Synergistic nanocoating with layer-by-layer functionalized PCL membranes enhanced by manuka honey and essential oils for advanced wound healing.

Chronic wounds represent a significant global health concern, statistically impacting 1-2% of the population in developed countries throughout their lifetimes. These wounds cause considerable discomfort for patients and necessitate substantial expenditures of time and resources for treatment. Among the emerging therapeutic approaches, medicated dressings incorporating bioactive molecules, including natural compounds, are particularly promising. Hence, the objective of this study was to develop novel antimicrobial dressings for wound treatment. Specifically, polycaprolactone membranes were manufactured using the electrospinning technique and subsequently coated with natural polyelectrolytes (chitosan as a polycation and a mixture of manuka honey with essential oils nanoemulsions as a polyanion) employing the Layer-by-Layer assembly technique. Physico-chemical and morphological characterization was conducted through QCM-D, FTIR-ATR, XPS, and SEM analyses. The results from SEM and QCM-D demonstrated successful layer deposition and coating formation. Furthermore, FTIR-ATR and XPS analyses distinguished among different coating compositions. The coated membranes were tested in the presence of fibroblast cells, demonstrating biocompatibility and expression of genes coding for VEGF, COL1, and TGF-ß1, which are associated with the healing process (assessed through RT-qPCR analysis). Finally, the membranes exhibited excellent antibacterial activity against both Staphylococcus aureus and Pseudomonas aeruginosa, with higher bacterial strain inhibition observed when cinnamon essential oil nanoemulsion was incorporated. Taken together, these results demonstrate the potential application of nanocoated membranes for biomedical applications, such as wound healing.

Enhancing cell activities through integration of polyanionic alginate or hyaluronic acid derivatives with triboelectric nanogenerators.

The impact of electrical stimulation has been widely investigated on the wound healing process; however, its practicality is still challenging. This study explores the effect of electrical stimulation on fibroblasts in a culture medium containing different electrically-charged polysaccharide derivatives including alginate, hyaluronate, and chitosan derivatives. For this aim, an electrical stimulation, provided by a zigzag triboelectric nanogenerator (TENG), was exerted on fibroblasts in the presence of polysaccharides' solutions. The analyses showed a significant increase in cell proliferation and an improvement in wound closure (160 % and 90 %, respectively) for the hyaluronate-containing medium by a potential of 3 V after 48 h. In the next step, a photo-crosslinkable hydrogel was prepared based on hyaluronic acid methacrylate (HAMA). Then, the cells were cultured on HAMA hydrogel and treated by an electrical stimulation. Surprisingly, the results showed a remarkable increase in cell growth (280 %) and migration (82 %) after 24 h. Attributed to the electroosmosis phenomenon and an amplified transfer of soluble growth factors, a dramatic promotion was underscored in cell activities. These findings highlight the role of electroosmosis in wound healing, where TENG-based electrical stimulation is combined with bioactive polysaccharide-based hydrogels to promote wound healing.

In situ formed aldehyde-modified hyaluronic acid hydrogel with polyelectrolyte complexes of aldehyde-modified chondroitin sulfate and gelatin: An approach for minocycline delivery.

Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.

Conformational Transition of Semiflexible Ring Polyelectrolyte in Tetravalent Salt Solutions: A Simple Numerical Modeling without the Effect of Twisting.

In this work, the conformational behaviors of ring polyelectrolyte in tetravalent salt solutions are discussed in detail through molecular dynamics simulation. For simplification, here we have neglected the effect of the twisting interaction, although it has been well known that both bending and twisting interactions play a deterministic in the steric conformation of a semiflexible ring polymer. The salt concentration CS and the bending energy b take a decisive role in the conformation of the ring polyelectrolyte (PE). Throughout our calculations, the b varies from b = 0 (freely joint chain) to b = 120. The salt concentration CS changes in the range of 3.56 × 10-4 M ≤ CS ≤ 2.49 × 10-1 M. Upon the addition of salt, ring PE contracts at first, subsequently re-expands. More abundant conformations are observed for a semiflexible ring PE. For b = 10, the conformation of semiflexible ring PE shifts from the loop to two-racquet-head spindle, then it condenses into toroid, finally arranges into coil with the increase of CS. As b increases further, four phase transitions are observed. The latter two phase transitions are different. The semiflexible ring PE experiences transformation from toroid to two racquet head spindle, finally to loop in the latter two phase transitions. Its conformation is determined by the competition among the bending energy, cation-bridge, and entropy. Combined, our findings indicate that the conformations of semiflexible ring PE can be controlled by changing the salt concentration and chain stiffness.

Incorporation of CuS nanorods in polyelectrolyte multilayer microcapsules improved cancer cell cytotoxicity and signal intensity in ultrasound imaging.

The fabrications of hollow microcapsules (MCs) with new architecture and ability to incorporate different nanomaterials have received great interest for targeted cancer therapy. Recently, CuS based nanomaterials have been demonstrated to possess the ability to mimic Fenton-like activity in tumor environment and inducing cancer cell apoptosis by generating highly reactive oxygen species (ROS). In this study, we have developed poly(allylamine) hydrochloride (PAH)/dextran sulfate (DS) polyelectrolyte MCs capable of carrying doxorubicin (DOX) for targeted cancer therapy and ultrasound imaging. The electron microscopy investigations showed the formation of polymeric MCs of 3 µm in size with incorporated CuS NRs in their interior structure. The surface modification of MCs with folic acid (FA), and encapsulation of model hydrophilic molecules in MCs was studied by UV-Visible (UV-Vis) spectroscopy, Fourier transform infra-red (FTIR) spectroscopy and confocal laser scanning microscopy. The encapsulation efficiency of DOX was found to be 56 % and the release was found to be linear at pH 5.5 and 7.4 in the absence of ultrasound exposure. The ultrasound exposure resulted in sudden rupture of MCs at 1 MHz and 1 W/cm2 and caused burst release of DOX at both pH conditions. The FA decorated PAH/DS/CuS NR MCs exhibited improved anti-cancer activity against MDA-MB-231 cancer cells due to the synergistic effects of ultrasound mediated burst release of chemotherapeutic drug (DOX), glutathione-stimulated ROS and targeted cancer therapy. Further, the capsules showed better echogenicity than that of control PAH/DS MCs when imaged under medical ultrasound-scanning system. Hence, the MCs demonstrated in this study have huge potential for targeted cancer theranostics by offering an option to image the cancer cells during the treatment period.

Supramolecular assembly of polycation/mRNA nanoparticles and in vivo monocyte programming.

Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces. Specifically, our strategy permits controlled assembly of small poly(ß-amino ester)/messenger ribonucleic acid (mRNA) nanoparticles into particles with a size that is kinetically tunable between 200 and 1,000 nm with high colloidal stability in physiological media. We found that assembled particles with an average size of 400 nm safely and most efficiently transfect monocytes following intravenous administration and mediate their differentiation into macrophages in the periphery. When a CpG adjuvant is co-loaded into the particles with an antigen mRNA, the monocytes differentiate into inflammatory dendritic cells and prime adaptive anticancer immunity in the tumor-draining lymph node. This platform technology offers a unique ligand-independent, particle-size-mediated strategy for preferential mRNA delivery and enables therapeutic paradigms via monocyte programming.

Chitosan-based biopolyelectrolyte complexes intercalated montmorillonite: A strategy for green flame retardant and mechanical reinforcement of polypropylene composites.

Due to dwindling petroleum resources and the need for environmental protection, the development of bio-based flame retardants has received much attention. In order to explore the feasibility of fully biomass polyelectrolyte complexes (PEC) for polyolefin flame retardant applications, chitosan (CS), sodium alginate (SA), and sodium phytate (SP) were used to prepare CS-based fully biomass PEC intercalated montmorillonite (MMT) hybrid biomaterials (SA-CS@MMT and SP-CS@MMT). The effects of two hybrid biomaterials on the fire safety and mechanical properties of intumescent flame-retardant polypropylene (PP) composites were compared. The SP-CS@MMT showed the best flame retardancy and toughening effect at the same addition amount. After adding 5 wt% SP-CS@MMT, the limiting oxygen index (LOI) value of PP5 reached 30.9 %, and the peak heat release rate (pHRR) decreased from 1348 kW/m2 to 163 kW/m2. In addition, the hydrogen bonding between polyelectrolyte complexes significantly improved the mechanical properties of PP composites. Compared with PP2, the tensile strength of PP5 increased by 59 %. This study provided an efficient and eco-friendly strategy for the large-scale production of renewable biomaterials with good thermal stability and expanded the application of macromolecular biomaterials in the field of fire safety.

Lidocaine HCl-Loaded Polyelectrolyte Complex -Poloxamer Thermoresponsive Hydrogel: In Vitro- In Vivo Anesthetic Evaluations for Tooth Socket Wound Delivery.

Local anesthesia is essential in dental practices, particularly for managing pain in tooth socket wounds, yet improving drug delivery systems remains a significant challenge. This study explored the physicochemical characteristics of lidocaine hydrochloride (LH) incorporated into a polyelectrolyte complex and poloxamer thermosensitivity hydrogel, assessing its local anesthetic efficacy in mouse models and its onset and duration of action as topical anesthetics in clinical trials. The thermoresponsive hydrogel exhibited a rapid phase transition within 1-3 minutes and demonstrated pseudo-plastic flow behavior. Its release kinetics followed Korsmeyer-Peppas, with 50% of biodegradation occurring over 48 h. In mouse models, certain thermogels showed superior anesthetic effects, with rapid onset and prolonged action, as evidenced by heat tolerance in tail-flick and hot plate models. In clinical trials, the LH-loaded thermoresponsive hydrogel provided rapid numbness onset, with anesthesia (Ton) beginning at an average of 46.5 ± 22.5 seconds and lasting effectively (Teff) for 202.5 ± 41.0 seconds, ranging from 120 to 240 seconds, indicating sustained release. These results highlight the promising properties of these formulations: rapid onset, prolonged duration, mucoadhesion, biodegradability, and high anesthesia effectiveness. This study demonstrates the potential for advancing local anesthesia across various medical fields, emphasizing the synergy between material science and clinical applications to improve patient care and safety.

A photothermal surface modified with polyelectrolyte multilayers for gene transfection and cell harvest.

Gene transfection, which involves introducing nucleic acids into cells, is a pivotal technology in the life sciences and medical fields, particularly in gene therapy. Surface-mediated transfection, primarily targeting cells adhering to surfaces, shows promise for enhancing cell transfection by localizing and presenting surface-bound nucleic acids directly to the cells. However, optimizing endocytosis for efficient delivery remains a persistent challenge. Additionally, ensuring efficient and non-traumatic cell harvest capability is crucial for applications such as ex vivo cell-based therapy. To address these challenges, we developed a photothermal platform with enzymatic degradation capability for efficient gene transfection and cell harvest. This platform is based on carbon nanotubes (CNTs) doped with poly(dimethylsiloxane) and modified with polyelectrolyte multilayers (PEMs) containing hyaluronic acid and quaternized chitosan, allowing for substantial loading of poly(ethyleneimine)/plasmid DNA (pDNA) complexes through electrostatic interactions. Upon irradiation of near-infrared laser, the photothermal properties of CNTs enable high transfection efficiency by delivering pDNA into attached cells via a membrane disruption mechanism. The engineered cells can be harvested by treating with a non-toxic hyaluronidase solution to degrade PEMs, thus maintaining good viability for further applications. This platform has demonstrated remarkable efficacy across various cell lines (including Hep-G2 cells, Ramos cells and primary T cells), achieving a transfection efficiency exceeding 95 %, cell viability exceeding 90 %, and release efficiency surpassing 95 %, highlighting its potential for engineering living cells.

Compaction, Relaxation, and Linearization of Megadalton-Sized DNA Plasmids: DNA Structures Probed by CD-MS.

High purity plasmid DNA is a raw material for recombinant protein production as well as an active ingredient in DNA vaccines. There are four primary plasmid structures that can be observed in a typical plasmid formulation: supercoiled, relaxed (circular), linearized, and condensed. Determining what structures are present in a sample is important, as the structure can affect activity; the supercoiled structure has the highest activity, and >90% supercoiled is desired for industry standards. Recently, charge detection mass spectrometry (CD-MS) was used to distinguish two of the structures, supercoiled and condensed, by measuring the charge deposited on the ions by positive mode electrospray. Here, CD-MS is used to probe the structures of DNA plasmids during compaction with polycations, and through enzymatic treatment to relax and linearize plasmids. We find that all four structural types for plasmid DNA have unique charging profiles that can be distinguished using CD-MS. The extent of mechanical shearing of the DNA plasmids during electrospray is strongly influenced by the structural type.

Cytotoxicity and antibacterial susceptibility assessment of a newly developed pectin-chitosan polyelectrolyte composite for dental implants.

Biopolymers such as chitosan and pectin are currently attracting significant attention because of their unique properties, which are valuable in the food industry and pharmaceutical applications. These properties include non-toxicity, compatibility with biological systems, natural decomposition ability, and structural adaptability. The objective of this study was to assess the performance of two different ratios of pectin-chitosan polyelectrolyte composite (PCPC) after applying them as a coating to commercially pure titanium (CpTi) substrates using electrospraying. The PCPC was studied in ratios of 1:2 and 1:3, while the control group consisted of CpTi substrates without any coating. The pull-off adhesion strength, cytotoxicity, and antibacterial susceptibility tests were utilized to evaluate the PCPC coatings. In order to determine whether the composite coating was the result of physical blending or chemical bonding, the topographic surface parameters were studied using Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). PCPC (1:3) had the highest average cell viability of 93.42, 89.88, and 86.85% after 24, 48, and 72 h, respectively, as determined by the cytotoxicity assay, when compared to the other groups. According to the Kirby-Bauer disk diffusion method for testing antibacterial susceptibility, PCPC (1:3) showed the highest average diameter of the zone of inhibition, measuring 14.88, 14.43, and 11.03 mm after 24, 48, and 72 h of incubation, respectively. This difference was highly significant compared to Group 3 at all three time periods. PCPC (1:3) exhibited a significantly higher mean pull-off adhesion strength (521.6 psi) compared to PCPC (1:2), which revealed 419.5 psi. PCPC (1:3) coated substrates exhibited better surface roughness parameters compared to other groups based on the findings of the AFM. The FTIR measurement indicated that both PCPC groups exhibited a purely physical blending in the composite coating. Based on the extent of these successful in vitro experiments, PCPC (1:3) demonstrates its potential as an effective coating layer. Therefore, the findings of this study pave the way for using newly developed PCPC after electrospraying coating on CpTi for dental implants.

Nanoassemblies of Chitosan-Based Polyelectrolyte Complexes as Nucleic Acid Delivery Systems.

Nucleic acid delivery requires vectorization for protection from nucleases, preventing clearance by the reticuloendothelial system, and targeting to allow cellular uptake. Nanovectors meeting the above specifications should be safe for the patient, simple to manufacture, and display long-term stability. Our nanovectors were obtained via the green process of polyelectrolyte complexation, carried out at 25 °C in water at a low shear rate using chitosan (a polycationic biocompatible polysaccharide of specific molar mass and acetylation degree) and dextran sulfate as a polyanionic biocompatible polysaccharide. These complexes formed nanoassemblies of primary nanoparticles (20-35 nm) and maintained their colloidal stability for over 1 year at 25 °C. They could be steam sterilized, and a model nucleic acid could be either encapsulated or surface adsorbed. A targeting agent was finally bound to their surface. This work serves as a proof of concept of the suitability of chitosan-based polyelectrolyte complexes as nanovectors by sequential multilayered adsorption of various biomacromolecules.

Cell-penetrating activity of a short-chain ε-poly-l-α-lysine.

Bacteria produce polycationic homopoly(amino acid)s, which are characterized by isopeptide backbones. We previously demonstrated that two representative bacterial polycationic isopeptides, ε-poly-l-α-lysine consisting of 25-35 l-α-lysine residues (ε-PαL25-35) and ε-poly-l-ß-lysine consisting of l-ß-lysine residues (ε-PßL4-13), were internalized into mammalian cells by both energy-independent direct penetration and energy-dependent endocytosis/macropinocytosis, and then diffused throughout the cytosol. In this study, we investigated the cell-penetrating activity of an ε-PαL short-chain derivative consisting of 5-14 l-α-lysine residues (ε-PαL5-14) to gain insight into the relationship between the isopeptide-chain length and the manner of cellular internalization. We prepared a conjugate of ε-PαL5-14 and a fluorescent dye (FAM) by click chemistry, and incubated the resulting polymer, ε-PαL5-14-FAM, with HeLa cells. Unlike ε-PαL25-35-FAM, ε-PαL5-14-FAM was internalized into cells only by energy-dependent endocytosis/macropinocytosis. Furthermore, a high concentration (>50 µM) was required for the internalization events. ε-PαL5-14 has a chain length almost equal to that of the membrane permeable ε-PßL4-13, which can enter cells at low concentrations. Considering that the basicity of the ß-amino group is higher than that of α-amino acid at physiological pH, ε-PßL is expected to have a greater cell-penetrating capacity than ε-PαL, provided their isopeptide-chain lengths are similar, suggesting that a more extended chain derivative of ε-PßL would be more advantageous for cellular internalization of cargo proteins than ε-PαL25-35.

Zwitterionic Polyelectrolyte Complex Vesicles Assembled from Homopoly(2-Oxazoline)s as Enzyme Catalytic Nanoreactors for Potent Anti-Tumor Efficiency.

Enzymes are known for their remarkable catalytic efficiency across a wide range of applications. Here, we present a novel and convenient nanoreactor platform based on zwitterionic polyelectrolyte complex vesicles (PCVs), assembled from oppositely charged homopoly(2-oxazoline)s, facilitating enzyme immobilization. We show remarkable enhancements in catalytic activity and stability by encapsulation of lipase as a model enzyme. Even as the temperature rises, the performance of the lipase remains robust. Further, the structural characteristics of PCVs, including hollow architecture and semipermeable membranes, endow them with unique advantages for enzyme cascade reactions involving glucose oxidase (GOx) and horseradish peroxidase (HRP). A decline in catalytic efficiency is shown when the enzymes are individually loaded and subsequently mixed, in contrast to the coloaded GOx-HRP-PCV group. We demonstrate that the vesicle structures establish confined environments where precise enzyme-substrate interactions facilitate enhanced catalytic efficiency. In addition, the nanoreactors exhibit excellent biocompatibility and efficient anti-tumor activity, which hold significant promise for biomedical applications within enzyme-based technologies.

Biodegradable Microembolics with Nanografted Polyanions Enable High-Efficiency Drug Loading and Sustained Deep-Tumor Drug Penetration for Locoregional Chemoembolization Treatment.

Transarterial chemoembolization (TACE), the mainstay treatment of unresectable primary liver cancer that primarily employs nondegradable drug-loaded embolic agents to achieve synergistic vascular embolization and locoregional chemotherapy effects, suffers from an inferior drug burst behavior lacking long-term drug release controllability that severely limits the TACE efficacy. Here we developed gelatin-based drug-eluting microembolics grafted with nanosized poly(acrylic acid) serving as a biodegradable ion-exchange platform that leverages a counterion condensation effect to achieve high-efficiency electrostatic drug loading with electropositive drugs such as doxorubicin (i.e., drug loading capacity >34 mg/mL, encapsulation efficiency >98%, and loading time <10 min) and an enzymatic surface-erosion degradation pattern (∼2 months) to offer sustained locoregional pharmacokinetics with long-lasting deep-tumor retention capability for TACE treatment. The microembolics demonstrated facile microcatheter deliverability in a healthy porcine liver embolization model, superior tumor-killing capacity in a rabbit VX2 liver cancer embolization model, and stabilized extravascular drug penetration depth (>3 mm for 3 months) in a rabbit ear embolization model. Importantly, the microembolics finally exhibited vessel remodeling-induced permanent embolization with minimal inflammation responses after complete degradation. Such a biodegradable ion-exchange drug carrier provides an effective and versatile strategy for enhancing long-term therapeutic responses of various local chemotherapy treatments.

Chitosan-alginate/R8 ternary polyelectrolyte complex as an oral protein-based vaccine candidate induce effective mucosal immune responses.

Vaccination is the most effective method for preventing infectious diseases. Oral vaccinations have attracted much attention due to the ability to boost intestinal and systemic immunity. The focus of this study was to develop a poly (lactide-co-glycolide) acid (PLGA)-based ternary polyelectrolyte complex (PEC) with chitosan, sodium alginate, and transmembrane peptides R8 for the delivery of antigen proteins. In this study, the antigen protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis (MAP) antigens HBHA, Ag85B, and Bfra, was combined with R8 to generate self-assembled conjugates. The results showed that PEC presented a cross-linked reticular structure to protect the encapsulated proteins in the simulated gastric fluid. Then, the nanocomposite separated into individual nanoparticles after entering the simulated intestinal fluid. The ternary PEC with R8 promoted the in vivo uptake of antigens by intestinal lymphoid tissue. Moreover, the ternary PEC administered orally to mice promoted the secretion of specific antibodies and intestinal mucosal IgA. In addition, in the mouse models of MAP infection, the ternary PEC enhanced splenic T cell responses, thus reducing bacterial load and liver pathology score. These results suggested that this ternary electrolyte complex could be a promising delivery platform for oral subunit vaccine candidates, not limited to MAP infection.

Preparation of photothermal alginate/chitosan derivative/CuS@polydopamine composite fibers and application in desalination.

A polyelectrolyte system consisting of sodium alginate (SA) and quaternary ammonium chitosan (QAC) blended with polydopamine-coated copper sulfide particles (CuS@PDA) was chosen to investigate the function of CuS@PDA in the uniform binary blending of anionic and cationic polyelectrolytes in detail. A smart composite fiber SA/QAC/CuS@PDA was prepared via a dry-wet spinning technique. With the addition of CuS@PDA (about 4.3 % in fiber), the as-prepared SA/QAC/CuS@PDA-0.50 fibers (SQCuS@P-0.50 SCFs) showed notably enhanced intensity 359.2 MPa, excellent moisture response, and photothermal conversion performance, with the temperature increasing from 25.9 to 80.7 °C as irradiated under a 980 nm infrared lamp at distance 20 cm away for 120 s. The photothermal performance was maintained after 6 lighting on-and-off cycles. The tensile strength decreased ~23.8 % after 4 cycles, then remained fixed. The diameter increases to ~480 % in wet state but decreases to the original size in dry state for 10 cycles. When the fabric with 90 wt% SQCuS@P-0.50 SCFs was used as a water evaporator, the water evaporation rate and efficiency were 1.68 kg·m-2·h-1 and 102 % under 1 sun irradiation. This work provides a simple and ecofriendly strategy for fabricating photothermal fabrics by designing and preparing composite fibers.

Natural and polyanionic heparin polysaccharide functionalized upconversion nanoparticles for highly sensitive and selective ratiometric detection of pesticide.

Pesticide contamination is a global concern, threatening human health and food safety. Herein, we developed heparin (HEP) functionalized upconversion nanoparticles (UCNPs)-based ratiometric nanosensor for the sensitive detection of 2,6-dichloro-4-nitroaniline (DCN) pesticide via inner filter effect. The strategy for HEP functionalization of UCNPs is based on adjusting the surface potentials of UCNPs with polyanionic HEP through the electrostatic interaction. UCNPs (NaYbF4:Gd/Y/Tm@NaYbF4@NaYF4) was designed with core-shell-shell structure and extra sensitizer layer for efficient and strong upconversion luminescence (UCL) in the range of UV to NIR. After incorporation of DCN, the upconverted UV emission of UCNPs-HEP ratiometric nanosensor was considerably quenched with the NIR UCL at 800 nm remaining unchanged as internal standard. The UCNPs-HEP ratiometric nanosensor can achieve outstandingly selective and sensitive detection of DCN at the wide linear range of 5-300 µM with a detection limit of 0.41 µM. The remarkable applicability of the UCNPs-HEP ratiometric nanosensor was verified in apple, cucumber and grapes samples. The developed UCNPs-HEP ratiometric nanosensor with excellent biocompatibility and water dispersion capability, is promising for convenient, selective and sensitive sensing of DCN towards food and aqueous samples.

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

AIM: Atorvastatin (ATO) loaded chitosan-based polyelectrolyte complex nanoparticles (PECN) incorporated transdermal patch was developed to enhance its skin permeability and bioavailability. METHODOLOGY: The 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. RESULTS: The 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. CONCLUSIONS: The results of the present work concluded that the ATO-PECN loaded transdermal patch is a promising novel drug delivery system for poorly bioavailable drugs.

Polyelectrolyte-coated liposomes microfluidically assembled in one-step for enhancing cell endocytosis and in-vivo immune responses.

To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.