Nanoprecipitation Method Research Articles

Nanoparticles modified with glucose analogs to enhance the permeability of the blood-brain barrier and their accumulation in the epileptic brain.

Drug delivery for epilepsy treatment faces enormous challenges, where the sole focus on enhancing the ability of drugs to penetrate the blood-brain barrier (BBB) through ligand modification is insufficient because of the absence of seizure-specific drug accumulation. In this study, an amphipathic drug carrier with a glucose transporter (GLUT)-targeting capability was synthesised by conjugating 2-deoxy-2-amino-D-glucose (2-DG) to the model carrier DSPE-PEG2k. A 2-DG-modified nano drug delivery system (NDDS) possessing robust stability and favourable biocompatibility was then fabricated using the nanoprecipitation method. The results showed that the 2-DG-modified NDDS exhibited enhanced cellular uptake by brain capillary endothelial cells and neuronal cells. Most importantly, the 2-DG-modified NDDS exhibited enhanced BBB penetration and brain accumulation, especially in the epileptic brain, thus achieving seizure-based on-demand drug delivery. Our study provides a simple and smart strategy for the delivery of anti-seizure medicines.

Polyfluorene-Enhanced Near-Infrared Electrochemiluminescence of Heptamethine Cyanine Dye for Coreactants-Free Bioanalysis.

The near-infrared electrochemiluminescence (NIR-ECL) technique has received special attention in cell imaging and biomedical analysis due to its deep tissue penetration, low background interference, and high sensitivity. Although cyanine-based dyes are promising NIR-ECL luminophores, limited ECL efficiency and the need for exogenous coreactants have prevented their widespread application. In this work, poly[9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene]-alt-2,7-(9,9-dioctylfluorene)] (PFN) was innovatively developed to significantly invigorate the NIR-ECL performance of heptamethine cyanine dye IR 783 by the resonance energy transfer (RET) strategy. Astonishingly, the IR@PFN nanoparticles (NPs) synthesized from IR 783 and PFN by a nanoprecipitation method emitted a strong coreactant-free NIR-ECL signal at +1.05 V, and the maximum emission wavelength was 815 nm. IR@PFN NPs were integrated in a spontaneous entropy-driven chain replacement (ESDR) reaction to achieve ECL analysis of microRNA-21 (miRNA-21), and the limit of detection was as low as 0.25 fM. IR@PFN NPs created a promising coreactant-free NIR-ECL platform for bioanalysis and imaging, providing a novel NIR-ECL detection method for miRNA-21.

Preparation and physicochemical properties of OSA modified Cyperus esculentus starch nanoparticles.

The aim of this study was to investigate the Octenyl succinic anhydride (OSA) modification and nanonization of Cyperus esculentus starch (CES) on its physicochemical properties. Cyperus esculentus starch nanoparticles (SNPs) were prepared by nanoprecipitation method and modified with OSA. The results showed that the average particle size of the prepared SNPs was 125.25nm, and the OSA modified nanoparticles (OS-SNPs) were between 411.16 and 442.07nm. Chemical group analysis indicated the successful esterification reaction of OSA. Crystallographic structure analysis showed that the crystalline type of CES remained unchanged after OSA modification, but the crystallinity was slightly decreased. Moreover, SNPs exhibited a V-type diffraction peak. Morphological observation results showed that the hydrophobic groups introduced after OSA modification of SNPs had caused particle deformation and formed a network structure. In addition, the gelatinization temperature of starch decreased after OSA modification, and the gelatinization temperature could no longer be measured after nanonization. The OSA modified CES (OS-CES) had shown higher viscosity, swelling power and solubility during the gelatinization process. While the nanonized samples had no obvious viscosity change during the heating process, the solubility remained at a relatively high level of 70-90%.

Continuous Production of Docetaxel-Loaded Nanostructured Lipid Carriers Using a Coaxial Turbulent Jet Mixer with Heating System.

The continuous synthesis of nanoparticles (NPs) has been actively studied due to its great potential to produce NPs with reproducible and controllable physicochemical properties. Here, we achieved the high throughput production of nanostructured lipid carriers (NLCs) using a coaxial turbulent jet mixer with an added heating system. This device, designed for the crossflow of precursor solution and non-solvent, combined with the heating system, efficiently dissolves solid lipids and surfactants. We reported the flow regime according to the Reynolds number (Re). Also, we confirmed the size controllability of NLCs as dependent on both Re and lipid concentration. The optimized synthesis yields NLCs around 80 nm, ideal for targeted drug delivery by enhanced permeability and retention (EPR) effect. The coaxial turbulent jet mixer enables effective mixing, producing uniform size distribution of NLCs. The NLCs prepared using the coaxial turbulent jet mixer were smaller, more uniform, and had higher drug loading compared to the NLCs synthesized by a bulk nanoprecipitation method, showcasing its potential for advancing nanomedicine.

Engineering of redox-triggered polymeric lipid hybrid nanocarriers for selective drug delivery to cancer cells.

Tunable redox-sensitive polymeric-lipid hybrid nanocarriers (RS-PLHNCs) were fabricated using homogenization and nanoprecipitation methods. These nanocarriers were composed of novel redox-cholesterol with disulfide linkages and synthesized by conjugating cholesterol with dithiodipropionic acid via esterification. Berberine (BBR) was loaded into the fabricated nanocarriers to investigate the selective uptake of BBR by cancer cells as well as its release and enhanced cytotoxicity. The optimized BBR nanocarriers BBR NP-17 and -18 exhibited a spherical shape and uniform distribution, with a particle size of 124.7 ± 1.2 nm and 185.2 ± 1.6 nm and a zeta potential of -5.9 ± 2.5 mV and -20.3 ± 1.1 mV, respectively. These NCs released >80% BBR in a simulated intracellular tumor microenvironment (TME), while only 30%-45% was released under normal physiological conditions. The accelerated drug release in the TME was due to disulfide bond cleavage and ester bond hydrolysis in the presence of GSH and acidic pH, whereas under normal conditions, the NCs remained stable/undissociated. Cellular uptake studies confirmed enhanced BBR uptake in GSH-rich cancer cells (H1975) compared with normal cells (BEAS-2B and HEK293A). Following uptake, compared with the free form of the drug, the optimized nanocarriers displayed significant selective cytotoxicity and apoptosis in cancer cells by notably downregulating anti-oxidant (NFE2L2, HO-1, NQO1, and TXRND1) and anti-apoptotic (MCL-1) genes while upregulating pro-apoptotic genes (PUMA and NOXA). This resulted in increased oxidative stress, thereby inducing selective apoptosis in the GSH-rich lung cancer cells. These results suggest that the synthesized novel NCs hold great potential for specifically delivering drugs to cancer cells (with a reduced environment) while sparing normal cells, thus ensuring safe and efficient cancer therapy.

A general strategy towards activatable nanophotosensitizer for phototoxicity-free photodynamic therapy.

Background: Photodynamic therapy (PDT) has gained widespread attention in cancer treatment, but it still faces clinical problems such as skin phototoxicity. Activatable photosensitizers offer a promising approach to addressing this issue. However, several significant hurdles need to be overcome, including developing effective activation strategies and achieving the optimal balance between photodynamic effects and related side effects. Herein, we present a novel and general strategy for the construction of tumor-targeted activatable nanophotosensitizers (TNP1/PSs). Methods: TNP1/PSs were constructed through simple nanoprecipitation method, leveraging the strong cation-π interaction between cationic polymers and aromatic photosensitizers. We conducted a comprehensive characterization and investigation of the photoactivity, as well as the mechanisms underlying both OFF state and switched-on properties of TNP1/PSs. Additionally, we thoroughly evaluated the cytotoxicity, tumor-targeted ability, and anti-tumor efficacy of TNP1/PSs in the 4T1 cell line. Results: TNP1/PSs exhibit a markedly fully OFF state of photoactivity, subsequent to self-assembly through cation-π interactions in aqueous media. The mechanism study reveals a multi-pathway process induced by cation-π complexes, which includes reduced absorption and radiative decay, as well as enhanced thermal decay and intermolecular charge transfer. Upon targeting tumor cells, TNP1/PSs were effectively endocytosed and predominantly traversed the lysosomes, where degradation of the cationic polymer occurs, resulting in the spontaneous switch-on of PDT activity. In vivo studies employing small animal models demonstrated that the as-synthesized nanophotosensitizer possesses remarkable anti-tumor activity while completely avoiding skin phototoxicity. Conclusion: This work provides a powerful platform for efficiently constructing tumor-targeted activatable nanophotosensitizers, paving the way for safe and effective photodynamic therapy in cancer treatment.

Targeted Nanotherapy by Vinblastine-Loaded Chitosan-Coated PLA Nanoparticles to Improve the Chemotherapy via Reactive Oxygen Species to Hamper Hepatocellular Carcinoma.

Liver cancer is a prevalent and significant cause of death in humans. The use of novel biodegradable materials for various biomedical applications is being recently recommended as complementary as well as alternative solution for traditional chemotherapy. This study focuses on the synthesis of biodegradable nanocarriers [chitosan-coated poly(lactic acid) NPs (Cht-PLA NPs)] for the delivery of an anticancer drug vinblastine (Vbx) and to evaluate its therapeutic potential in human hepatocellular carcinoma (HepG2) cells. The Cht-PLA NPs were synthesized using the nanoprecipitation method and characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential techniques. The results showed that the nanoparticle sizes are in the range of 100-200 nm with positive surface charge. The release profile of the synthesized nanoformulation showed controlled release of the Vbx drug for 72 h. The anticancer efficacy of the synthesized nanoformulation was assessed on the HepG2 cell lines. The in vitro cytotoxicity study revealed that the Vbx-loaded Cht-PLA NPs showed higher toxicity with an increase in concentration as compared to the Vbx alone. Additionally, an in vitro cellular uptake study revealed higher internalization as compared to the drug alone due to the chitosan coating. Further, the ability to stimulate the reactive oxygen species (ROS) generation and variation in mitochondrial membrane potential at the IC50 concentration of Vbx-loaded Cht-PLA NPs was confirmed by using 2,7-dichlorodihydrofluorescein diacetate and rhodamine 123 dyes, respectively, and were analyzed under fluorescence microscopy. Hence, the results showed that Vbx-loaded Cht-PLA NPs possess high anticancer activity due to its higher cellular toxicity, cellular uptake, increased ROS production, and disruption in mitochondrial membrane potential. All these properties of the synthesized nanoformulation suggest it's potential applications in drug delivery systems, targeting liver cancer.

Formulation and Characterization of Resveratrol-Loaded Nanostructured Lipid Carriers (NLC) with Mesua ferrea Seed Oil as Liquid Lipid

Nanostructured Lipid Carriers (NLCs) are colloidal drug delivery systems composed of both solid and liquid lipids. They enhance drug loading capacity, regulate the release of poorly water-soluble drugs, and are suitable for targeted delivery. Resveratrol, a polyphenol with promising anticancer properties, faces challenges due to its low water solubility, poor bioavailability, and chemical instability, resulting in rapid metabolism and excretion. Therefore, it is crucial to develop a delivery system that safeguards resveratrol during its transit through the body. This study aimed to develop and characterize resveratrol-loaded NLCs using the nano-precipitation method followed by ultrasonication, incorporating Mesua ferrea seed oil as the liquid lipid. The NLCs were evaluated for particle size, morphology (TEM), zeta potential, drug entrapment efficiency, drug loading, and in vitro drug release. The resulting NLCs demonstrated stability and homogeneity, with a particle size of 181.6 ± 12.4 nm, a polydispersity index (PDI) of 0.135 ± 0.09, drug entrapment efficiency of 82.76 ± 12.2%, and drug loading capacity of 42.94 ± 7.5%. They exhibited sustained drug release, achieving 84.56% release within 24 h. These findings suggest that the developed NLCs can effectively enhance the incorporation and controlled release of poorly water-soluble drugs like resveratrol, offering potential advantages over conventional delivery systems.

Efficient Quasi-Homogenous Photocatalysis Enabled by Molecular Nanophotocatalysts with Donor-Acceptor Motif.

Polymer semiconductors have attracted much attention for photocatalytic hydrogen evolution, but they typically exhibit micrometer-sized particles in water-suspension, causing severe loss in light absorption and exciton recombination. Here a molecular nanophotocatalyst featuring a donor-acceptor motif is presented that solution is processed via a facile stirring nanoprecipitation method assisted by hydrophilic surfactants, enabling an efficient quasi-homogenous hydrogen evolution. In contrast to the original bulk powder (heterogeneous system), these quasi-homogenous nanophotocatalysts exhibit significantly improved light-harvesting, water-wettability, and exciton dissociation, resulting in distinctly enhanced (by four-order-of-magnitude) photocatalytic hydrogen evolution rate. The optimized nanophotocatalysts (4CzPN/DDBAB/SDBS) generate an outstanding hydrogen evolution rateof 116.42mmolg-1h-1 and apparent quantum yield of 30.2% at 365nm, which are among the highest reported for single-junction organic photocatalysts. The scalability of the quasi-homogenous photocatalysts is further demonstrated using a flow-based flash nanoprecipitation (FNP) processing.

Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes.

Disulfiram (DSF) reduces insulin resistance and weight gain in obese mice. However, the effect on adipose tissue is unexplored due to their high instability under physiological conditions, limiting clinical applications. Thus, it is meaningful to develop a DSF carrier for sustained release to adipose tissue. We optimized the synthesis of poly-ε-caprolactone (PCL) nanoparticles (NPs) loaded with DSF and analyzed their effect on adipose tissue cells in vitro. The NPs were synthesized by nanoprecipitation method, varying its solvent, either acetone or acetone/dichloromethane (60:40) (v/v), and ratio PCL:DSF (w/w) 1:2, 1:1, 2:1 and, 1:0; finding the best condition was obtained with acetone/dichloromethane solvent mixture and 2:1 PCL:DSF. Then, NPs toxicity was analyzed on adipose cells (preadipocytes, white-like adipocytes, and macrophages) assessing association and internalization, cell viability, and cell death mechanism. NPs were spherical with a particle size distribution of 203.2 ± 29.33 nm, a ζ-potential of -20.7 ± 4.58 mV, a PDI of 0.296 ± 0.084, and a physical drug loading of 18.6 ± 5.80%. Sustained release was observed from 0.5 h (10.94 ± 2.38%) up to 96h (91.20 ± 6.03%) under physiological conditions. NPs internalize into macrophages, white-like adipocytes and preadipocytes without modifying cell viability on white-like adipocytes and macrophages. Preadipocytes reduce cell viability, inducing mitochondrial damage, increased mitochondrial reactive oxygen species production and loss of mitochondrial membrane potential, leading to effector caspases 3/7 cleaved, resulting in apoptosis. Finally, long-term proliferation inhibition was observed, highlighting the bioequivalent effect of PCL-DSF NPs compared to free DSF. Our data demonstrated the biological interaction of PCL NPs with adipose cells in vitro. The selective cytotoxicity of DSF towards preadipocytes resulted in milder effects when it was delivered nanoencapsulated compared to the free drug. These results suggest promising pharmacological alternatives for DSF long-term delivery on adipose tissue.

Dexamethasone Acetate-Loaded PLGA Nanospheres Targeting Liver Macrophages.

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300nm are prepared, achieving a DA-loading efficiency of 19%. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

Electrostatic Gelatin Nanoparticles for Biotherapeutic Delivery.

Biological agents such as extracellular vesicles (EVs) and growth factors, when administered in vivo, often face rapid clearance, limiting their therapeutic potential. To address this challenge and enhance their efficacy, we propose the electrostatic conjugation and sequestration of these agents into gelatin-based biomaterials. In this study, gelatin nanoparticles (GNPs) were synthesized via the nanoprecipitation method, with adjustments to the pH of the gelatin solution (4.0 or 10.0) to introduce either a positive or negative charge to the nanoparticles. The GNPs were characterized using dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM) imaging. Both positively and negatively charged GNPs were confirmed to be endotoxin-free and non-cytotoxic. Mesenchymal stem cell (MSC)-derived EVs exhibited characteristic surface markers and a notable negative charge. Zeta potential measurements validated the electrostatic conjugation of MSC-EVs with positively charged GNPs. Utilizing a transwell culture system, we evaluated the impact of EV-GNP conjugates encapsulated within a gelatin hydrogel on macrophage secretory activity. The results demonstrated the bioactivity of EV-GNP conjugates and their synergistic effect on macrophage secretome over five days of culture. In summary, these findings demonstrate the efficacy of electrostatically coupled biotherapeutics with biomaterials for tissue regeneration applications.

Aceclofenac delivery through polymeric nanoparticles loaded with transdermal hydrogel against rheumatoid arthritis

Hydrogels have gained attention in drug delivery systems for their ability to encapsulate nanoparticles, providing sustained and targeted release. In this study, polymeric nanoparticles (NPs) of aceclofenac (ACE) were loaded into a carbopol-based hydrogel to overcome problems associated with the conventional treatment concerning rheumatoid arthritis (RA). Polymeric NPs of ACE were fabricated via the nanoprecipitation method and incorporated into a Carbopol 934-based hydrogel with a permeation enhancer (PE). Furthermore, ACE-NPs was characterized and subjected to in vitro and ex vivo analyses, which revealed a sustained release (20 % drug release at pH 5.5 and 40 % release at pH 7.4) and the desired permeation flux (1200 μg/cm2) of the ACE-NP-loaded hydrogel with PE after 24 h. The optimized nanoparticles had a particle size of 141.1 nm and an entrapment efficiency (EE) of 87 %. XRD and FTIR further supported the structural and compositional analysis of the ACE-NPs. The physicochemical properties of the ACE-NPs loaded hydrogel with PE were also characterized. An in vivo study was carried out on a CFA-induced RA mice model. The behavioral parameters were investigated, and supportive histopathological and radiological data were recorded. These findings suggest that ACE-NPs loaded hydrogel is a promising treatment for RA.

In silico and in vivo evaluations of fisetin and fisetin-loaded nanosuspension on monoamine oxidase inhibition in Aβ(25–35) induced dementia in mice model

BackgroundAmyloid beta (Aβ) plaques on the extracellular matrix and intracellular neurofibrillary tangles comprise the key indicative pathology of Alzheimer's disease (AD). Fisetin, an antioxidant bioactive compound having pharmacotherapeutic effects is applied by traditional Chinese medicine (TCM) such as Toxicodendron vernicifum (Chinese lacquer tree), Cotinus coggygria Scop, Gan Shuang granulates and formula of Acacia catechu-Scutellariae Radix. Nevertheless, fisetin has constraints such as low oral bioavailability, insignificant aqueous solubility and high hepatic metabolisms. ObjectiveThis investigation aimed to envisage the effects of fisetin and its optimised nanoformulation on Aβ(25–35) desirous neurotoxicity in mice through deciphering inhibitory actions against monoamine oxidase A and B (MAO-A and B) enzymes following molecular docking. MethodsMolecular docking with MAO-A and B enzymes were accomplished by AMDock's integrated AutoDock Tools (ADT) scripts. For in vivo studies, fisetin nanosuspension was prepared by nanoprecipitation method and evaluated for standard characterization. 10 and 20 mg/kg of fisetin and 10 mg/kg of fisetin nanosuspension were given once daily to mice for 21 days. On the 15th day, the mice were challenged with Aβ(25–35) by intracerebroventricular injection (ICV) and behavioural tests (open field and elevated plus maze) were performed on the 20th day. Biochemical and histology were examined in brain tissues. ResultsFisetin docked to the catalytic positions of MAO-A and B, unveiling good binding scores and molecular interactions with amino acid residues for inhibition activities. Fisetin nanosuspension has average particle size (225.4 ± 2.95 nm) with low polydispersity index (0.19) and standard zeta potential (-19.13 ± 1.17 mV). Findings showed that fisetin increased locomotor activity and reduced anxiety-like behaviour. Fisetin and its nanosuspension significantly reduced the concentration of MAO-A (P < 0.01) and MAO-B enzymes suggesting a potential neuroprotection effect in Aβ peptide-induced amnesia in mice. ConclusionFisetin with optimized bioavailability, effectively exhibits neuroprotection through molecular interactions of MAO enzymes. Further investigations affidavits the neuroprotection through bidirectional pathways related to biogenic amines and their deamination on Aβ stress conditions.

SYNERGISTIC EFFECT LUNG CANCER THERAPY: CO-DELIVERY OF QUERCETIN AND CISPLATIN VIA EUDRAGIT L-100 NANOPARTICLES IN VITRO

Objective: This study aims to investigate the potential of Eudragit L-100 nanoparticles for the co-delivery of quercetin and cisplatin to lung cancer cells, seeking to exploit the synergistic effects of the two drugs while overcoming their individual limitations. Methods: We investigate the synergistic effect of co-delivering quercetin and cisplatin using Eudragit L-100 nanoparticles for lung cancer therapy. The nanoparticles were synthesized using the nanoprecipitation method, where Eudragit L-100 was dissolved in an organic solvent, followed by the incorporation of quercetin and cisplatin. The resultant nanoparticles were characterized for size, zeta potential, drug loading efficiency, and morphology using techniques such as Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Results: The co-loaded Quercetin-Cisplatin Nanoparticles (Qu-Cis)-NPs formulation had a mean particle size of 475±4.77 nm. Polydispersion index of 0.266±0.093 and zeta potential was-24.03±0.89 mV. The in vitro cytotoxicity was assessed using normal cell and lung cancer cell lines in vitro studies showed that the developed nanoparticles significantly increased cancer cell mortality compared to individual drug treatments. The combination (Qu-Cis)-NPs showed more cytotoxicity on the Non-Small Lung Cancer Cell Line (NCI-H460) cancer cell line after 48 h of incubation compared to Qu loaded-NPs and Cis loaded-NPs, particularly at a concentration of 1 mg/ml. The combination showed no cytotoxicity effect on normal Human Lung fibroblast cell Lines (CCD-19 lu) cells at all concentrations after 24 h, but showed cytotoxicity effects at concentrations (0.125, 0.25, 0.5, and 1.0) mg/ml after 48 h. Conclusion: The Eudragit L-100 nanoparticle system for co-delivering quercetin and cisplatin showed a promising synergistic effect in lung cancer treatment. It effectively addresses the solubility and toxicity issues of both drugs, offering a potentially more effective treatment option that merits further clinical investigation.

Colon-targeted self-assembled nanoparticles loaded with berberine double salt ameliorate ulcerative colitis by improving intestinal mucosal barrier and gut microbiota

Ulcerative colitis (UC) is a chronic, recurrent inflammatory bowel disease marked by disturbances in intestinal mucosal barriers, persistent inflammation, oxidative stress, and dysbiosis of the intestinal microbiota. Traditional treatments often fail to adequately address these issues, primarily targeting inflammation. To address these limitations, this study developed an innovative approach using self-assembled nanoparticles for oral administration that target colonic inflammation. Berberine hydrochloride and ursodeoxycholic acid were combined to form a double salt (BeU), enhancing solubility and encapsulation. An amphiphilic polymer (FU-PA) was created by esterifying fucoidan with palmitic acid. FU-PA/BeU nanoparticles were prepared using the nanoprecipitation method and further encapsulated in acid-resistant sodium alginate microspheres (FU-PA/BeU NPs@MS) for targeted delivery to colonic lesions. The aggregation rate of nanoparticles with mucus was significantly reduced to 59 % of free berberine, while the apparent permeability coefficient increased by 2.4 times. In vitro, FU-PA/BeU NPs effectively targeted inflammatory macrophages, reducing IL-6 and NO levels while increasing IL-10 level (to 42.5 %, 26.8 %, and 539 % of the LPS-treated group, respectively). Additionally, the ABTS and DPPH radical scavenging capabilities of FU-PA/BeU NPs were 177.8 % and 151.7 % of BeU, respectively. In dextran sulphate sodium-induced UC mice, oral FU-PA/BeU NPs@MS significantly improved epithelial and mucosal barriers, restored gut microbiota diversity, reduced inflammation and oxidative stress. Remarkably, the mean colon length in the FU-PA/BeU NPs@MS group was 1.2 times longer than that in the sulfasalazine group. These dual-targeted FU-PA/BeU NPs@MS show great potential for UC treatment.

Preparation of Disulfide/Trisulfide Core-Cross-Linked Polycarbonate Nanocarriers for Intracellular Reduction-Triggered Drug Release.

Polymeric nanocarriers have attracted significant attention in the field of anticancer drug delivery due to their unique advantages. However, designing nanocarriers that can maintain stability in the bloodstream while achieving specific drug release within tumor cells remains a major challenge. To address this issue, constructing reversible cross-linked polymeric nanocarriers that are sensitive to the intracellular reducible glutathione (GSH) characteristic of the tumor microenvironment is a promising strategy. Based on this, we designed and synthesized two novel six-membered bicyclic carbonate monomers containing disulfide (DSBC) and trisulfide (TSBC) bonds. Through a one-step ring-opening polymerization, a series of reduction-sensitive polycarbonate copolymers (i.e., PEG-PDSBC and PEG-PTSBC) were prepared, and doxorubicin (DOX)-loaded nanoparticles were fabricated using a nanoprecipitation method. The in vitro drug release behaviors of these nanoparticles were systematically investigated. The results showed that these polymers, due to the cross-linked structure formed by the ring-opening polymerization of their bicyclic monomers, could self-assemble into stable nanoparticles. Under different concentrations of glutathione, DOX-loaded PEG-PTSBC nanoparticles demonstrated faster drug release, indicating more optimized intracellular drug release properties. Further cytotoxicity experiments revealed that both types of blank nanoparticles exhibited good biocompatibility with the 4T1 and NIH-3T3 cells. Fluorescence microscopy and flow cytometry results further indicated that DOX-loaded PEG-PTSBC nanoparticles released more drugs in 4T1 cells, significantly inhibiting tumor cell growth compared with DOX-loaded PEG-PDSBC nanoparticles, with no noticeable difference in NIH-3T3 normal cells. In conclusion, this study suggests that trisulfide cross-linked polycarbonate-based nanocarriers hold promise as an anticancer drug delivery system that combines stability in the bloodstream with specific intracellular drug release, offering new insights for the development of novel, efficient, and safe anticancer nanomedicines.

Maltodextrin-derived nanoparticles resensitize intracellular dormant Staphylococcus aureus to rifampicin

Intracellular bacteria are recognized as a crucial factor in the persistence and recurrence of infections. The efficacy of current antibiotic treatments faces substantial challenges due to the dormant state formation of intracellular bacteria. In this study, we devised a strategy aimed at reverting intracellular dormant bacteria to a metabolically active state, thereby increasing their vulnerability to antibiotics. We found that oligosaccharides, especially maltodextrin (MD), can be absorbed by dormant S. aureus, leading to their revival and restoration of sensitivity to rifampicin (Rif). We then synthesized a reactive oxygen species (ROS)-responsive MD-prodrug by covalently binding MD with 4-(hydroxymethyl) phenylboronic acid pinacol ester (MD-PBAP) and prepared a ROS-responsive nanoparticles (MDNP) using a nanoprecipitation and self-assembly method. Once internalized by host cells, MDNP was degraded to MD, reactivating dormant S. aureus, and enhancing their susceptibility to Rif. More importantly, MDNP treatment restored the sensitivity of intracellular persistent S. aureus to Rif in both a reservoir transfer model and whole-body infection model. Additionally, MDNP have demonstrated excellent biocompatibility in both in vitro and in vivo settings. These results offer a promising therapeutic avenue for managing persistent intracellular bacterial infections by reviving and resensitizing intracellular dormant bacteria to conventional antibiotics.

Synergistic Enhancement of Carboplatin Efficacy through pH-Sensitive Nanoparticles Formulated Using Naturally Derived Boswellia Extract for Colorectal Cancer Therapy.

Carboplatin (Cp) is a potent chemotherapeutic agent, but its effectiveness is constrained by its associated side effects. Frankincense, an oleo-gum resin from the Boswellia sacra tree, has demonstrated cytotoxic activity against cancer cells. This study explored the synergistic potential of nanoparticles formulated from Boswellia sacra methanolic extract (BME), to enhance the therapeutic efficacy of Cp at reduced doses. Nanoparticles were prepared via the nanoprecipitation method, loaded with Cp, and coated with positively charged chitosan (CS) for enhanced cell interaction, yielding Cp@CS/BME NPs with an average size of 160.2 ± 4.6 nm and a zeta potential of 12.7 ± 1.5 mV. In vitro release studies revealed a pH-sensitive release profile, with higher release rates at pH 5.4 than at pH 7.4, highlighting the potential for targeted drug delivery in acidic tumor environments. In vitro studies on HT-29 and Caco-2 colorectal cancer cell lines demonstrated the nanoformulation's ability to significantly increase Cp uptake and cytotoxic activity. Apoptosis assays further confirmed increased induction of cell death with Cp@CS/BME NPs. Cell-cycle analysis revealed that treatment with Cp@CS/BME NPs led to a significant increase in the sub-G1 phase, indicative of enhanced apoptosis, and a marked decrease in the G1-phase population coupled with an increased G2/M-phase arrest in both cell lines. Further gene expression analysis demonstrated a substantial downregulation of the anti-apoptotic gene Bcl-2 and an upregulation of the pro-apoptotic genes Bax, PUMA, and BID following treatment with Cp@CS/BME NPs. Thus, this study presents a promising and innovative strategy for enhancing the therapeutic efficacy of chemotherapeutic agents using naturally derived ingredients while limiting the side effects.

Optimisation of the carvacrol encapsulation method into PHBV nanoparticles

The need of sustainable food packaging preserving food from degradation conducted to increase research on active packaging using essential oil, as carvacrol, for their antimicrobial and antioxidant properties. The encapsulation of this kind of volatile molecules is necessary and nanoencapsulation into biopolymers, as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) showed an increasing interest as a green solution, although this method again need to be improved. In this study, a full experimental design was developed to select the best method (nanoprecipitation and emulsification) and operating conditions (PHBV molecular weight, surfactant concentration, carvacrol/PHBV ratio and Aqueous/Organic phase volume ratios) to encapsulate carvacrol into PHBV. In this purpose, for each tested conditions, encapsulation efficiency (process efficiency, carvacrol recovery, PHBV recovery and loading capacity), as well as nanoparticles’ morphology and size were estimated, and statistically analysed. Carvacrol recovery and loading capacity were significatively highest (61 % and 100 % respectively) using emuslification method, low surfactant concentration, high carvacrol/PHBV ratio (for loading capacity) and low PHBV molecular weight (for carvacrol recovery). To the contrary, PHBV recovery increased (93 %) using the nanoprecipitation method, a high surfactant concentration and a low carvacrol/PHBV ratio, while process efficiency increased (73 %) with a low carvacrol/PHBV ratio and a low aqueous/organic phase volume ratio. Moreover, small spherical-shaped and separated nanoparticles were obtained using emulsification method, high surfactant concentration but low carvacrol/PHBV ratio. Therefore, including all the aspects of carvacrol nanoencapsulation into PHBV (shape and encapsulation efficiency) using emulsification method, with a low level for all parameters except the surfactant concentration are the most suitable strategy.