Sterilization Procedure for Temperature-Sensitive Hydrogels Loaded with Silver Nanoparticles for Clinical Applications

Diana Rafael, Fernanda Andrade, Francesc Martinez-Trucharte, Jana Basas,
Joaquín Seras-Franzoso , Marta Palau  Xavier Gomis, Marc Pérez-Burgos ,
Alberto Blanco, Alba López-Fernández, Roberto Vélez, Ibane Abasolo,
Màrius Aguirre, Joan Gavaldà, and Simó Schwartz Jr.

Nanomaterials 2019, 9, 380; doi:10.3390/nano9030380

https://www.mdpi.com/2079-4991/9/3/380

Abstract:

Hydrogels (HG) have recognized benefits as drug delivery platforms for biomedical
applications. Their high sensitivity to sterilization processes is however one of the greatest challenges
regarding their clinical translation. Concerning infection diseases, prevention of post-operatory
related infections is crucial to ensure appropriate patient recovery and good clinical outcomes. Silver
nanoparticles (AgNPs) have shown good antimicrobial properties but sustained release at the right
place is required. Thus, we produced and characterized thermo-sensitive HG based on Pluronic®
F127 loaded with AgNPs (HG-AgNPs) and their integrity and functionality after sterilization by
dry-heat and autoclave methods were carefully assessed. The quality attributes of HG-AgNPs were
seriously affected by dry-heat methods but not by autoclaving methods, which allowed to ensure
the required sterility. Also, direct sterilization of the final HG-AgNPs product proved more effective
than of the raw material, allowing simpler production procedures in non-sterile conditions. The
mechanical properties were assessed in post mortem rat models and the HG-AgNPs were tested
for its antimicrobial properties in vitro using extremely drug-resistant (XDR) clinical strains. The
produced HG-AgNPs prove to be versatile, easy produced and cost-effective products, with activity
against XDR strains and an adequate gelation time and spreadability features and optimal for in situ
biomedical applications.