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Cited by 25Hydrogels: synthesis, properties, applicationsAdvanced Drug Delivery SystemsCollagen: Extraction and Characterization

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

Open access
Fu, Po-Sung, Wang, Jen-Chyan, Lai, Pei-Ling, Liu, Shih-Ming, Chen, Ya-Shun, Chen, Wen-Cheng, Hung, Chun-Cheng·2021·Polymers
DOI 10.3390/polym13060938PMC PMC8003089
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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.

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Figure A1 Full and specific absorption bands were obtained through the ATR spectrum analysis of macrospheres before (HyS-w/o γ) and different γ-radiation kGy after (HyS-w/γ) sterilization.
Figure A1 Full and specific absorption bands were obtained through the ATR spectrum analysis of macrospheres before (HyS-w/o γ) and different γ-radiation kGy after (HyS-w/γ) sterilization.CC BY · PubMed Central
Figure A2 (a) Quantitative and (b) qualitative (n = 6) cytotoxicity test results of hydrogel macrosphere extract cultured with L929 cells for 24 h.
Figure A2 (a) Quantitative and (b) qualitative (n = 6) cytotoxicity test results of hydrogel macrosphere extract cultured with L929 cells for 24 h.CC BY · PubMed Central
Figure 1 Freeze-dried hydrogel macrospheres after (HyS-w/γ) and before (HyS-w/o γ) sterilization of internal macrosphere microstructures of (a) photographs, (b) OM images, and (c) SEM images.
Figure 1 Freeze-dried hydrogel macrospheres after (HyS-w/γ) and before (HyS-w/o γ) sterilization of internal macrosphere microstructures of (a) photographs, (b) OM images, and (c) SEM images.CC BY · PubMed Central
Figure 2 Comparisons of the (a) pore size distribution, (b) average pore size (n = 60; *: p < 0.05), and (c) porosity of hydrogel macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization (n = 60; #: p > 0.05).
Figure 2 Comparisons of the (a) pore size distribution, (b) average pore size (n = 60; *: p < 0.05), and (c) porosity of hydrogel macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization (n = 60; #: p > 0.05).CC BY · PubMed Central
Figure 3 (a) Full and specific absorption bands obtained through the FTIR spectrum analysis of macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization. (b) Schematic of the mechanisms of amide bond decomposition into active imine or nitrile groups after irradiation, which can generate new intermolecular crosslinking sites in hydrogels.
Figure 3 (a) Full and specific absorption bands obtained through the FTIR spectrum analysis of macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization. (b) Schematic of the mechanisms of amide bond decomposition into active imine or nitrile groups after irradiation, which can generate new intermolecular crosslinking sites in hydrogels.CC BY · PubMed Central
Figure 4 Physiochemical analysis of hydrogel macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization corresponds to amine fixation index (n = 6, #: p > 0.05) (a), water absorption ratio (n = 10) (b), and degradation rate (n = 10) (c).
Figure 4 Physiochemical analysis of hydrogel macrospheres before (HyS-w/o γ) and after (HyS-w/γ) sterilization corresponds to amine fixation index (n = 6, #: p > 0.05) (a), water absorption ratio (n = 10) (b), and degradation rate (n = 10) (c).CC BY · PubMed Central
Figure 5 Bacterial endotoxin results of sterilized hydrogel macrospheres (NC: negative control; PC: positive control; PPC: positive product control; 2×, 4×, 8×, and 16× indicate extracts diluted with pyrogen-free water).
Figure 5 Bacterial endotoxin results of sterilized hydrogel macrospheres (NC: negative control; PC: positive control; PPC: positive product control; 2×, 4×, 8×, and 16× indicate extracts diluted with pyrogen-free water).CC BY · PubMed Central
Figure 6 Protein release of BSA before (HyS-w/o γ) and after (HyS-w/γ) sterilization of hydrogel macrospheres in vitro (n = 10) (a) and cumulative antibiotic release of hydrogel macrospheres impregnated with vancomycin after sterilization (HyS-Van25, n = 10) (b).
Figure 6 Protein release of BSA before (HyS-w/o γ) and after (HyS-w/γ) sterilization of hydrogel macrospheres in vitro (n = 10) (a) and cumulative antibiotic release of hydrogel macrospheres impregnated with vancomycin after sterilization (HyS-Van25, n = 10) (b).CC BY · PubMed Central
Figure 7 (a) Qualitative analysis of the sterility assurance of hydrogel macrospheres after sterilization (HyS-w/γ). (b) Qualitative results of the disk diffusion antibacterial effect of hydrogel macrospheres impregnated with vancomycin (HyS-Van25, n = 3) against E. coli and S. aureus after 24 h of interaction. Right figures indicate the inhibitory zones formed by the presence of macrospheres with a diameter of 6 mm. (c) Quantitative antibacterial results of hydrogel macrospheres impregnated with vancomycin after irradiation (HyS-Van25, n = 3) against E. coli and S. aureus after 24 h of interaction under broth dilution.
Figure 7 (a) Qualitative analysis of the sterility assurance of hydrogel macrospheres after sterilization (HyS-w/γ). (b) Qualitative results of the disk diffusion antibacterial effect of hydrogel macrospheres impregnated with vancomycin (HyS-Van25, n = 3) against E. coli and S. aureus after 24 h of interaction. Right figures indicate the inhibitory zones formed by the presence of macrospheres with a diameter of 6 mm. (c) Quantitative antibacterial results of hydrogel macrospheres impregnated with vancomycin after irradiation (HyS-Van25, n = 3) against E. coli and S. aureus after 24 h of interaction under broth dilution.CC BY · PubMed Central
Figure 8 (a) Quantitative cell viability (n = 6) and (b) qualitative cell morphologies of L929 cells cultured for 24 h in a solution of hydrogel macrospheres impregnated with vancomycin after sterilization (HyS-Van25).
Figure 8 (a) Quantitative cell viability (n = 6) and (b) qualitative cell morphologies of L929 cells cultured for 24 h in a solution of hydrogel macrospheres impregnated with vancomycin after sterilization (HyS-Van25).CC BY · PubMed Central

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Research works printed but not linked: 2

  1. Peppas, N.A. (2010). Biomedical Applications of Hydrogels Handbook, Springer Science & Business Media.
  2. Lowman, A., and Peppas, N. (1999). Encyclopedia of Controlled Drug Delivery, John Wiley & Sons.

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Metadata

Authors
Fu, P.-S., Wang, J.-C., Lai, P.-L., Liu, S.-M., Chen, Y.-S., Chen, W.-C., & Hung, C.-C.
Affiliations
  • Kaohsiung Medical University (TW)
  • Kaohsiung Medical University Chung-Ho Memorial Hospital (TW)
  • Feng Chia University (TW)
Corresponding author
  • Chen, Wen-Cheng
  • Hung, Chun-Cheng
ORCID
Venue
Polymers
Publisher
MDPI AG
Published
2021-03-18
Volume
13
Issue
6
Pages
938
ISSN
2073-4360 (ISSN-L)
DOI
10.3390/polym13060938
PMC
PMC8003089
OpenAlex
W3136826041
Cited by
25
References
54
Citations by year
2026: 2 · 2025: 5 · 2024: 3 · 2023: 8 · 2022: 5 · 2021: 2
FWCI
1.43
Type
journal article
Language
en
Open access
Licence
Locations
  • Polymers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • the Southern Taiwan Science Park Bureau, Ministry of Science and Technology, Taiwan (107CB02)
  • Kaohsiung Municipal Ta-Tung Hospital plan (kmtth-109-040)
  • Ministry of Science and Technology, Taiwan (108-2745-8-035-003 -)
Topics
  • Physical Sciences › Materials Science › Biomaterials › Hydrogels: synthesis, properties, applications
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
Keywords
gamma irradiation sterilization, bovine serum albumin, vancomycin, in vitro drug release, antibacterial activity, biocompatibility, water absorption, hydrogel degradation, cytotoxicity, protein drug delivery

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