Design and use of silica-containing redox nanoparticles, siRNPs, for high-performance peritoneal dialysis

Abstract

The prevention of encapsulating peritoneal sclerosis (EPS) and the enhancement of dialysis efficiency are two important strategies that can improve the quality of life of patients undergoing peritoneal dialysis. We have thus far developed bionanoparticles that effectively scavenge reactive oxygen species (redox nanoparticles; RNPs). The objective of this study was to apply RNPs as a component of dialysate to reduce oxidative stress. Porous silica nanoparticles were combined with RNPs to enhance the effective adsorption capacity of low-molecular weight (LMW) compounds. The silica-containing RNPs (siRNPs) were confirmed to statistically decrease the level of creatinine and blood urea nitrogen in vivo. EPS model rats that underwent an intraperitoneal injection of chlorhexidine gluconate exhibited dysfunction of the peritoneal membrane. siRNP administration did not result in dysfunction of the peritoneal membrane. An LMW nitroxide compound, TEMPOL, also showed a weak peritoneal protective effect, although its efficiency was limited. No blood uptake of siRNPs was observed when they were administered into the peritoneal cavity. However, LMW-TEMPOL diffused into the blood stream, which might have decreased its effective concentration in the peritoneal cavity and led to adverse effects across the entire body. Considering these results, siRNPs are expected to be a new multi-functional nanomaterial for high performance peritoneal dialysis.

Liposome and Polysaccharide Based Nanomedicines: An Emerging Hope to Improve the Peritoneal Dialysis Technique

“…There are several reports in the literature now where nanotechnology products including nanomedicines have been implicated in the diagnosis and treatment of kidney diseases [6]. There is also an increasing cohort of nanomaterials which has been envisaged to improve the PD technique either through the use of (a) antimicrobial spray for preventing Catheter Exit-Site Infection [7], (b) liposomes for detoxification of drugs and endogenous metabolites to enhance the efficiency of peritoneal dialysis [8,9], (c) nano-carriers for TNF-β1-SiRNA to inhibit the peritoneal fibrosis [10], (d) silicacontaining redox nanoparticles (siRNPs) for high-performance peritoneal dialysis through suppressing oxidative stress by scavenging Reactive Oxygen Species [11], and (e) antimicrobial nanomaterials synthesized biologically-which confer several advantages like biocompatibility, low cellular toxicity and activity against variety of drug-resistant bacteria-to impart infection resistant properties to the PD fluid and thus reducing the frequency of PD associated infections [12]. An alternative, but more relevant and promising approach to improve the existing PD therapy-in terms of its dialysis efficiency and limiting microbial infections-can be envisaged based on the use of liposomal antibiotic formulations [13,14].…”

Development of silica-containing redox nanoparticles for medical applications

“…In the first method, siRNP(1) are prepared by the pH-sensitive self-assembly of PEG-b-PMNT where the colloidal silica (Snow-Tech-O, Nissan Chemical Industries) is added to an aqueous solution of PEG-b-PMNT under acidic conditions, after which the pH is raised. 27 In the second method, siRNP(2) are prepared by the dialysis of a dimethyl sulfoxide (DMSO) solution containing PEG-b-PMNT and suspended silica nanoparticles (MEK-ST-40, Nissan Chemical Industries) against water. 28 In these cases, the negatively charged silica nanoparticles are entrapped in the positively charged RNP N core.…”

“…In the third method, siRNP(3) are prepared by a sol-gel reaction of tetraethyl orthosilicate (TEOS) in the RNP N core. 27,28 During this process, hydrophobic TEOS is solubilized in the polyamine core of the RNP N due to the hydrophobic interaction, then subsequently hydrolyzed by the secondary amino groups in the RNP N core. Unstable intermediates are then condensed to form silica nanoparticles.…”

“…In fact, 4-hydroxy-TEMPO (TEMPOL) is absorbed into the bloodstream, which decreases its effective concentration in the peritoneal cavity and leads to adverse effects, such as a dramatic reduction in blood pressure. 27 Since the siRNP are approximately 40-45 nm in diameter, they remain within the intraperitoneal area and continuously scavenge ROS (see Fig. 2A).…”

Redox nanoparticles: synthesis, properties and perspectives of use for treatment of neurodegenerative diseases

“…Electrostatic interactions between the cationic segment of a polymer in the core and the entrapped silica nanoparticles form a crosslinked structure that provides siRNP stability in vivo, even under harsh conditions in the gastrointestinal tract. Si-RNPs can be applied not only as adsorbents of body wastes, but also as drug carriers with high loading capacity due to their excellent adsorption properties [ 40 ].

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