Polyelectrolyte Nanoparticles Research Articles

Single Particle Insights into the Thermal Sensing of Conjugated Polyelectrolyte–Nanoparticle Assemblies

Single Particle Insights into the Thermal Sensing of Conjugated Polyelectrolyte–Nanoparticle Assemblies

Platelet-cloaked alginate-poly (β-amino ester) a novel platform bioinspired polyelectrolyte nanoparticle for targeted delivery of carboplatin in breast cancer: An in vitro/in vivo study

Triple-negative breast cancer (TNBC) has poor prognosis. Carboplatin (Crb) is a widely used chemotherapeutic agent, in TNBC but with serious systemic toxicity and poor tumor targeting. Bioinspired drug-loaded platelets (Plt) and Plt-coated nanocarriers evade macrophage phagocytosis by membrane proteins like CD47. The goal of this study was preparation of a novel alginate-poly (β-amino ester) (PβAE) nanoparticles (NPs) for targeted delivery of Crb to TNBC cells by developing and comparison of two bioinspired carriers of Plt membrane (PltM) coated Crb-loaded alginate-poly (β-amino ester) nanoparticles (PltM@Crb-PβAE-ALG NPs) and Plt loaded Crb (Plt@Crb). The NPs were prepared by ionic gelation and subsequently were coated by platelet membrane using ultra-sonication method. The loading efficiency, release profile, and in vitro cytotoxicity of both formulations were evaluated on HUVEC and 4 T1 cells. Additionally, the in vivo tumor targeting, therapeutic efficacy, and organ toxicity of the two formulations were assessed in a murine tumor model. Results showed both Plt@Crb and (PltM@Crb-PβAE-ALG NPs) exhibited high drug loading efficiency, sustained release, enhanced cytotoxicity against 4 T1 cells, and decreased cytotoxicity in normal cells (HUVEC) in vitro. In vivo studies revealed that although both formulations considerably improved tumor inhibition compared to free Crb, but the PltM@Crb-PβAE-ALG NPs demonstrated superior cytotoxicity and therapeutic efficacy, thanks to improved Crb’s internalization efficiency, enhanced stability, and controlled release properties.

Evaluation of polyelectrolyte nanoparticles of chitosan and hyaluronic acid as topical delivery systems for cytotoxic agents

In this study, we developed polyelectrolyte complexes (PECs), composed of hyaluronic acid and chitosan, aiming at obtaining a bioadhesive topical formulation for potential application for skin cancer treatment. Selected nanocarriers were obtained at a 1:1 (w/w) ratio of polyelectrolytes (0.25 mg/mL each) and probe sonication, displayed nanometric size (209.4 nm, PDI = 0.19), and cationic zeta potential (+28.0 mV). PECs presented bioadhesive potential, demonstrated by shifts in size and zeta potential upon incubation with mucin, and reduced transepidermal water loss. Paclitaxel (PTX) and 5-fluorouracil (5-FU), cytotoxic drugs with distinct physical-chemical characteristics, were incorporated at 0.25 and 0.75 %, respectively; propylene glycol addition was necessary for PTX incorporation. Compared to the control, 2.3- (9.4±3.6 μg/cm2) and 4.5-fold (2.8±0.8 μg/cm2) increases in PTX penetration into the stratum corneum and viable skin layers, respectively, were observed after 12 hours. No increase in 5-FU penetration was demonstrated. Incorporation in PECs resulted in slight increases in the cytotoxicity of PTX and 5-FU against melanoma cells, reducing IC50 values by 1.5- and 1.2-fold (1.55 and 35.10 μM for PTX and 5-FU, respectively) compared to the control solutions. IC50 values found for keratinocytes were higher (5.74 and 162.6 μM for paclitaxel and 5-FU, respectively). At non-cytotoxic concentrations, drug-loaded PECs promoted 24–31 % reductions on cell migration, suggesting that drug incorporation in PECs did not hinder their biological effects.

Rational Design of Pectin-Chitosan Polyelectrolyte Nanoparticles for Enhanced Temozolomide Delivery in Brain Tumor Therapy.

Conventional chemotherapeutic approaches currently used for brain tumor treatment have low efficiency in targeted drug delivery and often have non-target toxicity. Development of stable and effective drug delivery vehicles for the most incurable diseases is one of the urgent biomedical challenges. We have developed polymer nanoparticles (NPs) with improved temozolomide (TMZ) delivery for promising brain tumor therapy, performing a rational design of polyelectrolyte complexes of oppositely charged polysaccharides of cationic chitosan and anionic pectin. The NPs' diameter (30 to 330 nm) and zeta-potential (-29 to 73 mV) varied according to the initial mass ratios of the biopolymers. The evaluation of nanomechanical parameters of native NPs demonstrated changes in Young's modulus from 58 to 234 kPa and adhesion from -0.3 to -3.57 pN. Possible mechanisms of NPs' formation preliminary based on ionic interactions between ionogenic functional groups were proposed by IR spectroscopy and dynamic rheology. The study of the parameters and kinetics of TMZ sorption made it possible to identify compounds that most effectively immobilize and release the active substance in model liquids that simulate the internal environment of the body. A polyelectrolyte carrier based on an equal ratio of pectin-chitosan (0.1% by weight) was selected as the most effective for the delivery of TMZ among a series of obtained NPs, which indicates a promising approach to the treatment of brain tumors.

Preparation, stability, and antibacterial activity of carboxymethylated Anemarrhena asphodeloides polysaccharide-chitosan nanoparticles loaded curcumin

In present study, polysaccharide polyelectrolyte nanoparticles (CMAAP-CS NPs) were constructed by mixing carboxymethylated Anemarrhena asphodeloides polysaccharide (CMAAP) and chitosan (CS). CMAAP-CS NPs were applied as carrier to improve the bioavailability and stability of curcumin (Cur). The average particle size of CMAAP-CS NPs was 216.60 ± 4.21 nm and the entrapment efficiency of Cur reached 82.50 ± 2.09 %. The simulated digestion experiments in vitro confirmed that the bioavailability of Cur loaded in CMAAP-CS NPs was 59.84 ± 0.03 % after saliva, gastric and intestinal digestion, which was obvious higher than 21.57 ± 0.07 % of free Cur under the same conditions. The results of stability testing revealed that CMAAP-CS NPs could markedly reduce the degradation of Cur against storage, heating, UV light treatment, and neutral pH. This study provided promising polyelectrolyte complex loaded hydrophobic nutrients in medicine industry.

Cationized gelatin-sodium alginate polyelectrolyte nanoparticles encapsulating moxifloxacin as an eye drop to treat bacterial keratitis

A mucoadhesive polyelectrolyte complex (PEC) nanoparticles were developed for ocular moxifloxacin (Mox) delivery in Bacterial Keratitis (BK). Moxifloxacin-loaded G/CG-Alg NPs were prepared by an amalgamation of cationic polymers (gelatin (G)/cationized gelatin (CG)), and anionic polymer (sodium alginate (Alg)) along with Mox respectively. Mox@CG-Alg NPs were characterized for physicochemical parameters such as particle size (DLS technique), morphology (SEM analysis), DSC, XRD, encapsulation efficiency, drug loading, mucoadhesive study (by texture analyzer), mucin turbidity, and viscosity assessment. The NPs uptake and toxicity of the formulation were analyzed in the Human Corneal Epithelial (HCE) cell line and an ocular irritation study was performed on the HET-CAM. The results indicated that the CG-Alg NPs, with optimal size (217.2 ± 4 nm) and polydispersity (0.22 ± 0.05), have shown high cellular uptake in monolayer and spheroids of HCE. The drug-loaded formulation displayed mucoadhesiveness, trans-corneal permeation, and sustained the release of the Mox. The anti-bacterial efficacy studied on planktonic bacteria/biofilms of P. aeruginosa and S. aureus (in vitro) indicated that the Mox@CG-Alg NPs displayed low MIC, higher zone of bacterial growth inhibition, and cell death compared to free Mox. A significant reduction of bacterial load was observed in the BK-induced mouse model.

Encapsulation with Chitosan-Alginate polyelectrolyte nanoparticles increases the anti-cancer activity and bioactive compounds of Spirulina platensis algae.

Encapsulation with Chitosan-Alginate polyelectrolyte nanoparticles increases the anti-cancer activity and bioactive compounds of Spirulina platensis algae.

Absorption of oenothein B nanoparticles constructed using casein phosphopeptide and chitosan

The Oenothein B (OEB) rich in eucalyptus is a kind of extremely development of prospects of antioxidant activity, but low oral bioavailability limits its application. The novel polyelectrolyte nanoparticle was designed for OEB delivery through the self-assembly of casein phosphopeptides (CPP) and natural active polysaccharides-chitosan (CS). The OEB nanoparticle with small particle size and high embedding rate were constructed to solve the problem of low oral bioavailability of OEB, and its stability as well as in vivo absorption were investigated. The storage stability analysis, digital inverted fluorescence microscopy and emission field scanning electron microscopy showed that the particle size and total amount of OEB nanoparticles did not vary significantly after 96 h of continuous storage at room temperature, and the particle size distribution was uniform, and the particles kept their integrity pH 1.2. The maximum release rate of OEB nanoparticles was only 0.72% in artificial gastric fluid and 21.77% in artificial intestinal fluid. It greatly reduces the risk of its decomposition and plays a better protective role. The results of in vivo absorption showed that OEB nanoparticle gavage mice did not detect OEB in blood and its metabolites except for OEB in gastric juice, indicating that OEB changes in vivo after release. Therefore, although OEB nanoparticles can effectively protect their decomposition in gastrointestinal fluid, it is best to achieve sustained release at the target location in order to improve the absorption and utilization effect.

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

In this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4.

Rational polyelectrolyte nanoparticles endow preosteoclast-targeted siRNA transfection for anabolic therapy of osteoporosis

Targeted transfection of siRNA to preosteoclasts features the potential of anti-osteoporosis, yet challenge arises from the development of satisfied delivery vehicles. Here, we design a rational core-shell nanoparticle (NP) composed of cationic and responsive core for controlled load and release of small interfering RNA (siRNA) and compatible polyethylene glycol shell modified with alendronate for enhanced circulation and bone-targeted delivery of siRNA. The designed NPs perform well on transfection of an active siRNA (siDcstamp) that interferes Dcstamp mRNA expression, leading to impeded preosteoclast fusion and bone resorption, as well as promoted osteogenesis. In vivo results corroborate the abundant siDcstamp accumulation on bone surfaces and the enhanced trabecular bone mass volume and microstructure in treating osteoporotic OVX mice by rebalancing bone resorption, formation, and vascularization. Our study validates the hypothesis that satisfied transfection of siRNA enables preserved preosteoclasts that regulate bone resorption and formation simultaneously as potential anabolic treatment for osteoporosis.

Polyelectrolyte nanoparticles based on poly[N-(2-hydroxypropyl)methacrylamide-block-poly(N-(3-aminopropyl)methacrylamide] copolymers for delivery of heparin-binding proteins

In addition to the delivery of therapeutic nucleic acids and low-molecular weight drugs, polyelectrolyte nanoparticles (NPs) have recently been studied as carriers for protein delivery. However, the stability of NPs during isolation steps, which ensures their easy redispersion, needs to be solved empirically for individual systems using cryoprotectants and stabilizers. To avoid the use of additives, we studied the formation of polyelectrolyte NPs consisting of a newly synthesized polycationic diblock copolymer based on poly(N-(2-hydroxypropyl)methacrylamide)-block-poly(N-(3-aminopropyl)methacrylamide) (p(HPMA-b-APMA) and heparin (Hep). The p(APMA) blocks electrostatically complexed with Hep, and the p(HPMA) blocks formed a neutral corona of NPs, limiting NP aggregation. Self-assembly was monitored through the changes in size and zeta potential of the formed NPs, which depended on the copolymer composition and the concentration of polyelectrolyte solutions. The interactions between the NP components were analysed by FTIR spectroscopy, and XPS analysis indicated the presence of p(HPMA) blocks on the surface of the NPs. The encapsulation of the model chemokine CXCL12 and basic fibroblast growth factor (FGF-2) was driven by their specific bioaffinity for Hep, resulting in a high 90 % entrapment efficiency and increased protein stability. CXCL12 was released over 48 h, while FGF-2 exhibited a sustained release of up to 38 % over four weeks. In addition, the released CXCL12 effectively stimulated the migration of macrophages and T-lymphocyte cells, indicating the preserved protein bioactivity. Considering the proven noncytotoxic performance of the NPs towards fibroblasts and mesenchymal stem cells, the polyelectrolyte NPs of p(HPMA-b-APMA) and Hep loaded with heparin-binding proteins can be considered as promising candidates for the controlled delivery of bioactive proteins in biomedical applications.

Whey Protein Isolate-Chitosan PolyElectrolyte Nanoparticles as a Drug Delivery System.

Whey protein isolate (WPI), employed as a carrier for a wide range of bioactive substances, suffers from a lack of colloidal stability in physiological conditions. Herein, we developed innovative stabilized PolyElectrolyte Nanoparticles (PENs) obtained by two techniques: polyelectrolyte complexation of negatively charged WPI and positively charged chitosan (CS), and ionic gelation in the presence of polyanion tripolyphosphate (TPP). Therefore, the WPI-based core was coated with a CS-based shell and then stabilized by TPP at pH 8. The nanostructures were characterized by physiochemical methods, and their encapsulation efficiency and in vitro release were evaluated. The spherical NPs with an average size of 248.57 ± 5.00 nm and surface charge of +10.80 ± 0.43 mV demonstrated high encapsulation efficiency (92.79 ± 0.69) and sustained release of a positively charged chemotherapeutic agent such as doxorubicin (DOX). Z-average size and size distribution also presented negligible increases in size and aggregates during the three weeks. The results obtained confirm the effectiveness of the simultaneous application of these methods to improve the colloidal stability of PEN.

Characterization of drug-loaded alginate-chitosan polyelectrolyte nanoparticles synthesized by microfluidics

Characterization of drug-loaded alginate-chitosan polyelectrolyte nanoparticles synthesized by microfluidics

Tannic Acid-Aminated Sugar Beet Pectin Nanoparticles as a Stabilizer of High-Internal-Phase Pickering Emulsions.

Pickering stabilizers with additional antioxidant, photostabilizing, and metal-chelating properties are suitable for structuring multifunctional Pickering emulsion systems. Tannic acid (TA) is a potential material which when adsorbed onto the interface may impart antioxidant, UV-light-shielding, and chelating properties to Pickering stabilizers. Herein, we report a type of TA polyelectrolyte nanoparticles (NPs) fabricated following a complexation between TA and aminated sugar beet pectin (SBP-NH2). This study is geared toward investigating the performance of TA/SBP-NH2 NPs in stabilizing Pickering emulsions and protecting β-carotene from degradation. TA/SBP-NH2 NPs formed under optimum conditions had a mean diameter of 82 nm with a sphere-like shape. Because of their favorable surface wettability (91.2°), TA/SBP-NH2 NPs promoted formation of the low-, medium-, and high-internal-phase Pickering emulsions (HIPEs) in an oil volume fraction (φ)-dependent manner; the TA/SBP-NH2 NP-stabilized HIPE demonstrated viscoelastic properties increasing with the increasing concentration (c) of nanoparticles. Due to the excellent storage stability and UV light-absorbing capacity, the photostability of β-carotene was significantly improved by a TA/SBP-NH2 NP-stabilized HIPE (φ = 0.75; c = 3 mg/mL). Altogether, this study highlights that TA/SBP-NH2 NPs have potential applications in structuring Pickering emulsions with improved protective effects on loaded lipophilic compounds.

Polysaccharide-based nanoparticles fabricated from oppositely charged curdlan derivatives for curcumin encapsulation

In this study, carboxylic curdlan (Cur-48) and negatively charged ferulic acid (FA)-grafted carboxylic curdlan (Cur-48-g-FA) were separately used to fabricate polyelectrolyte nanoparticles (PNPs: PNPs-CQ and PNPs-CFQ) with positively charged quaternized curdlan (Qcurd) for curcumin delivery. Results showed that curcumin-loaded PNPs-CQ and PNPs-CFQ had particle sizes of 338.1 and 301.3 nm, zeta potentials of −19.07 and −24.10 mV, and encapsulation efficiencies of 76.32% and 83.54%, respectively. Curcumin was properly encapsulated inside the two PNPs through electrostatic interactions and hydrogen bonds. Compared with free curcumin, entrapped curcumin in the two PNPs exhibited better redispersion performance, thermo- and photostability, and sustained release property. Furthermore, FA molecules surrounding the surface of PNPs-CFQ were conductive to the entrapped curcumin's particulate characteristics, stability, release behavior, and antioxidant potentials. Therefore, our findings indicated that PNPs formulated via Cur-48-g-FA and Qcurd can provide a novel delivery platform for encapsulation of hydrophobic nutrients, including curcumin, in functional foods.

Benchmarking the Solubility Enhancement and Storage Stability of Amorphous Drug-Polyelectrolyte Nanoplex against Co-Amorphous Formulation of the Same Drug.

Amorphization, typically in the form of amorphous solid dispersion (ASD), represents a well-established solubility enhancement strategy for poorly soluble drugs. Recently, two amorphous drug formulations, i.e., the amorphous drug–polyelectrolyte nanoparticle complex (nanoplex) and co-amorphous system, have emerged as promising alternatives to circumvent the issues faced by ASD (i.e., large dosage requirement, high hygroscopicity). In the present work, the nanoplex was benchmarked against the co-amorphous system in terms of the preparation efficiency, drug payload, thermal stability, dissolution rate, supersaturation generation, and accelerated storage stability. Weakly acidic curcumin (CUR) and weakly basic ciprofloxacin (CIP) were used as the model poorly soluble drugs. The CUR and CIP nanoplexes were prepared using chitosan and sodium dextran sulfate as the polyelectrolytes, respectively. The co-amorphous CUR and CIP were prepared using tannic acid and tryptophan as the co-formers, respectively. The benchmarking results showed that the amorphous drug nanoplex performed as well as, if not better than, the co-amorphous system depending on the drug in question and the aspects being compared. The present work successfully established the nanoplex as an equally viable amorphous drug formulation as the more widely studied co-amorphous system to potentially serve as an alternative to ASD.

Structure of nanoparticle‐polyelectrolyte complexes: Effects of polyelectrolyte characteristics and charge ratio

AbstractWe present structural and turbidimetric characterizations of aqueous dispersions of oppositely charged nanoparticles and polyelectrolytes that undergo complexation and flocculation to form particle‐rich agglomerates over a wide range of polyelectrolyte and nanoparticle concentrations with varying polyelectrolyte sizes and persistence lengths. Compaction of nanoparticles in the polyelectrolyte–nanoparticle complexes, signified by decreasing internanoparticle spacing until they are brought in near‐contact, is observed upon increasing screening of interparticle repulsion arising from adsorption of polyelectrolytes on the nanoparticle surfaces. We identify the ratio of charge borne by the polyelectrolytes and the nanoparticles as a key parameter dictating the compaction of nanoparticles into complexes as well as densification of complexes into agglomerates. Moreover, the emergence of turbidity in solution is shown to correlate with the initiation of nanoparticle compaction by polyelectrolytes but failing to describe further structural evolution of the complexes, emphasizing the need for alternate characterization techniques.

Nanoparticle-Based Rifampicin Delivery System Development

The alkaline milieu of chronic wounds severely impairs the therapeutic effect of antibiotics, such as rifampicin; as such, the development of new drugs, or the smart delivery of existing drugs, is required. Herein, two innovative polyelectrolyte nanoparticles (PENs), composed of an amphiphilic chitosan core and a polycationic shell, were synthesized at alkaline pH, and in vitro performances were assessed by 1H NMR, elemental analysis, FT-IR, XRD, DSC, DLS, SEM, TEM, UV/Vis spectrophotometry, and HPLC. According to the results, the nanostructures exhibited different morphologies but similar physicochemical properties and release profiles. It was also hypothesized that the simultaneous use of the nanosystem and an antioxidant could be therapeutically beneficial. Therefore, the simultaneous effects of ascorbic acid and PENs were evaluated on the release profile and degradation of rifampicin, in which the results confirmed their synergistic protective effect at pH 8.5, as opposed to pH 7.4. Overall, this study highlighted the benefits of nanoparticulate development in the presence of antioxidants, at alkaline pH, as an efficient approach for decreasing rifampicin degradation.

Selective separation of polyelectrolyte nanoparticles based on formation of hydrogen-bonding interpolymer complexes

Nano-spherical polyelectrolyte brushes (SPBs) have been demonstrated to be versatile objects for many high-tech applications due to their unique microenvironment and impressive stability in aqueous media, showing great prospects in industry. However, the recycling of valuable SPBs is still a big obstacle, thereby limiting their industrial applications. Here, we show a facile approach to efficiently separate SPBs from aqueous latex solution on the basis of spherical poly(acrylic acid) brushes with a polystyrene core (PS-PAA brushes). Upon addition of poly(ethylene oxide) (PEO), hydrogen-bonding interpolymer complexes consisting of PS-PAA brushes and PEO are formed at pH below 3.5, leading to selective separation of the PS-PAA brushes from aqueous media containing other nanoparticles. Near all of the brushes are separated at pH below 3.0 regardless of the ion strengths. Importantly, the brushes can be easily redispersed by simply increasing pH, showing ignorable variations of the intrinsic properties like diameter, surface charge and light transmittance. As an application example, a catalytic nanoreactor is developed by loading sliver nanoparticles (Ag NPs) in PS-PAA brushes which show neglectable deteriorations of catalysis on the model reaction even after four separation–redispersion cycles. This work provides a simple way for selective separation of SPBs, which may benefit for industrial applications of SPBs.

One‐step production of polyelectrolyte nanoparticles

AbstractNeutral polymeric nanoparticles have found many important applications in fields such as drug delivery, biosensing and environmental research. However, charged polymeric nanoparticles have not yet found such success mainly due to the multi‐step and time‐consuming conventional production route. An emulsification–evaporation method was described as a fast and reproducible way to obtain neutral polymeric nanosuspensions. We propose here, for the first time, to extend this method to the one‐step production of negatively charged polymeric nanoparticles. For this purpose, we compared different processes, namely sonication, shear mixing and elongational‐flow micromixing (μRMX), in order to produce polyelectrolyte nanoparticles (PNPs) of poly(styrene sulfonate). We found that only μRMX allowed the production of highly monodispersed PNPs. We also verified the decrease of nanoparticle size (from 300 to 150 nm) and polydispersity index by increasing the emulsification time and decreasing the polymer molecular weight. Finally, we observed and explained the causes of an unusual behavior: the sudden increase of PNP size after a given emulsification time when using μRMX. © 2021 Society of Chemical Industry