Hybrid Nanoparticles Research Articles

Development, Characterization, and Antimicrobial Evaluation of Hybrid Nanoparticles (HNPs) Based on Phospholipids, Cholesterol, Colistin, and Chitosan Against Multidrug-Resistant Gram-Negative Bacteria

Background: Colistin, a lipopeptide antibiotic usually used as a last resort against multidrug-resistant bacterial strains, has also begun to address the challenge of antimicrobial resistance. Objective: this study evaluates whether hybrid nanoparticles (HNPs) composed of Phospholipon® 90G, cholesterol, and colistin can enhance its effectiveness against resistant clinical isolates of Klebsiella pneumoniae, a clinically significant Gram-negative bacterium. Methods: HNPs were developed using the ethanol injection method and coated with chitosan through a layer-by-layer technique. HNP characterization included measurements of particle size, polydispersity index (PDI), and zeta potential, along with thermal (DSC) and spectrophotometric (FT-IR) analyses. Ultrafiltration and ATR-FTIR were employed to assess colistin’s association and release efficiencies. The biological evaluation followed CLSI guidelines. Results: uncoated hybrid nanoparticles (U-HNP) and chitosan-coated hybrid nanoparticles (Ch-HNP) described monodisperse populations, with respective PDI values of ~0.124 and ~0.150, Z-averages of ~249 nm and ~250 nm, and zeta potential values of +17 mV and +20 mV. Colistin’s association and release efficiencies were approximately 79% and 10%, respectively. Regarding antimicrobial activity, results showed that colistin as part of HNPs is poorly effective against this microorganism. However, in the most resistant strain, colistin activity increased slightly when the HNP was coated with chitosan. Conclusions: HNPs described high stability against disaggregation, limiting the colistin release and, therefore, affecting antimicrobial performance.

Multistage microfluidic assisted Co-Delivery platform for dual-agent facile sequential encapsulation.

The integration of multiple therapeutic agents within a single nano-drug carrier holds promise for advancing anti-tumor therapies, despite challenges posed by their diverse physicochemical properties. This study introduces a novel multi-stage microfluidic co-encapsulation platform designed to address these challenges. By carefully orchestrating the nano-precipitation process sequence, this platform achieves sequential encapsulation of two drugs with markedly different physicochemical characteristics. Using the multi-stage microfluidic TrH chip, hybrid nanoparticles (HNPs) loaded with paclitaxel (PTX)-simvastatin (SV), PTX-lenvatinib (LV), and SV-LV were synthesized. Unlike conventional Bulk methods and existing commercial microfluidic Tesla and Baffle chips, the HNPs produced here exhibit a core-shell structure and uniform particle size distribution, crucial for enhancing drug delivery efficacy. Notably, this method achieves nearly 100 % encapsulation efficiency for both drugs across a dual-drug feed ratio range from 1:4 to 4:1. Drug loading efficiencies were quantified for PTX-SV/HNPs (14.97 ± 1.19 %), PTX-LV/HNPs (16.58 ± 0.69 %), and SV-LV/HNPs (19.21 ± 2.38 %). PTX-SV/HNPs demonstrated sequential release characteristics of SV and PTX, as confirmed by in vitro drug release experiments. Significantly, PTX-SV/HNPs exhibited superior cytotoxicity against HepG2 cells compared to individual PTX and SV treatments, underscoring their potential in cancer therapy. In conclusion, the developed multi-stage microfluidic platform represents a robust strategy for co-encapsulating drugs with substantial physicochemical disparities, thereby offering a promising avenue for advancing multi-drug delivery in nanomedicine applications.

AI-led study of dynamic changes in milk containing hybrid nanoparticles in an electromagnetically vibrated channel subjected to thermal oscillations and rapid pressure changes: Implications for dairy industry

Oscillating electromagnetic forces generated from a vibrated Riga plate have broad implications across various scientific and engineering domains. Artificial intelligence (AI) is applied to optimize precision and energy efficiency in pasteurization and sterilization by regulating the thermal and dynamic behavior of nanoparticle-infused milk under electromagnetic heating. The technique ensures accurate temperature control, minimizes the risk of overheating, and preserves the milk's nutritional and sensory qualities. It focuses on predicting the thermal and dynamic behaviors of milk infused with silver and zinc oxide nanoparticles in an electromagnetically vibrated channel experiencing thermal oscillations and rapid pressure changes. The research integrates complex physical phenomena such as radiant heat emission and Darcy drag forces, employing Darcy's model to delve into drag within porous media. Detailed mathematical and physical descriptions of milk flow dynamics are established, with solutions efficiently derived using the Laplace Transform (LT) method. The results, encompassing shear stress (SS) and rate of heat transfer (RHT) analyses, are detailed in tables and graphs. Findings indicate enhanced milk momentum with higher modified Hartmann number and reduced momentum with wider electrode spacing. Elevated oscillation frequencies of the left channel wall stabilize milk flow in both hybrid nano-milk (HNM) and nano-milk (NM). Larger Casson parameter improves SS, while higher radiation parameter reduces RHT. An AI-driven artificial neural network (ANN) is employed for precise estimations, achieving 98.022% accuracy in SS testing, 98.99% in cross-validation, and a flawless 100% accuracy for RHT. The research findings can be implemented to precisely control the mixing of milk and its physical features at a molecular level, enabling more even heat distribution and faster, more efficient pasteurization or homogenization processes.

Nanoparticle-mediated enhancement of DNA Vaccines: Revolutionizing immunization strategies.

DNA vaccines are a novel form of vaccination that aims to harness genetic material to produce targeted immune responses. Nevertheless, their therapeutic application is hampered by low transfection efficacy, immunogenicity, and instability. Nanoparticle (NP) - based delivery systems are beneficial in enhancing DNA stability, increasing DNA uptake by antigen-presenting cells (APCs), and controlling antigen release. Some key progress includes the polymeric, lipid-based, and hybrid NPs and biocompatible carriers with inherent adjuvant effects. These systems have helped to enhance the antigen cross-presentation and T-cell activation significantly. In addition, biocompatible hybrid nanocarriers, antigen cross-presentation strategies, and next-generation sequencing (NGS) technologies are speeding up the identification of new antigens, while AI and machine learning are facilitating the development of efficient delivery systems. This review aims to assess how NPs have contributed to improving the effectiveness of DNA vaccines for treating diseases, cancer, and emerging diseases, as well as advancing the next generation of DNA vaccines.

Intradermal versus subcutaneous immunization: Effects of administration route using a lipid-PLGA hybrid nanoparticle tuberculosis vaccine.

Tuberculosis (TB) remains a significant global health challenge, latently affecting around a quarter of the global population. The sole licensed TB vaccine, Mycobacterium bovis Bacillus Calmette-Guérin (BCG), shows variable efficacy, particularly among adolescents and adults, underscoring the pressing need for more effective vaccination strategies. The administration route is crucial for vaccine efficacy, and administration via the skin, being rich in immune cells, may offer advantages over conventional subcutaneous routes, which lack direct access to abundant antigen-presenting cells. This study compared the immunogenic effects of intradermal versus subcutaneous administration of a candidate TB vaccine delivering a Ag85B-ESAT6-Rv2034 (AER) multiphase fusion recombinant protein, in lipid-poly(D,L-lactic-co-glycolic acid) (lipid-PLGA) nanoparticles in mice. In-depth evaluation of immune responses in splenocytes was performed using 27-marker spectral flow cytometry. Both routes elicited significant T-cell responses. However, intradermal administration uniquely increased polyfunctional CD4+ and CD8+ T-cells producing IL-2, IFNγ, and TNFα, associated with protection against TB. Additionally, it significantly increased CD69+ B-cell counts and induced higher AER-specific antibody titers, particularly IgG2a. These results underscore the superior immunogenic potential of intradermal vaccine administration by effectively inducing immune cells associated with TB protection, highlighting its significance in the development of new vaccine strategies.

Controllable surface carrier type of metal oxide nanocrystals for multifunctional photocatalysis.

Selectively harnessing photo-induced carriers to control surface photo-redox reactions can enable currently limited specificity in photocatalytic applications. By using a new approach to switching between dominant electron and hole charge transfer on the surfaces of metal oxide nanocrystals, depending on the optimal carrier for specific application functionality in photocatalytic pollutant degradation, H2 production, CO2 reduction, and gas sensing. The approach is based on the surface redox properties of custom-designed p-n hetero-structured hybrid nanoparticles (NPs) containing copper oxide, and wide-gap metal oxide semiconductors (MOSs). The customized CuxO/ZnO (CXZ) heterostructures ensure effective charge separation and surface reactions driven by UV-vis excited highly reactive holes and show high performance in the photo-oxidative degradation of organic dyes and NO2 gas sensing. By switching the dominant surface carrier type from holes to electrons, the hybrids exhibit excellent performance in photocatalytic H2 evolution and CO2 reduction. This work offers a generic approach to engineering multipurpose photocatalytic materials.

Intracellular MRSA-targeted lipid-polymer hybrid nanoparticles for macrophage reprogramming and intracellular MRSA eradication

Intracellular MRSA-targeted lipid-polymer hybrid nanoparticles for macrophage reprogramming and intracellular MRSA eradication

Analysis of Blood Flow Features in the Curved Artery in the Presence of Differently Shaped Hybrid Nanoparticles

Analysis of Blood Flow Features in the Curved Artery in the Presence of Differently Shaped Hybrid Nanoparticles

Co-delivery of vinorelbine and rutin by lipid polymer nanoparticles for enhanced liver cancer chemotherapy

The purpose of this study was to develop a lipid polymer hybrid nanoparticle (LPNs) for the codelivery of Vinorelbine (VBL) and Rutin (RUT) for the treatment of hepatic carcinoma. The VBL loaded LPNs (VBL-LPNs), and VBL and RUT loaded LPNs (VBL-RUT-LPNs) were prepared using PLGA (polymer) and dynasan 114 (lipid) by probe sonication and high pressure homogenization method. The VBL-LPNs and VBL-RUT-LPNs exhibited a particle size (260±5.40 and 298±3.51 nm), PDI (0.312±0.03 and 0.286±0.03), ZP (-18.8±2.60 and -19.8±2.70 mV), EE (73.7±1.52 and 77.9±2.19%) and LC (2.3±0.49 and 2.5±0.73%), respectively. In-vitro release studies exhibited a sustained release patter for 48 hours, with korsmayer peppas kinetics model. No significatnt changes in VBL-LPNs and VBL-RUT-LPNs was confirmed by stability studies. As compared to free VBL and VBL-LPNs, we observed increased cytotoxicity and lowered inhibitory concentration IC50 in HepG2 cells treated with VBL-RUT-LPNs, indicating the synergistic effects of VBL and RUT. The VBL-RUT-LPNs also upregulated caspase 3 and downregulated Bcl-2, indicating a successful apoptosis. When combined, VBL and RUT are delivered concurrently by VBL-RUT-LPNs, which may offer a promising treatment for hepatic carcinoma.

Bacterial cellulose/thiolated chitosan nanoparticles hybrid antimicrobial dressing for curcumin delivery.

Thiolated chitosan (Cs-SH) nanoparticles were synthesized and incorporated into bacterial cellulose (BC) membranes through vacuum-assisted confinement. Thiolation significantly enhanced the intrinsic adhesion capacity of chitosan (Cs) as well as its solubility in neutral aqueous solutions. Subsequently, Cs-SH nanoparticles were successfully loaded with curcumin (Cur-Cs-SH), with nanoparticle sizes of 121±2nm for Cs-SH and 152±6nm for Cur-Cs-SH. Stability assessments revealed improved pH tolerance and colloidal stability due to the introduction of thiol groups and curcumin encapsulation. Notably, the retention yield of nanoparticles in BC was calculated to be 99% (w/v) within 45min. Nanoparticle and curcumin in vitro release studies demonstrated pH-dependent profiles, indicating controlled release kinetics influenced by initial loading and environmental acidity. Moreover, the enhanced adhesive properties of the developed BC membranes, verified by mucin disks and porcine skin adhesion tests, suggested their potential for targeted drug delivery to human tissue. Additionally, antimicrobial assays suggested a synergistic effect between Cs-SH and encapsulated curcumin, exhibiting antibacterial activity against S. aureus and E. coli. In this research, the bioavailability of curcumin was increased by encapsulating it in Cur-Cs-SH nanoparticles, which enhanced its antimicrobial properties and improved the adhesion of BC membranes, thereby expanding their applications in biomedicine.

Enhancement of Hydrogen Production Using an Integrated Evacuated Tube Solar Collector and PEM Electrolyzer With Al2O3 and SiO2 Hybrid Nanofluids

ABSTRACTThe motivation for this study stems from the global demand for clean energy solutions and the limitations of conventional fluids in hydrogen production systems. By exploring hybrid nanofluids, this research aims to enhance efficiency and sustainability in solar‐thermal energy applications. An evacuated tube solar collector (ETSC) with a polymer electrolyte membrane (PEM) electrolyzer efficiently harnesses solar energy for hydrogen production. The ETSC's vacuum design minimizes heat loss, providing consistent thermal performance. This system enables clean hydrogen generation, reducing emissions. This study investigated the integration of an ETSC with a PEM electrolyzer and organic Rankine cycle (ORC) for efficient hydrogen production. Water as the working fluid in the ETSC circuit resulted in lower hydrogen production rates, prompting the introduction of Al2O3 and SiO2 hybrid nanoparticles at a 50:50 ratio to form an enhanced hybrid nanofluid. The resulting various volume concentrations (0.5%, 1%, 1.5%, and 2%) of the hybrid nanofluid were tested, yielding energy gains of 13.22%, 21.37%, 30.38%, and 48.52%, respectively, compared to water. The ORC efficiency enhanced by 12.29% at 0.5 vol.%, 23.10% at 1 vol.%, 34.15% at 1.5 vol.%, and 48.40% at 2 vol.%. The PEM electrolyzer produced a maximum hydrogen yield of 3105.6 g, with an overall system efficiency of 71.3% and hydrogen production of 2156.7 g at 2 vol.%, demonstrating the significant performance enhancements achieved with hybrid nanofluids. The results demonstrated the effectiveness of hybrid nanofluids in enhancing system efficiency and hydrogen output, underscoring their importance in promoting sustainable hydrogen production technologies.

Thermal performance of Falkner Skan model (FSM) for (GOMoS2)/(C2H6O2-H2O) 50:50% nanofluid under radiation heating source

The hybrid base solvent water (H2O) and ethylene glycol (C2H6O2) are highly use in industrial applications due to excellent solvability. Addition of hybrid nanoparticles (GO-MoS2) augments the thermal conductivity of these fluids which ultimately make them very productive. Hence, the current study aims to develop and investigate the novel hybrid nanofluid model (GO-MoS2)/(C2H6O2-H2O) through MRW (moving riga wedge) and SRW (static riga wedge) cases. The traditional Falkner Skan Model (FSM) is modified using the novel effects of solar radiations, internal heating source and fixed magnets which is associated to the concept of Riga wedge. Further, the improved thermal-physical characteristics of hybrid nanofluids will use to enhance the thermal productivity. A mathematical model is developed for the flow situation of (GO-MoS2)/(C2H6O2-H2O) and treated numerically. The results furnished through graphical way and comprehensive discussion provided. It is examined that the movement of (GO-MoS2)/(C2H6O2-H2O) reduced for MRW and observed the rapid velocity near the surface. The heat generating source and solar radiations number enhanced the performance of (GO-MoS2)/(C2H6O2-H2O) and better predicted ranges for these parameters are observed from and . Moreover, the boundary layer region becomes thin for heating source and it increased for stronger solar radiation effects. The nanoparticle amount of GO and MoS2 enhanced the model utilization while higher magnetic number and MRW number controlled the thermal boundary layer. The results for the model dynamics are noticed dominant for MRW case as compared to SRW case.

Adsorption Isotherm Analysis for Hybrid Molecularly Imprinted Polymeric Gold-Decorated Nanoparticles Suitable for Reliable Quantification of Gluconic Acid in Wine

A class of hybrid molecularly imprinted polymeric nanoparticles (nanoMIPs) comprising the in situ formation of gold nanoparticles (AuNPs) immobilised in a molecularly imprinted D-gluconate polymer has been designed with the objective of attempting the electrochemical quantification of gluconic acid (GA) in a wine setting. The imprinted polymers were synthesised in the presence of AuNP precursors in a pre-polymerisation mixture, which were confined to one another during the polymerisation of the chains. This allowed the formation of hybrid electroactive responsive imprinted nanoparticles (hybrid AuNPs@GA-nanoMIP), which exhibited enhanced electron conductivity. The morphological characterisation of the produced nanoMIPs revealed a fully decorated Au spherical surface of 200 nm in diameter. This resulted in a large active surface area distribution, as well a pronounced electrochemical peak response at the commercial screen-printed platinum electrode (SPPtE), accompanied by enhanced electron kinetics. The AuNPs@GA-nanoMIP sensor demonstrated the ability to detect a broad range of GA concentrations (0.025–5 mg/mL) with exceptional selectivity and reproducibility. The calibration curves were fitted with different isotherm models, such as the Langmuir, Freundlich and Langmuir–Freundlich functions. Moreover, the efficacy of the detection method was demonstrated by the recovery rates observed in real samples of Italian red wine. This research contributes to the development of a robust and reliable electrochemical sensor for the on-site determination of gluconic acid in food analysis.

Orbital angular momentum light interacted with double quantum dot-metal nanoparticle hybrid structure under spontaneous coherence

This work studies the generation of the orbital angular momentum (OAM) beam in the double quantum dot-metal nanoparticle (DQD-MNP) system under the application of the OAM beam. First, an analytical model is derived to attain the relations of probe and generated fields as a distance function in the DQD-MNP system under OAM applied field and spontaneously generated coherence (SGC) components. The calculation here is of material property; it differs from others by calculating energy states of the DQDs and the computation of the transition momenta between quantum dot (QD)-QD and QD-wetting layer (WL) transitions. The orthogonalized plane wave (OPW) calculates QD-WL transitions and their momenta. The momentum calculation is essential to specify the Rabi frequency of the input field. Such characteristics are not used in earlier models. The results show that SGC is vital in increasing the generated field. The signal field generated in the DQD-MNP system doubles that from the DQD system alone. So, the DQD-MNP system is preferred to the DQD system. The generated field in the DQD-MNP for the strong coupling DQD-MNP system is higher than that for the weak coupling. Increasing the distance separating the DQD-MNP reduces the generated field. Higher OAM number reduce the generated field at a long distance in the device. The model is then extended to study the effect of incoherent pumping () and the relations are modified to cover this part. The results show that reduces the generated field. While the results that compare the weak and strong coupling appear for the first, others compare well to the literature.

Effects of Green-Synthesised Copper Oxide–Zinc Oxide Hybrid Nanoparticles on Antifungal Activity and Phytotoxicity of Aflatoxin B1 in Maize (Zea mays L.) Seed Germination

Maize contamination with aflatoxin B1 (AFB1) is of significance on a global scale due to its major contribution to food security. It is very probable that substantial amounts of AFB1 may be absorbed by germinating seeds grown in contaminated soil and cause deleterious effects on the growth and development of maize. In this study, the effect of green-synthesised ZnO-CuO hybrid nanoparticles (NPs) on antifungal activity and reducing the toxic effects of AFB1 on seed germination was examined. A notable inhibitory effect of green-synthesised ZnO-CuO nanoparticles (NPs) on A. flavus was observed at a concentration of 0.5 ppm, resulting in 13.1% inhibition, which was more effective than the higher concentration of 1.0 ppm and the control. The results showed that the final germination percentage of the seeds that were inoculated with 320 ppb was significantly increased by the treatment with 125 mg/mL of green ZnO-CuO hybrid NPs. This study indicated the potential of green-synthesised ZnO-CuO hybrid NPs as alternative antifungal agents to control aflatoxin production in maize to improve food security and safety by supressing the threat posed by AFB1.

Development, Characterization, and Evaluation of Chi-Tn mAb-Functionalized DOTAP-PLGA Hybrid Nanoparticles Loaded with Docetaxel for Lung Cancer Therapy

Background/Objectives: The focus of this study was to prepare and characterize docetaxel (DCX)-loaded lipid/polymer hybrid nanoparticles (LPHNps) functionalized with the monoclonal antibody (mAb) Chi-Tn for a potential active targeting approach in lung cancer treatment. Methods: We synthesized DOTAP-PLGA hybrid nanoparticles loaded with DCX and functionalized them with Chi-Tn mAb through a biotin–avidin approach. The physicochemical characterization involved dynamic light scattering, transmission electron microscopy, Raman spectroscopy, and atomic force microscopy. The in vitro and in vivo evaluations encompassed uptake studies, cell viability tests, and the assessment of tumor growth control in a lung cancer model. Results: The nanoparticles featured a hydrophobic PLGA core with 99.9% DCX encapsulation efficiency, surrounded by a DOTAP lipid shell ensuring colloidal stability with a high positive surface charge. The incorporation of PEGylated lipids on their surface helps evade the immune system and facilitate Chi-Tn mAb attachment. The resulting nanoparticles exhibit a spherical shape with monodisperse particle sizes averaging 250 nm, and demonstrate sustained drug release. In vitro uptake studies and viability assays conducted in A549 cancer cells show that the Chi-Tn mAb enhances nanoparticle internalization and significantly reduces cell viability. In vivo studies demonstrate a notable reduction in tumor volume and an increased survival rate in the A549 tumor xenograft mice model when DCX was encapsulated in nanoparticles and targeted with Chi-Tn mAb in comparison to the free drug. Conclusions: Therefore, Chi-Tn-functionalized LPHNps hold promise as carriers for actively targeting DCX to Tn-expressing carcinomas.

From Traditional Nanoparticles to Cluster-Triggered Emission Polymers for the Generation of Smart Nanotheranostics in Cancer Treatment

Nanotheranostics integrates diagnostic and therapeutic functionalities using nanoscale materials, advancing personalized medicine by enhancing treatment precision and reducing adverse effects. Key materials for nanotheranostics include metallic nanoparticles, quantum dots, carbon dots, lipid nanoparticles and polymer-based nanocarriers, each offering unique benefits alongside specific challenges. Polymer-based nanocarriers, including hybrid and superparamagnetic nanoparticles, improve stability and functionality but are complex to manufacture. Polymeric nanoparticles with aggregation-induced emission (AIE) present promising theranostic potential for cancer detection and treatment. However, challenges such as translating the AIE concept to living systems, addressing toxicity concerns, overcoming deep-tissue imaging limitations, or ensuring biocompatibility remain to be resolved. Recently, cluster-triggered emission (CTE) polymers have emerged as innovative materials in nanotheranostics, offering enhanced fluorescence and biocompatibility. These polymers exhibit increased fluorescence intensity upon aggregation, making them highly sensitive for imaging and therapeutic applications. CTE nanoparticles, crafted from biodegradable polymers, represent a safer alternative to traditional nanotheranostics that rely on embedding conventional fluorophores or metal-based agents. This advancement significantly reduces potential toxicity while enhancing biocompatibility. The intrinsic fluorescence allows real-time monitoring of drug distribution and activity, optimizing therapeutic efficacy. Despite their potential, these systems face challenges such as maintaining stability under physiological conditions and addressing the need for comprehensive safety and efficacy studies to meet clinical and regulatory standards. Nevertheless, their unique properties position CTE nanoparticles as promising candidates for advancing theranostic strategies in personalized medicine, bridging diagnostic and therapeutic functionalities in innovative ways.

Mathematical modelling of MHD hybrid nanofluid flow in a convergent and divergent channel under variable thermal conductivity effect

Abstract The aim of this research is to analyse the combined effect of variable thermal conductivity and nonlinear thermal radiation on magnetohydrodynamic (MHD) hybrid nanofluid flow in convergent-divergent channels. The effects of two nanoparticles (i.e. ZrO 2 {\text{ZrO}}_{\text{2}} and SiO 2 {\text{SiO}}_{\text{2}} ) in base fluid (i.e. H 2 O {\text{H}}_{\text{2}}\text{O} ) are considered in this work. The partial differential equations modelling the problem are reduced to ordinary differential equations following the application of the similarity transformations. The system has been solved analytically with the differential transform method and numerically with the Runge–Kutta–Fehlberg 4th–5th order method with the assistance of the shooting technique. Comprehensive analysis and discussion have been conducted regarding the impact of multiple governing parameters on the dimensionless velocity and temperature distributions. These parameters include variable thermal conductivity, nonlinear thermal radiation, Hartman number, and hybrid nanoparticle volume fraction. Finally, this method will provide some insights into the usefulness of MHD hybrid nanofluid flow in convergent-divergent channels, and the results produced by the analytical data have also been strengthened and verified by the use of numerical data as well as data from the literature.

Lipid core-chitosan shell hybrid nanoparticles for enhanced oral bioavailability of sorafenib.

Limited aqueous solubility is a major hurdle resulting in poor and variable oral bioavailability, high doses, side effects, and the suboptimal therapeutic efficacy of sorafenib (SRF). In this study, we developed SRF-loaded solid lipid nanoparticles (SRF-SLNs) and lipid core-chitosan shell hybrid nanoparticles (CS-SRF-SLNs) to improve the oral absorption of SRF. SRF-SLNs were prepared using a stearyl alcohol core stabilized with a surfactant mixture, followed by surface decoration with chitosan to form CS-SRF-SLNs. The developed SRF-SLNs and CS-SRF-SLNs displayed uniform and well-separated spherical particles with small particle size (112.2 and 124.6 nm), low PDI (0.114 and 0.148), adequate zeta potential (-18.6 and +21.2 mV) and high encapsulation efficiency (92.0 and 91 %). Thermal and crystallinity studies (DSC and PXRD) confirmed the successful incorporation of SRF into the lipid matrix and its conversion to the amorphous state. The CS-SRF-SLNs demonstrated sustained SRF release in simulated gastric and intestinal fluids with improved aqueous solubility. Following oral administration to rats, CS-SRF-SLNs significantly improved SRF bioavailability compared with SRF-SLNs and SRF dispersion. Collectively, CS-SRF-SLNs were found to be superior to SRF-SLNs owing to their better sustained-release profile and pharmacokinetic parameters, thereby demonstrating their usefulness for oral delivery by minimizing the solubility-related issues of SRF.

Barcoded Hybrids of Extracellular Vesicles and Lipid Nanoparticles for Multiplexed Analysis of Tissue Distribution.

Targeted delivery of therapeutic agents is a persistent challenge in modern medicine. Recent efforts in this area have highlighted the utility of extracellular vesicles (EVs) as drug carriers, given that they naturally occur in bloodstream and tissues, and can be loaded with a wide range of therapeutic molecules. However, biodistribution and tissue tropism of EVs remain difficult to study systematically.Here, a multiplexed approach is developed for simultaneous tracking of EVs from various cell lines within a single in vivo experiment. EVs are used from 16 different cell lines, and through controlled fusion with lipid nanoparticles (LNPs) carrying single-stranded DNA barcodes, uniquely barcoded hybrid EV particle (hEV) library is generated. These hEVs are combined for a multiplexed in vivo biodistribution profiling in mice, and discovered that HAP1-derived hEVs demonstrated lung tropism, suggesting that these hEVs may be used for targeted drug delivery into lung tissue. To examine this possibility further, it is shown that HAP1 hEV loaded with Cre mRNA displayed functional delivery to the lungs. Overall, the barcoded hEV technology enables rapid profiling of biodistribution across EV cell sources, which is poised to improve throughput and extent of EV studies, while reducing the number of animals required for research.