# The Influence of Ionizing Radiation on Paclitaxel-Loaded Nanoparticles Based on PLGA
## 1 Introduction  
Cancer is a leading cause of death worldwide. According to the World Health Organization (WHO), the most common cancer types in 2020 were breast and lung cancer. Although breast cancer is characterized by a high cure rate when detected early, lung cancer was the most common cause of cancer deaths in 2020 (1.8 million deaths) [1]. It is, therefore,of great importance to provide new solutions and new drug forms for anticancer therapy in combination with drug substances already placed on the market. Paclitaxel is a potent anticancer agent of natural origin that was originally isolated from year bark (_Taxus brevifolia_). PTX is widely used in anticancer therapy, namely, in the treating of breast, ovarian, and non-small cell lung cancers, along with malignant melanoma and leukemias [2; 3]. However, its low aqueous solubility is challenging considering the method of administration. For this reason, the entrapment of PTX into nanoparticulate systems has been extensively studied. Polymeric nanospheres reduce the side effects of cytostatics, enhance their tumor deposition and improve therapeutic efficacy. The advantage of DDSs over traditional drug forms results from controlled and sustained drug release in the body [4]. The most desirable drug carriers are obtained from biodegradable and biocompatible polyesters. These polymers, when introduced to the organism, are metabolically decomposed into completely removable and non-toxic products. Nevertheless, polymer drug carriers administered parenterally, are required to withstand the harsh conditions of the sterilization process. Considering biodegradable polyester drug carriers, the assurance of sterility is particularly challenging. Polyesters are thermally unstable; therefore, the number of potentially available sterilization methods is limited, mainly to aseptic filtration. The assurance of sterility under this method is very costly and demanding, and most importantly, for sterile filtration, membranes of a max. 0.22 um pore size are recommended for use [5]. This, in turn, limits the use of this method in relation to particles size. Moreover, sterile filtration may be questioned from the safety point of view due to feasible microbiological contamination. Therefore, it is of great interest to find an effective, alternative method to enable the maintenance of sterility criteria without altering the physicochemical properties of the sterilized material. Among other commonly used sterilization methods are dry-heat, ionizing radiation, steam, the use of chemicals, and UV. Due to high temperatures applied, dry-heat and steam are excluded for heat- and moisture-sensitive polyester-based materials. High temperatures used in the sterilization process may alter the physicochemical and mechanical properties of polymer matrix and consequently alter the kinetic profile of drug release. Recently, [PERSON] et al. [6] presented preliminary studies on the use of UV and gamma photons for the sterilization of PLGA nanoparticles. They indicated that the use of UV can be an effective sterilization procedure and, at the same time, not cause significant changes in the physicochemical parameters of nanoparticles. However, the penetration depth of UV rays is very low [7] and therefore is limited mainly to surfaces and transparent scaffolds. The use of chemicals, such as gaseous ethylene oxide, or other highly volatile substances such as formaldehyde, may be applicable for heat- and moisture-sensitive materials. However, some harmful residues may remain within the polymer matrix [8]. Furthermore, using chemicals may alter the polymer's physicochemical properties by reacting with its functional groups [9]. On the other hand, ionizing radiation is the method of choice, gaining an increasing interest of scientists for terminal sterilization of DDSs. The use of the pharmacopeial recommended dose, 25 kGy, is considered adequate for sterilizing purposes [5; 10; 11; 12; 13].