*Article* **Effects of Gamma Radiation on the Sterility Assurance, Antibacterial Ability, and Biocompatibility of Impregnated Hydrogel Macrosphere Protein and Drug Release**

**Po-Sung Fu 1,2, Jen-Chyan Wang 1,3,4, Pei-Ling Lai <sup>3</sup> , Shih-Ming Liu <sup>5</sup> , Ya-Shun Chen <sup>5</sup> , Wen-Cheng Chen 4,5,\* and Chun-Cheng Hung 1,3,4,\***


**Citation:** Fu, P.-S.; Wang, J.-C.; Lai, P.-L.; Liu, S.-M.; Chen, Y.-S.; Chen, W.-C.; Hung, C.-C. Effects of Gamma Radiation on the Sterility Assurance, Antibacterial Ability, and Biocompatibility of Impregnated Hydrogel Macrosphere Protein and Drug Release. *Polymers* **2021**, *13*, 938. https://doi.org/10.3390/ polym13060938

Academic Editor: Bramasta Nugraha

Received: 17 February 2021 Accepted: 14 March 2021 Published: 18 March 2021

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**Abstract:** Devices and medicines used in the medical field must be sterile. Gamma (γ)-irradiation is commonly used for sterilization because its high rate of penetration ensures uniform sterilization. To confirm that hydrogel macrosphere carriers inherit excellent liquid absorption with no cytotoxicity after γ-irradiation sterilization, investigating whether the physiochemical properties of hydrogel macrospheres differ before and after sterilization is essential. The present study evaluated the influence of the recommended 25-kGy γ-irradiation dose on the physicochemical characteristics and in vitro release of bovine serum albumin and vancomycin (an antibiotic medication) from alginate/gelatin with a *w*/*w* ratio of 1/4 crosslinking gel macrospheres. Gel macrosphere properties before and after sterilization were compared according to optical and scanning electron microscopy, infrared spectroscopy analysis, the amino residual crosslinking index, water absorption, degradation, sterility assurance, in vitro drug release, antibacterial ability, and cytotoxicity. The crosslinking index was almost unchanged; however, the γ-irradiation caused in situ hydrogel debonding and recrosslinking, which led to a decrease in the water absorption and increase in the degradation rate of the macrospheres after immersion. The release of gel macrospheres carrying vancomycin did not significantly affect antibacterial ability or biocompatibility after γ-irradiation. Accordingly, we conclude that γ-irradiation is suitable for macrospherical formulation.

**Keywords:** hydrogels; crosslinking; degradable; gamma (γ)-irradiation; sterilization; sterility assurance; antibacterial ability
