Search

Colloidal chitosan/tripolyphosphate (TPP) particles have attracted significant attention as potential delivery vehicles for drugs, genes and vaccines. Yet, there have been several fundamental studies that showed these particles to disintegrate at physiological pH and ionic strength levels. To reconcile these findings with the published drug, gene and vaccine delivery research where chitosan/TPP particle disintegration was not reported, it has been postulated that the particles could be stabilized by their bioactive payloads. To test this hypothesis, here we examine whether the association of chitosan/TPP particles with model anionic proteins, α-lactalbumin (α-LA) and bovine serum albumin (BSA), and polynucleotides (DNA) enhances chitosan/TPP particle stability at physiological ionic strengths, using 150 mM NaCl (pH 5.5) and 1× PBS (pH 6.0) as the dissolution media. Light scattering and UV-vis spectroscopy revealed that anionic protein uptake had no impact on particle stability, likely due to the relatively weak protein/particle binding at near-physiological ionic strengths, which caused the protein to be rapidly released. This result occurred regardless of whether the protein was loaded during or after particle formation. Conversely, DNA uptake (at least at some compositions) increased the chitosan fractions persisting in a complexed/particulate form in model dissolution media, with the DNA remaining largely complexed to the chitosan at all investigated conditions. Collectively, these findings suggest that, while most bioactive payloads do not interact with chitosan strongly enough to stabilize chitosan/TPP particles, these chitosan particles can be stabilized to dissolution through the incorporation of polyanions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Submicron particles prepared by complexing chitosan with tripolyphosphate (TPP) attract widespread interest as potential drug, gene and vaccine delivery vehicles, and many published studies examine their release properties. Despite these sustained efforts, however, literature on the release performance of chitosan/TPP micro- and nanoparticles is filled with conflicting results, with some reporting nearly instantaneous release, while others showing the release to be sustained for up to multiple days. To resolve these opposing findings, we recently postulated that the in vitro release profiles obtained from chitosan/TPP particles by the standard "sample and separate" or "solvent replacement" method (where the solvent was periodically replaced with fresh buffer and analyzed for the released bioactive molecule content) may have been subject to strong experimental artifacts and not have reflected their true release behavior. To explore this possibility, here we examine several experimental artifacts that may arise during such in vitro experiments and show that conflicting findings on release from chitosan/TPP particles can arise from: (1) incomplete particle separation from the release media upon centrifugation; (2) irreversible particle coagulation; and (3) failure to maintain sink conditions. Moreover, we show that some of the longer-lasting release profiles may reflect the use of physiologically irrelevant (low-ionic-strength) release media. By analyzing and discussing these effects, this article provides guidelines for obtaining more reliable release profiles for chitosan/TPP micro- and nanoparticles and other/related colloidal carriers., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nanoparticles prepared through the ionotropic gelation of chitosan with tripolyphosphate (TPP) have been extensively studied as vehicles for drug and gene delivery. Though a number of these works have focused on preparing particles with narrow size distributions, the monodisperse particles produced by these methods have been limited to narrow size ranges (where the average particle size was not varied by more than twofold). Here we show how, by tuning the NaCl concentration in the parent chitosan and TPP solutions, low-polydispersity particles with z-average diameters ranging between roughly 100 and 900nm can be prepared. Further, we explore how the size of these particles depends on the method by which the TPP is mixed into the chitosan solution, specifically comparing: (1) single-shot mixing; (2) dropwise addition; and (3) a dilution technique, where chitosan and TPP are codissolved at a high (gelation-inhibiting) ionic strength and then diluted to lower ionic strengths to trigger gelation. Though the particle size increases sigmoidally with the NaCl concentration for all three mixing methods, the dilution method delivers the most uniform/gradual size increase - i.e., it provides the most precise control. Also investigated are the effects of mixture composition and mixing procedure on the particle yield. These reveal the particle yield to increase with the chitosan/TPP concentration, decrease with the NaCl concentration, and vary only weakly with the mixing protocol; thus, at elevated NaCl concentrations, it may be beneficial to increase chitosan and TPP concentrations to ensure high particle yields. Finally, possible pitfalls of the salt-assisted size control strategy (and their solutions) are discussed. Taken together, these findings provide a simple and reliable method for extensively tuning chitosan/TPP particle size while maintaining narrow size distributions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Chitosan/tripolyphosphate (TPP) micro- and nanogels are widely explored as vehicles for protein drug and vaccine delivery. Yet, aside from the consensus that protein uptake into these particles is enhanced by stronger protein/particle binding, factors that control their uptake performance, such as differences in the chitosan, TPP and protein concentrations, remain poorly understood. Here, we show that many of the differences in the reported association efficiencies (AE-values) for protein uptake likely reflect the largely-ignored variability in the particle yield (X Agg ), which is the fraction of the added chitosan that self-assembles into particles and (like the AE) varies with the chitosan, TPP and protein concentrations. Factors affecting X Agg are first systematically explored. The AE is then shown to scale almost linearly with the X Agg (which increases with the TPP and protein-to-chitosan ratios) until all chitosan aggregates into particles. Remarkably, the data collected at variable TPP and protein concentrations collapses onto a single AE∝X Agg curve for each protein type. Further analysis of protein/particle binding reveals this rise in AE with X Agg to reflect: (1) an increase in binding sites within the particles; and (2) a decrease in soluble (non-particulate) chitosan molecules, which form soluble protein/chitosan complexes and compete with the chitosan/TPP particles for the unassociated protein. These findings highlight the need to carefully analyze the effects of formulation parameters on chitosan/TPP particle yields and can likely be extended to other ionically crosslinked colloidal drug carriers., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ionically crosslinked chitosan particles with submicron dimensions attract widespread interest as materials for controlled release. To this end, we have examined the formation and dissolution of nanoparticles prepared by crosslinking chitosan with pyrophosphate (PPi). The formation of these particles required a critical PPi concentration (which increased with the chitosan concentration), and their z-average hydrodynamic diameters could be predictably tuned from roughly 60 to 220 nm by varying the concentration of the parent chitosan solutions. Unlike the nanoparticles crosslinked with the commonly used tripolyphosphate (TPP), which coagulated and precipitated when TPP was in excess, the chitosan/PPi nanoparticles remained colloidally stable even at high PPi concentrations. Moreover, the analysis of their dissolution revealed hysteresis in the particle formation/dissolution cycle, where portions of the crosslinked chitosan/PPi complexes remained stably intact at PPi concentrations below those required for their formation. This irreversible behavior was surmised to reflect the cooperativity of chitosan/PPi binding and was qualitatively modeled using the Bragg-Williams theory., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study focuses on the synthesis and evaluation of carbon−coated Ni−Fe alloy catalysts (NiFex@C, x = 0, 0.3, 0.7, 1.1) for the hydrogenation of cinnamaldehyde. The catalysts were characterized using Transmission Electron Microscopy (TEM), X-ray Diffraction (XRD), Raman spectroscopy, and X-ray Photoelectron Spectroscopy (XPS). The introduction of Fe was found to increase the average particle size of the bimetallic catalysts compared to the monometallic Ni@C. Ni existed in both metallic and oxide states, while Fe exhibited multiple oxidation states in the bimetallic catalysts. The carbon layer, approximately 2–3 nm thick, was confirmed to envelop the alloy particles. The catalytic performance of carbon−coated Ni−Fe alloy catalysts indicated that the addition of Fe to Ni@C enhanced the selectivity towards hydrocinnamaldehyde (HCAL), with NiFe0.7@C showing the highest selectivity (~88.6%) but at a reduced conversion rate. The carbon layer played a pivotal role in the stability and reusability of the catalysts. NiFe0.7@C maintained consistent performance over multiple reaction cycles, while NiFe0.7 NPs (without a carbon layer) exhibited significant deactivation. Both catalysts displayed strong magnetism, facilitating easy separation from the reaction mixture. This study sheds light on the significance of the carbon layer in bimetallic catalysts and provides valuable insights for designing efficient catalysts for hydrogenation processes. [ABSTRACT FROM AUTHOR]