# The Influence of Ionizing Radiation on Paclitaxel-Loaded Nanoparticles Based on PLGA
## 4 Conclusions  
In this study, we demonstrate the feasibility of the radiation sterilization of PLGA nanoparticles containing PTX. Importantly, the polymer matrix synthesized in this study and used as the drug carrier was neither cyto- nor genotoxic, which is required in the case of biomedical applications. The influence of irradiation was analyzed to develop nanoparticles and the polymer matrix itself, and the type of ionizing radiation (\(\gamma\)-rays or EB). Considering the polymer matrix, PLGA exhibited a noticeable degradation degree, given as a decrease in \(M_{\text{n}}\), reaching approx. 14% after irradiation with \(\gamma\)-rays and EB. This result suggests that the main mechanism taking part during the irradiation of PLGA was chain scission. However, the structural changes differed depending on the type of ionizing radiation applied. Gamma-irradiation significantly affected the micro- and macroscopic properties of PLGA by shortening lactidyl segments in the polymer chains. While only negligible changes in characteristic temperatures of the polymer (\(T_{\text{g}}\), \(T_{\text{c}}\), \(T_{\text{m}}\)) were observed, the crystallite content decreased from 35.1% to 22.7%. Contrary to irradiation with \(\gamma\)-rays, in the case of the polymer irradiated with EB, a slight elongation of lactidyl blocks was observed. This may be explained by differences in the course of radiation processes. Considering the polymer irradiated with \(\gamma\)-rays, the changes of properties may be assigned  
Figure 5: The influence of irradiation on kinetic profiles of PTX release from PLGA nanoparticles. with the predominance of chain scission (probably accompanied to some extent by cross-linking), while during irradiation with EB, two processes, that differ in the mechanism of action (chain scission and cross-linking) were likely to occur to a similar extent. While prolonged exposure of the polymer to \(\gamma\)-rays leads to the breakage of polymer chains and the oxidative degradation of the material. In the case of EB, the rapid irradiation of the polymer with a high dose (compared to \(\gamma\)-rays) disables oxygen diffusion into the internal layers of the material. It creates similar conditions as the inert gas atmosphere. As a result, external layers of the polymer undergo oxidative degradation, while crosslinking occurs inside the polymer matrix [32]. This may, therefore, explain the overall decrease in \(M_{\text{n}}\) in the case of both types of irradiation and the elongation of lactidyl blocks of PLGA irradiated with EB. Comparing the effects of the sterilization process with \(\gamma\)-rays and EB on the physicochemical, structural, and thermal properties of PLGA clearly indicates that within this study, EB induced less structural damage to the copolymer. The nanoparticles were obtained with a high efficiency of PTX encapsulation (_EE_ = 94.2 \(\pm\) 3.0%). The particles characterize a spherical shape and an average size of 253.5 \(\pm\) 3.9 nm (shown by DLS). The physicochemical analysis of the particles did not reveal any changes in their size and morphology after the sterilization process. A complete release of PTX was achieved within the first 36 days of the study. The nanoparticles released the drug with a first-order kinetic profile and with non-Fickian diffusion (anomalous mechanism). Importantly, the sterilization process (independent of the type of ionization) did not significantly affect the drug's release. The overall results have shown that PLGA nanoparticles have potential for the sustained delivery of PTX and have proved the great potential of EB for the purposes of sterilization of PLGA-based nanoparticles containing PTX. I.M.D. : conceptualization, chemical, structural, analytical and pharmaceutical research, methodology, investigation, formal analysis and writing--original draft; R.F. : biological research, methodology and investigation; A.Z. : DSC measurement and analysis; K.C.