About the Sterilization of Chitosan Hydrogel Nanoparticles

Abstract

In the last years, nanostructured biomaterials have raised a great interest as platforms for delivery of drugs, genes, imaging agents and for tissue engineering applications. In particular, hydrogel nanoparticles (HNP) associate the distinctive features of hydrogels (high water uptake capacity, biocompatibility) with the advantages of being possible to tailor its physicochemical properties at nano-scale to increase solubility, immunocompatibility and cellular uptake. In order to be safe, HNP for biomedical applications, such as injectable or ophthalmic formulations, must be sterile. Literature is very scarce with respect to sterilization effects on nanostructured systems, and even more in what concerns HNP. This work aims to evaluate the effect and effectiveness of different sterilization methods on chitosan (CS) hydrogel nanoparticles. In addition to conventional methods (steam autoclave and gamma irradiation), a recent ozone-based method of sterilization was also tested. A model chitosan-tripolyphosphate (TPP) hydrogel nanoparticles (CS-HNP), with a broad spectrum of possible applications was produced and sterilized in the absence and in the presence of protective sugars (glucose and mannitol). Properties like size, zeta potential, absorbance, morphology, chemical structure and cytotoxicity were evaluated. It was found that the CS-HNP degrade by autoclaving and that sugars have no protective effect. Concerning gamma irradiation, the formation of agglomerates was observed, compromising the suspension stability. However, the nanoparticles resistance increases considerably in the presence of the sugars. Ozone sterilization did not lead to significant physical adverse effects, however, slight toxicity signs were observed, contrarily to gamma irradiation where no detectable changes on cells were found. Ozonation in the presence of sugars avoided cytotoxicity. Nevertheless, some chemical alterations were observed in the nanoparticles.

Lawsone-loaded Niosome and its antitumor activity in MCF-7 breast Cancer cell line: a Nano-herbal treatment for Cancer

“…High and negative zeta potential values are an indication of stable preparations and prevent aggregation phenomena [47). PDI parameter approved homogeneity of our suspension that values of less than 0.3 corresponded to a single, rather than a sharp peak, in the DLS profile [48]. In the case of our samples, a single and homogeneous population was detected, except for bare niosome.…”

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

“…Thus, it is necessary to find better sterilization conditions that do not modify the physicochemical properties of the NP. Even the sterilization efficacy of low doses of gamma irradiation (8 and 13 kGy) has been demonstrated [20] in the presence of some protective sugars such as glucose and mannitol at 5% in chitosan hydrogel-NP. Usually, the presence of cryoprotective agents is in considerable quantities in the final batches of NP, so it is reasonable to consider an additional effect of that excipient.…”

Sterilized chitosan‐based composite hydrogels: Physicochemical characterization and in vitro cytotoxicity

“…The steam sterilization method is easy to use, low‐cost, nontoxic, and environmentally friendly (Shamekhi et al, ). However, the temperature applied during steam sterilization frequently has adverse effects on the physicochemical, mechanical, and biological properties of the hydrogels (Galante et al, ; Yu‐Min, Ya‐Hong, Xiao‐Hua, Fei, & Xiao‐Song, ; Zang et al, ). Ji and Shi () observed that steam sterilization impacted the physicochemical and mechanical properties such as porosity, swelling, compressive modulus, and biocompatibility of freeze‐dried chitosan scaffolds.…”