Release Kinetics Of Nanoparticles Research Articles

Wound Dressing Produced by Electrospinning Fibrous Material Based on Poly(Vinyl Alcohol) and Ce Compounds

Electrospinning of fibrous bandage material based on poly(vinyl alcohol) containing CeO2 nanoparticles was investigated. Medical and biological effects of Ce compounds on post-burn scartissue deformation were assessed experimentally. The release kinetics of nanoparticles from the fibrous material were studied. The results demonstrated that use of fibrous materials containing CeO2 nanoparticles (1%) as wound dressings was promising.

Abstract 3899: Nanoparticle reduces hepatotoxicity of cancer treatment by controlled release and Kupffer cell uptake

Abstract Background: One of the major concerns in cancer treatment and clinical translation of many anti-cancer compounds has been their potential toxicities, especially hepatotoxicity. Nanoparticle (NP) holds great potential to solve the problem, as many clinical studies have not shown increased hepatotoxicity for nanotherapeutics with higher accumulation in the liver. However, there are few studies investigating how nanoparticle assists in reducing hepatotoxicity. Herein, we demonstrated that nanoformulation of known hepatotoxic anti-cancer compounds showed lower hepatotoxicity than their small molecule counterparts. Importantly, we demonstrated that slower drug release is associated with reduced hepatotoxicity. We also showed that that Kupffer cell uptake in the liver reduce nanotherapeutics’ hepatotoxicity. Methods: Two different antineoplastic drugs with high hepatotoxicity, SN-38 and wortmannin (Wtmn), were encapsulated into lipid shell-PLGA core nanoparticles separately. NP release kinetics were controlled by adjusting lipids/polymer ratio for fast (Fast-NPs), medium (Medium-NPs) and slow drug release profile (Slow-NPs), respectively. Hepatotoxicity of NPs or free drugs was analyzed by assessing serum ALT and AST levels post intravenous injection at ½ MTD in CD-1 mice. IHC staining of HO-1 and Mn-SOD was also used to show liver damage. In vitro hepatotoxicity of primary hepatocytes after Kupffer cell uptake was assessed by MTS assay and LDH assay. In vivo macrophage depletion was achieved using clodrosome. Results: Nanoformulations of SN-38 and Wtmn showed lower ALT and AST levels than their small molecule counterparts 12 h and 24 h post treatment. The liver damage was further confirmed with IHC staining of Mn-SOD and HO-1. To address the effect of drug release kinetics on hepatotoxicity, we showed that over 90% of drugs were released within 24 h in Fast-NP. While the release rate of Slow-NPs was 66.8% for SN-38 and 67.5% for Wtmn. We showed that Slow-NPs of Wtmn resulted in minimal increase of ALT and AST levels. Compared to the baseline in untreated mice, the ALT level was 2.3-fold for Slow-NPs, 4.4-fold for Medium-NPs and 6-fold for fast-NPs; meanwhile, the AST level was 1.6-fold, 2.5-fold and 3.6-fold, respectively. To assess the effect of Kupffer cell uptake in hepatotoxicity, we found that the toxicity of the nanotherapeutics for primary hepatocytes significantly reduced after Kupffer cell uptake in vitro. We further confirmed it in vivo by depleting Kupffer cells in CD-1 mice. We demonstrated that ALT and AST levels of nanotherapeutics significantly increased to the levels comparable to free drugs after Kupffer cell depletion. Conclusions: We demonstrate that nanoparticle reduces hepatotoxicity of cancer treatment by controlled release and Kupffer cell uptake. Our work bridges an important knowledge in nanoparticle drug delivery and clinical translation of nanomedicine. Citation Format: Yu Mi, Feifei Yang, Andrew Z. Wang. Nanoparticle reduces hepatotoxicity of cancer treatment by controlled release and Kupffer cell uptake [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3899.

Influence of supporting polyelectrolyte layers on the coverage and stability of silver nanoparticle coatings

Deposition mechanisms of citrate-stabilized silver nanoparticles 15nm in diameter on cationic polyelectrolyte supporting layers were evaluated. Initially, the bulk and the electrokinetic properties of cationic polyelectrolytes and their monolayers on mica were determined using in situ streaming potential measurements. Analogously, the size distribution, stability and electrokinetic properties of silver particles were studied using transmission electron microscopy (TEM) and microelectrophoretic measurements. Afterward, the kinetics of silver particle deposition was quantitatively evaluated by a direct enumeration procedure exploiting the atomic force microscopy (AFM) and scanning electron microscopy (SEM) micrographs. Using this method the kinetics of particle adsorption was determined for various polyelectrolyte supporting layers as a function of ionic strength. These experiments were interpreted in terms of the random sequential adsorption (RSA) model. It was found that the highest coverage of 0.35 was obtained for silver monolayers deposited on poly(allylamine hydrochloride) (PAH)-modified mica in the case of higher ionic strength. The release kinetics of nanoparticles was also studied using the SEM and AFM imaging method. Using these experimental data the equilibrium adsorption constant and the binding energy of nanoparticles were calculated by exploiting the RSA approach. The investigations showed that the most stable silver monolayers are obtained for the poly-l-lysine (PLL) supporting layers where the 50% of particle is released after 441h, whereas in the case of PEI the release time was only 9h. These results are consistent with the model of discrete electrostatic interactions among ion pairs. Additionally, the obtained results have practical implication indicating that it is feasible to regulate the rate of silver nanoparticle release by a proper choice of the polyelectrolyte forming the supporting layer.

Polyoctanediol citrate–ZnO composite films: Preparation, characterization and release kinetics of nanoparticles from polymer matrix

In this paper we describe a novel composite material consistent of citric acid-based polyester elastomer and zinc oxide nanoparticles (ZnO NPs). Produced material was characterised by field emission electron microscopy, Fourier-transform infra-red spectroscopy and mechanical tests. Release kinetics of NPs from the polymer matrix and anti-bacterial properties of the composite are also reported. We demonstrate that the composite morphology, mechanical integrity and the relative amount of NPs released under physiological conditions are strongly affected by variation of the initial concentration of NPs in the composite mixture during the fabrication process.

Effect of cryoprotectants on the reconstitution of surfactant-free nanoparticles of poly(DL-lactide-co-glycolide)

Various cryoprotectants were tested to reconstitute the surfactant-free nanoparticles of poly(DL-lactide-co-glycolide) (PLGA). When 2.0% (w/v) of sucrose, trehalose and lactose were used, nanoparticles were completely reconstituted into aqueous solution and particle size was not significantly changed. Above 1.0% (w/v) of sucrose, trehalose and lactose, nanoparticles are well reconstituted whereas it was precipitated with 1.0% (w/v) of mannitol. Drug-encapsulated surfactant-free nanoparticles were quite reconstituted when 2.0% (w/v) of sucrose, trehalose and lactose. Drug release kinetics of nanoparticles was not significantly changed by cryoprotectants.