Effect of UV and Gamma Irradiation Sterilization Processes in the Properties of Different Polymeric Nanoparticles for Biomedical Applications

Abstract

The sterilization processes of nanoparticles (NP) by autoclaving and filtration are two of the most utilized methods in the pharmaceutical industry but are not always a viable option. For this reason, the search for alternative options such as UV and gamma radiation is of interest. In this work, we evaluated both types of sterilization on two types of NP in solid state widely employed in the literature for biomedical applications, poly-(ε-caprolactone) and poly(d,l-lactide-co-glycolide) acid NP stabilized with polyvinyl alcohol. Physicochemical properties and cell viability were studied pre-and post-sterilization. The efficiency of irradiation sterilization was performed by a test of sterility using 1 × 10 8 CFU/mL of Escherichia coli, Staphylococcus aureus, and Candida albicans. Microbiological monitoring revealed that both methods were sufficient for sterilization. After the UV irradiation sterilization (100 µJ/cm 2 ), no substantial changes were observed in the physicochemical properties of the NP or in the interaction or morphology of human glial cells, though 5 and 10 kGy of gamma irradiation showed slight changes of NP size as well as a decrease in cell viability (from 100 µg/mL of NP). At 5 kGy of radiation doses, the presence of trehalose as cryoprotectant reduces the cell damage with high concentrations of NP, but this did not occur at 10 kGy. Therefore, these methods could be highly effective and low-processing-time options for sterilizing NP for medical purposes. However, we suggest validating each NP system because these generally are of different polymer-composition systems.

Insights into Terminal Sterilization Processes of Nanoparticles for Biomedical Applications

“…The formation of free radicals can affect all the biological applications of the nanoparticles. Changes in the matrix polymers would be less significant, although it depends on the amount of energy supplied and the nanoparticle’s composition [ 64 ]. Concerning this, FTIR could evidence changes in the stabilizer’s backbone.…”

“…The operating range in kGy emission is limited for each material and type of nanoparticle. When the energy supplied is higher than that necessary to sterilize, the undesirable side effects produced by sterilization by gamma radiation are similar to UV but with a greater magnitude [ 64 ]. Materials external to the nanoparticle are more susceptible to modifications.…”

“…On the other hand, terminal sterilization can also be applied to lyophilized products, minimizing the absorbing effect of heat or radiation by water on the materials. The presence of cryoprotectants in lyophilized products can also protect against radiation phenomena and minimize the possible changes in the nanoparticles’ physical, chemical, and biological effects [ 64 ].…”

“…Similarly, in 2020, Tapia-Guerrero et al [ 64 ] performed a concise investigation about the modifications triggered by UV radiation on two different polymeric nanosystems. Nanoparticles based on PCL and poly-( d , l -lactic-co-glycolic) acid (PLGA) stabilized by PVA were obtained by the emulsion–diffusion method.…”

“… At 5 kGy of radiation doses, the presence of trehalose as cryoprotectant reduced the cell damage with high concentrations of nanoparticles, but this did not occur at 10 kGy. [ 64 ] Ciprofloxacin HCl-loaded poly( d , l -lactide-glycolide) nanoparticles 226.1 ± 1.30 Gamma irradiation (cobalt-60 with a dose of 25 kGy) No significant differences in the particle size and the gamma-sterilized formulations’ zeta potential value compared with non-sterilized samples. Reconstitution after gamma-sterilization appeared to be more difficult than before sterilization for all formulations studied.…”