Polyelectrolyte Complex Nanoparticles Research Articles

Performance of delaying release and reducing adsorption of polyethyleneimine/poly(vinyl sulfonate) polyelectrolyte complex nanoparticles in polyacrylamide/polyethyleneimine gel system

Polyacrylamide/Polyethyleneimine (HPAM/PEI) is an environmentally friendly and promising gel system. However, inadequate gelation time and retention of the cross-linker (polyethyleneimine, PEI) during migration pose significant challenges for effective water control treatment in deep reservoirs. Polyelectrolyte complex nanoparticles (PECs) have demonstrated the ability to efficiently encapsulate PEI, facilitating for its gradual release. To achieve this, a cost-effective polyanionic complex, poly(vinyl sulfonate) (PVS), was employed to form PECs with PEI. By adjusting the mixing ratio of PEI and PVS, stable PECs suspensions with varying charges were successfully produced. These stable PECs exhibited spherical shapes with a particle size distribution ranging from 127.3–442.71 nm, and an average particle size of approximately 200 nm. The encapsulation efficiency of PEI by PECs varied from 64.56 % to 86.14 %. Under different conditions, 55.12 % to 90.26 % of PEI could be released from PECs. Increased temperatures, higher ionic strengths, and greater deviations in pH from the initial state of the PECs suspension all facilitated the release of PEI. The most stable PECs delayed the gelation time of the HPAM/PEI system to 9.5 days, which is twice the base gelation time of 4.5 days. The strength of mature HPAM/PEI (PECs) gels increased by 8.95 Pa in storage modulus (G′) compared to HPAM/PEI at the same concentration, albeit with a reduced linear viscoelastic region. And, the PECs-based delayed crosslinking method does not negatively affect the mechanical strength of the HPAM/PEI gel system, and thus its water control ability, under reservoir conditions. On the other hand, the static adsorption of PEI encapsulated by anionic PECs on sand decreased to one-fourth of that of free PEI (PEI solution). Additionally, the breakthrough of PEI encapsulated in anionic PECs in fractured sandstone cores was significantly advanced compared to free PEI.

Development of chitosan/sodium carboxymethyl cellulose-based polyelectrolyte complex of dexamethasone for treatment of anterior uveitis

Anterior uveitis is one of the most prevalent forms of ocular inflammation caused by infections, trauma, and other idiopathic conditions if not treated properly, it can cause complete blindness. Therefore, this study aimed to formulate and evaluate dexamethasone sodium phosphate (DSP) loaded polyelectrolyte complex (PEC) nanoparticles (NPs) for the treatment of anterior uveitis. DSP-loaded PEC-NPs were formed through complex coacervation by mixing low molecular weight chitosan and the anionic polymer carboxy methyl cellulose (CMC). The formulations were optimized using Box-Behnken design and evaluated the effect of independent variables: Chitosan concentration, CMC concentration, and pH of chitosan solution on the dependent variables: particle size (PS), Polydispersity Index (PDI), pH of the formulation, and % entrapment efficacy (%EE). The PS, PDI, zeta potential, and pH of the optimized formulation were found 451 ± 82.0995 nm, 0.3807 ± 0.1862, +20.33 ± 1.04 mV and 6.8367 ± 0.0737 respectively. The %EE and drug loading of formulation were 61.66 ± 4.2914% and 21.442 ± 1.814% respectively.In vitrodrug release studies of optimized formulation showed the prolonged release up to 12 h whereas, the marketed formulation showed the burst release 85.625 ± 4.3062% in 1 h and 98.1462 ± 3.0921% at 6 h, respectively. Fourier transform infrared studies suggested the effective incorporation of the drug into the PEC-NPs formulation whereas differential scanning calorimetry and x-ray diffraction studies showed the amorphized nature of the drug in the formulation. Transmission electron microscopy study showed self-assembled, nearly spherical, core-shell nanostructures. The corneal permeation study showed higher permeation of the drug from PEC-NPs compared to the marketed formulation. Hen's Eggs test-Chorioallantoic Membrane test of the optimized formulation revealed non-irritant and safe for ocular administration. Therefore, DSP-loaded PEC-NPs are an effective substitute for conventional eye drops due to their ability to increase bioavailability through longer precorneal retention duration and sustained drug release.

Immunomodulatory hydrogel orchestrates pro-regenerative response of macrophages and angiogenesis for chronic wound healing

Chronic wound healing often encounters challenges characterized by prolonged inflammation and impaired angiogenesis. While the immune response plays a pivotal role in orchestrating the intricate process of wound healing, excessive inflammation can hinder tissue repair. In this study, a bilayer alginate hydrogel system encapsulating polyelectrolyte complex nanoparticles (PCNs) loaded with anti-inflammatory cytokines and angiogenic growth factors is developed to address the challenges of chronic wound healing. The alginate hydrogel is designed using two distinct crosslinking methods to achieve differential degradation, thereby enabling precise spatial and temporal controlled release of PCNs. Initially, interleukin-10 (IL-10) is released to mitigate inflammation, while unsaturated PCNs bind and remove accumulated pro-inflammatory cytokines at the wound site. Subsequently, angiogenic growth factors, including vascular endothelial growth factor and platelet-derived growth factor, are released to promote vascularization and vessel maturation. Our results demonstrate that the bilayer hydrogel exhibits distinct degradation kinetics between the two layers, facilitating the staged release of multiple signaling molecules. In vitro experiments reveal that IL-10 can activate the Jak1/STAT3 pathway, thereby suppressing pro-inflammatory cytokines and chemokines while down-regulating inflammation-related genes. In vivo studies demonstrate that application of the hydrogel in chronic wounds using diabetic murine model promotes healing by positively modulating multiple integral reparative mechanisms. These include reducing inflammation, promoting macrophage polarization towards a pro-regenerative phenotype, enhancing keratinocyte migration, stimulating angiogenesis, and expediting wound closure. In conclusion, our hydrogel system effectively mitigates inflammatory responses and provides essential physiological cues by inducing a synergistic angiogenic effect, thus offering a promising approach for the treatment of chronic wounds.

Design, optimization and characterization of atorvastatin loaded chitosan-based polyelectrolyte complex nanoparticles based transdermal patch

AimAtorvastatin (ATO) loaded chitosan-based polyelectrolyte complex nanoparticles (PECN) incorporated transdermal patch was developed to enhance its skin permeability and bioavailability. MethodologyThe ATO loaded PECN were prepared by ionic gelation method and optimized by Box-Behnken design. The optimized batches were evaluated for physicochemical characteristics, in vitro, ex vivo, cell line and stability studies. The optimized ATO-PECN were incorporated into transdermal patches by solvent evaporation method and evaluated for their physicochemical properties, ex vivo skin permeation, in vivo pharmacokinetics and stability study. ResultsThe optimized batch of ATO-PECN had average size of 219.2 ± 5.98 nm with 82.68 ± 2.63 % entrapment and 25.41 ± 3.29 mV zeta potential. ATO-PECN showed sustained drug release and higher skin permeation. The cell line study showed that ATO-PECN increased the cell permeability of ATO as compared to ATO suspension. ATO-PECN loaded transdermal patch showed higher skin permeation. The in vivo pharmacokinetic study revealed that the ATO-PECN transdermal patch showed significant (p < 0.05) increase in pharmacokinetic parameters as compared to marketed oral tablet, confirming enhancement in bioavailability of ATO. ConclusionsThe results of the present work concluded that the ATO-PECN loaded transdermal patch is a promising novel drug delivery system for poorly bioavailable drugs.

Abstract 3205: MicroRNA-peptide polyelectrolyte complex nanoparticle-hydrogel composite attenuates mesothelioma growth

Abstract Diffuse pleural mesothelioma (DPM) is a biologically unusual, aggressive asbestos-associated cancer affecting the entire pleura surface. DPM defies current standard multimodal therapies due to intrinsic chemoresistance and inability to achieve negative-margin resection of complex surface anatomy. Hence, current non-specific drug regimens ultimately fail because the biology of this tumor is poorly understood and even if surgically resected, tumor inevitably recurs from residual microscopic tumor foci. These various clinical challenges led us to develop a therapeutic platform delivering microRNA (miRNA), a novel anti-cancer agent therapeutic regimen, with the goal of eradicating residual microscopic tumor foci thereby improving the efficacy of multimodal therapy. We engineered a peptide-based biodegradable hydrogel that can be injected or sprayed directly to coat anatomic surfaces (surface-fill hydrogel; SFH), functioning as a therapeutic depot. Properties of SFH allow us to specify critical composition parameters such as biopersistence time, therapeutic payload, cell-specific targeting etc. In the first step of SFH formulation, miRNA complexed with different amphiphilic cationic peptides varying in length (19-26 amino acids) and amines (9-17), to form stable nanoparticles. Flash nanocomplexation (FNC) were used to produce highly scalable and kinetically controlled assembly of miRNA-peptide polyelectrolyte complex (PEC) nanoparticles (NPs), which utilizes a confined impinging jet (CIJ) mixer to achieve turbulent micromixing of the NPs components, yielding highly uniform and stable NPs. Next, NPs were encapsulated into another peptide hydrogel, formed via self-assembly of amphiphilic cationic peptide HLT2, thus forming a surface-fill hydrogel NPs composite. The SFH-NPs composite was not toxic to DPM cells and demonstrated efficient release of miRNA-peptide NPs from the SFH matrix in-vitro. The uptake of FAM-labeled miRNA-peptide NPs was confirmed by flowcytometry. Biodistribution analysis of NPs in mice bearing luciferase-positive DPM xenografts treated locally with Cy3-miRNA-SFH composite showed that Cy3-miRNA was concentrated in tumor cells but not in other organs. Furthermore, miR-215 exhibiting potent anti-tumor activity in DPM was used to study the therapeutic efficacy of SFH miRNA-nanoparticle composites. Subcutaneous DPM xenografts treated locally with miR-215 SFH composite shrank tumor significantly. Thus, delivery of specific miRNA-peptide PEC nanoparticles via SFH therapeutic platform in preclinical models of DPM displayed potent anti-cancer effects. Together, this new generation microRNA-peptide polyelectrolyte complex nanoparticles-SFH composite is a very promising delivery platform that could be extended for a diverse array of locoregional therapies. Citation Format: Anand Singh, Anderson Caleb, Joel P. Schneider, Chuong D. Hoang. MicroRNA-peptide polyelectrolyte complex nanoparticle-hydrogel composite attenuates mesothelioma growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3205.

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.

Vitexin-loaded poly(ethylene glycol) methyl ether-grafted chitosan/alginate nanoparticles: Preparation, physicochemical properties, and in vitro release behaviors.

Vitexin, a flavonoid in various foods and medicinal plants, has potential clinical, therapeutic, and food applications due to its bioactive properties and beneficial health effects. However, its poor water solubility causes low oral bioavailability and poor absorption in the gastrointestinal tract, limiting its practical applications. Encapsulation is an efficient approach to overcome these limitations. This study demonstrates the encapsulation of vitexin into poly(ethylene glycol) methyl ether-grafted chitosan (mPEG-g-CTS)/alginate (ALG) polyelectrolyte complex nanoparticles. The vitexin-loaded mPEG-g-CTS/ALG nanoparticles were characterized by Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, and X-ray diffraction. The vitexin-loaded mPEG-g-CTS/ALG nanoparticles had a spherical shape, 50-200 nm diameter, and negatively charged surface (-27 to -38 mV). They possessed a loading capacity of 4%-60%, encapsulation efficiency of 50%-100%, and antioxidant activity (30%-52% 2,2-diphenyl-1-picrylhydrazyl decoloration) when their initial vitexin content was 0.02-0.64 g/g polymers. Successful vitexin loading into mPEG-g-CTS/ALG nanoparticles was also indirectly confirmed by the enhanced thermal stability of both polymers and the residual soybean oil used in the emulsion preparation step and delayed oxidative degradation of the residual soybean oil. Vitexin's in vitro release from the mPEG-g-CTS/ALG nanoparticles was very fast in phosphate buffer at pH 11, followed by pH 7, and very slow in acetate buffer at pH 3. The gastrointestinal digestion of vitexin increased by encapsulating into mPEG-g-CTS/ALG nanoparticles. The vitexin-loaded mPEG-g-CTS/ALG nanoparticles were successfully fabricated using a two-step process of oil-in-water emulsion and ionic gelation without pungent odor acids and other crosslinkers. The obtained nanoparticles are suitable for oral intestinal-specific delivery systems. This article is protected by copyright. All rights reserved.

Targeting the Mannose Receptor with Functionalized Fucoidan/Chitosan Nanoparticles Triggers the Classical Activation of Macrophages.

Understanding how nanoparticles' properties influence their cellular interactions is a bottleneck for improving the design of carriers. Macrophage polarization governs their active role in solving infections or tissue repair. To unravel the effect of carbohydrate-targeting mannose receptors on the macrophage surface, drug-free fucoidan/chitosan nanoparticles were functionalized using mannose (M) and mannan (Mn). Polyelectrolyte complex nanoparticles were obtained upon chitosan self-assembly using fucoidan. The functionalized nanoparticles were characterized in terms of their physicochemical characteristics, chemical profile, and carbohydrate orientation. The nanoparticles varied in size from 200 to 400 nm, were monodisperse, and had a stable negative zeta potential with a low aggregation tendency. The nonfunctionalized and functionalized nanoparticles retained their properties for up to 12 weeks. Cell viability and internalization studies were performed for all the designed nanoparticles in the THP-1 monocytes and THP-1-differentiated macrophages. The expression of the mannose receptor was verified in both immune cells. The carbohydrate-functionalized nanoparticles led to their activation and the production of pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α. Both M- and Mn-coated nanoparticles modulate macrophages toward an M1-polarized state. These findings demonstrate the tailoring of these nanoplatforms to interact and alter the macrophage phenotype in vitro and represent their therapeutic potential either alone or in combination with a loaded drug for future studies.

Fabrication, characterization and evaluation of a new designed botulinum toxin-cell penetrating peptide nanoparticulate complex.

To have a better and longer effect, botulinum neurotoxin (BoNT) is injected several times in a treatment course, which could increase side effects and cost. Some of the most cutting-edge strategies being investigated for proteins to their physiologic targets involve the reformulation of BoNT based on peptide-based delivery systems. For this purpose, cell-penetrating peptides (CPPs) are of particular interest because of their capacity to cross the biological membranes. A short and simple CPP sequence was used as a carrier to create nanocomplex particles from BoNT/A, with the purpose of increasing toxin entrapment by target cells, reducing diffusion, and increasing the duration of the effect. CPP-BoNT/A nanocomplexes were formed by polyelectrolyte complex (PEC) method, considering the anionic structure of botulinum toxin and the cationic CPP sequence. The cellular toxicity, and absorption profile of the complex nanoparticles were evaluated, and the digit abduction score (DAS) was used to assess the local muscle weakening efficacy of BoNT/A and CPP-BoNT/A. The provided optimized polyelectrolyte complex nanoparticles had a 244 ± 20nm particle size and 0.28 ± 0.04 PdI. In cellular toxicity, CPP-BoNT/A nanocomplexes as extended-release formulations of BoNT/A showed that nanocomplexes had a more toxic effect than BoNT/A. Furthermore, the comparison of weakening effectiveness on muscle was done among nanoparticles and free toxin on mice based on the digit abduction score (DAS) method, and nanocomplexes had a slower onset effect and a longer duration of action than toxin. Using PEC method allowed us to form nanocomplex from proteins, and peptides without a covalent bond and harsh conditions. The muscle-weakening effect of toxin in CPP-BoNT/A nanocomplexes showed acceptable efficacy and extended-release pattern.

1504 Sequential release of immunomodulatory signaling molecules-laden polyelectrolyte complex nanoparticles from via bilayer alginate hydrogels promotes regenerative wound healing

1504 Sequential release of immunomodulatory signaling molecules-laden polyelectrolyte complex nanoparticles from via bilayer alginate hydrogels promotes regenerative wound healing

Evaluation of Polyelectrolyte Complex Nanoparticles for Prolonged Scale Inhibitor Release in Porous Media

The formation of inorganic scales on the surfaces of porous media, production wells, and pipelines can substantially reduce the efficiency of oil production and damage reservoir formations. Scale inhibitors (SIs) are often applied to prevent or mitigate scale formation using a “squeeze treatment”, where the SI is injected into a formation and allowed to equilibrate, and then the flow is reversed (return phase). Although organic polymers, such as poly(vinyl sulfonic acid) (PVS), can tolerate high temperatures and have been effective for scale control, repeated applications may be required because they exhibit weak adsorption (retention) in most reservoir formations. To address this limitation, the release performance of a polyelectrolyte complex nanoparticle (PECNP) loaded with PVS was evaluated in laboratory-scale squeeze tests and compared to PVS alone. After injection of the PECNP into a Berea sandstone core and a 24 h shut-in period, a brine solution was introduced to the core. Following injection, the free or “active” PVS concentration in the effluent spiked to approximately 600 mg/L, decreased to 10 mg/L after 10 pore volumes (PVs), and then gradually declined to concentrations between 1 and 3 mg/L over the remaining 450 PVs of the test. Minimal PECNPs were detected in effluent samples during the return phase, indicating that PECNP attachment was irreversible under these experimental conditions. In contrast, the PVS-only squeeze test exhibited elevated PVS concentrations that approached the applied concentration immediately after a brine solution was introduced during the return phase, and the PVS return concentration decreased to below the detection limit (0.5 mg/L) after only 70 PVs. A mathematical model that incorporated nanoparticle attachment and rate-limited release of the SI successfully reproduced the experimental results and can be used to predict PECNP squeeze lifetime. These findings demonstrate the potential application of PECNPs for scale control in reservoir formations.

Skin targeting by chitosan/hyaluronate hybrid nanoparticles for the management of irritant contact dermatitis: In vivo therapeutic efficiency in mouse-ear dermatitis model

Irritant contact dermatitis (ICD) is an inflammatory skin condition characterized by severe eczematous lesions. Nanoparticulate drug delivery is the most predominant way to improve dermal penetration and have gained remarkable recognition for targeted delivery of therapeutic payload and reduced off-target effects. Therefore, the current work aimed to fabricate polyelectrolyte complex nanoparticles (PENPs) containing two natural biodegradable polymers namely; chitosan (CS) and hyaluronic acid (HA) to deliver the non steroidal anti-inflammatory drug etoricoxib (ETX) to the deeper skin layers to alleviate any systemic toxicity and improve its therapeutic efficacy against ICD. ETX loaded-PENPs were prepared and optimized utilizing three independent variables; CS: HA mass ratio, chitosan solution pH and molecular weight of chitosan. Following the various physicochemical optimizations, the optimum ETX-loaded PENPs formulation (N1 0.15 %) exhibited spherical nature with an average diameter of 267.9 ± 9.4 nm, Polydispersity index of 0.366 ± 0.02, and positive zeta potential (+32.9 ± 0.47 mV). The drug was successfully entrapped and the entrapment efficiency reached 95 ± 0.2 %. N1 0.15 % formula showed efficient dermal targeting by significantly enhanced percentage of ETX permeated and retained in the various skin layers in comparison to ETX conventional gel during the ex-vivo skin permeation experiments. Furthermore, N1 0.15 % exhibited superior anti-inflammatory properties in vivo compared to ETX conventional gel in dithranol induced mice ear dermatitis. Conclusively, ETX-loaded PENPs could be a promising therapeutic approach for effecient management of ICD.

Design and in vitro/in vivo Evaluation of Polyelectrolyte Complex Nanoparticles Filled in Enteric-Coated Capsules for Oral Delivery of Insulin

Insulin is one of the most important drugs in the treatment of diabetes. There is an increasing interest in the oral administration of insulin as it mimics the physiological pathway and potentially reduces the side effects associated with subcutaneous injection. Therefore, insulin-loaded polyelectrolyte complex (PEC) nanoparticles were prepared by the ionic cross-linking method using protamine sulfate as the polycationic and sodium alginate as the anionic polymer. Taguchi experimental design was used for the optimization of nanoparticles by varying the concentration of sodium alginate, the mass ratio of sodium alginate to protamine, and the amount of insulin. The optimized nanoparticle formulation was used for further in vitro characterization. Then, insulin-loaded PEC nanoparticles were placed in hard gelatin capsules and the capsules were enteric-coated by Eudragit L100-55 (PEC-eCAPs). Hypoglycemic effects PEC-eCAPs were determined in vivo by oral administration to diabetic rats. Furthermore, in vivo distribution of PEC nanoparticles was evaluated by fluorescein isothiocyanate (FITC) labelled nanoparticles. The experimental design led to nanoparticles with a size of 194.4 nm and a polydispersity index (PDI) of 0.31. The encapsulation efficiency (EE) was calculated as 95.96%. In vivo studies showed that PEC-eCAPs significantly reduced the blood glucose level of rats at the 8th hour compared to oral insulin solution. It was concluded that PEC nanoparticles loaded into enteric-coated hard gelatin capsules provide a promising delivery system for the oral administration of insulin.

Sub-millimetric visualization and stability measurement for supercritical CO2 foams: Effect of ionic complexation on tubular and diverging flows

Development of natural gas resources as fuel for energy transition requires sustainable recovery processes with manageable amount of water used for unconventional stimulation of wellbores to protect the environment. To manage stability issues and bubble morphological alternations within the waterless fluids such as dry foams, microstructure and physiochemical properties were correlated to ionic complexation, bubble local plastic deformation (T1 event) in vicinity of constriction and elastoplastic behavior of CO2-water interface travelling from wellbore to fracture and flow back. This work presents facile sub-millimetric observation and step by step image analysis protocol for dry scCO2 foam transport and stability evaluation across the vertical view cell (tubular flow) and after constriction (diverging flow) and highlights the effect of viscoelastic components of interface on bubble plastic deformation and interfacial stability. The scCO2 foam’s microscopic structure was stabilized with (i) Zwitterionic Surfactants (ZS) and (ii) ZS-conjugated Polyelectrolyte Complex Nanoparticles (PECNP). PECNP-Surfactant scCO2 foam structure was noticeably affected by confinement ratio between the feeding tube and view cell, thus excessive lamella breakup and rearrangement of scCO2 bubbles occurred with higher rate in widening flow, which contributed to formation of less uniform dispersion of scCO2 droplets in PECNP-Surfactant scCO2 foam. However, the PECNP-Surfactant complexes residing in CO2-water lamella stabilized the deformed microstructure for significantly longer time. Bubble shape deformity was attributed to bubble elongation due to elastoplastic properties of lamella interface originated by the presence PECNP nanoparticle verified by higher dilatational elasticity at interface. Stability of deformed bubbles in pattern of PECNP-surfactant scCO2 foam with longer resistivity to lamella breakage, coalescence, and gravity drainage (up to 160 min) were compared to sudden bubble growth and expansion (after 30 min) detected for narrower distribution of smaller scCO2 bubbles stabilized in mixtures of ZS in high salinity brine (33.3 kppm). Higher resistance to morphological change (coalescence, rupture, burst) was observed for viscous lamella of PECNP-surfactant in scCO2 foam originated from higher viscosity and dilatational elasticity of lamella interface.

Application of mathematical modelling to alginate chitosan polyelectrolyte complexes for the prediction of system behavior with Venlafaxine HCl as a model charged drug

PurposeThis work aimed to develop and analyze the performance of chitosan/alginate polyelectrolyte complex (PEC). Multiple regression and Lab fit curve fitting were applied to derive empirical models for the prediction of zeta potential of plain systems as a function of alginate chitosan ratio. Venlafaxine-HCl was loaded as a model charged drug and empirical models for prediction of its release as a function of time were also derived. MethodsCoacervation method was used for the preparation of green PECs. Preliminary studies were conducted to optimize the preparation method. Pre-adjustment of the pH of alginate and chitosan sols enabled the formation of PECs at alginate/chitosan ratios starting from 1:9 to 9:1. On mixing of alginate and chitosan sols, equal volume dilution method produced spherical particles, while direct mixing method gave fibrous particles. Twenty-seven PECs nanoparticle formulae were prepared using nine alginate/chitosan ratios and three levels of total polymer concentrations. ResultsStatistical analysis showed that Zeta potential of the nanoparticle was significantly dependent on alginate/chitosan ratio, while particle size was a function of total polymer concentration. Nine fiber formulae were prepared and evaluated for their appearance and zeta potential. Venlafaxine-HCl release followed anomalous transport mechanism. FT-IR and DSC studies confirmed complexation at the carboxylate and amine site at alginate and chitosan respectively. ConclusionChitosan/alginate PECs were successfully obtained without a cross-linker and empirical equations were obtained to help finding the best composition for loading charged drugs and to predict their release profiles.

Chitosan IR806 dye-based polyelectrolyte complex nanoparticles with mitoxantrone combination for effective chemo-photothermal therapy of metastatic triple-negative breast cancer

Chemo-photothermal therapy is one of the emerging therapies for treating triple-negative breast cancer. In this study, we have used ionotropic gelation method to fabricate chitosan and IR806 dye-based polyelectrolyte complex (CIR-PEx) nanoparticles. These nano-complexes were in size range of 125 ± 20 nm. The complexation of IR 806 dye with chitosan improved photostability, photothermal transduction, and showed excellent biocompatibility. Cancer cells treated with CIR-PEx NPs enhanced intracellular uptake within 5 h of incubation and also displayed mitochondrial localization. With the combination of CIR-PEx NPs and a chemotherapeutic agent (i.e., mitoxantrone, MTX), a significant decline in cancer cell viability was observed in both 2D and 3D cell culture models. The chemo-photothermal effect of CIR-PEx NPs + MTX augmented apoptosis in cancer cells when irradiated with NIR light. Furthermore, when tested in the 4 T1-tumor model, the chemo-photothermal therapy showed a drastic decline in tumor volume and inhibited metastatic lung nodules. The localized hyperthermia caused by photothermal therapy reduced the primary tumor burden, and the chemotherapeutic activity of mitoxantrone further complemented by inhibiting the spread of cancer cells. The proposed chemo-photothermal therapy combination could be a promising strategy for treating triple-negative metastatic breast cancer.

Biocompatible Polyelectrolyte Complex Nanoparticles for Lycopene Encapsulation Attenuate Oxidative Stress-Induced Cell Damage.

In this study, lycopene was successfully encapsulated in polyelectrolyte complex nanoparticles (PEC NPs) fabricated with a negatively charged polysaccharide, TLH-3, and a positively charged sodium caseinate (SC) via electrostatic interactions. Results showed that the lycopene-loaded PEC NPs were spherical in shape, have a particle size of 241 nm, have a zeta potential of −23.6 mV, and have encapsulation efficiency of 93.6%. Thus, lycopene-loaded PEC NPs could serve as effective lycopene carriers which affected the physicochemical characteristics of the encapsulated lycopene and improved its water dispersibility, storage stability, antioxidant capacity, and sustained release ability in aqueous environments when compared with the free lycopene. Moreover, encapsulated lycopene could enhance the cells' viability, prevent cell apoptosis, and protect cells from oxidative damage through the Nrf2/HO-1/AKT signalling pathway, via upregulation of antioxidase activities and downregulation of MDA and ROS levels. Therefore, the biocompatible lycopene-loaded PEC NPs have considerable potential use for the encapsulation of hydrophobic nutraceuticals in the food and pharmaceutical industries.

Preparation of polyelectrolyte complex nanoparticles with tunable and narrow size distributions by template polymerization

Preparation of polyelectrolyte complex nanoparticles with tunable and narrow size distributions by template polymerization

Chitosan based polyelectrolyte complex nanoparticles: preparation and characterization

Chitosan based polyelectrolyte complex nanoparticles: preparation and characterization

Chitosan-based nanoparticles for controlled release of hydrophobic and hydrophilic drugs

Nanoparticles encapsulating different kinds of therapeutic drugs are promising drug delivery systems for controlling release and targeting tumor cells. Chitosan nanoparticles made by polyelectrolyte complexation were designed as drug carriers using doxorubicin (DOX)/5-fluorouracil (5-FU) as hydrophobic/hydrophilic model drugs. The sizes of nanoparticles were 235 ± 13 and 177 ± 7 nm with narrow distributions. The effects of the initial drug amount and pH of the medium on drug-controlled release properties were evaluated, the model-fitting results and release mechanisms were analyzed as well. For 5-FU-loaded chitosan nanoparticles, the controlled-release effect was superior to that of DOX, indicating that the polyelectrolyte complex nanoparticles were more suitable for hydrophilic drugs, particularly for negatively charged or electrically neutral drugs. Moreover, the release behaviors conformed with the first-order kinetic model, indicating that the nanoparticles were mainly released by diffusion during the drug release process; the system could also be fitted using the Higuchi model, showing that the entire drug release process was dominated by diffusion and supplemented by gradual dissolution. In all, the results suggested that chitosan nanoparticles made by polyelectrolyte complexation can be launched as a smart drug delivery system for cancer treatments.