^{2}\)** & **R\({}^{2}\)** & **R\({}^{2}\)** & **K\({}_{\text{H}}\)****a** & **R\({}^{2}\)** & **n\({}^{\text{b}}\)** \\ \hline
**non-irr** & 0.881 & 0.998 & 0.981 & 17.805 & 0.995 & 0.793 \\ \hline
**irr-\(\gamma\)** & 0.949 & 0.963 & 0.991 & 17.906 & 0.977 & 0.857 \\ \hline
**irr-e** & 0.946 & 0.974 & 0.995 & 17.820 & 0.993 & 0.857 \\ \hline \hline \end{tabular}  
\end{table} 
Table 6: Data analysis of PTX release from PLGA nanoparticles. Figure 4: SEM micrographs of lyophilized PLGA nanoparticles: (**a**) placebo, (**b**) non-irr, (**c**) irr-\(\gamma\) and (**d**) irr-e PLGA nanospheres with PTX. Additionally, the release data fitted well to the Higuchi and Korsmeyer-Peppas mathematical models. A detailed analysis of the release exponent \(n\) from the Korsmeyer-Peppas model (\(n_{\text{non-irr}}=0.79\) and \(n_{\text{irr-\gamma,EB}}=0.86\)) indicates drug release with non-Fickian diffusion (\(0.45<n<0.89\)), in which two mechanisms (diffusion and erosion) take part in drug release [37].