Topical Application of Dexamethasone-Loaded Core-Multishell Nanocarriers Against Oral Mucosal Inflammation.

Topical treatment of oral inflammatory diseases is challenging due to the intrinsic physicochemical barriers of the mucosa and the continuous flow of saliva, which dilute drugs and limit their bioavailability. Nanocarrier technology can be an innovative approach to circumvent these problems and thus improve the efficacy of topical drug delivery to the mucosa. Core-multishell (CMS) nanocarriers are putative delivery systems with high biocompatibility and the ability to adhere to and penetrate the oral mucosa. Ester-based CMS nanocarriers release the anti-inflammatory compound dexamethasone (Dx) more efficiently than a conventional cream. Mussel-inspired functionalization of a CMS nanocarrier with catechol further improves the adhesion of the nanocarrier and may enhance the efficacy of the loaded drugs. In the present study, the properties of the ester-based CMS 10-E-15-350 nanocarrier (CMS-NC) are further evaluated in comparison to the catechol-functionalized variant (CMS-C0.08). While the mucoadhesion of CMS-NC is inhibited by saliva, CMS-C0.08 exhibits better mucoadhesion in the presence of saliva. Due to the improved adhesion properties, CMS-C0.08 loaded with dexamethasone (Dx-CMS-C0.08) shows a better anti-inflammatory effect than Dx-CMS-NC when applied dynamically. These results highlight the superiority of CMS-C0.08 over CMS-NC as an innovative drug delivery system (DDS) for the treatment of oral mucosal diseases.

Intestinal distribution of anionic, cationic, and neutral polymer-stabilized nanocarriers measured with a lanthanide (europium) tracer assay.

Nanocarriers, more commonly called nanoparticles (NPs), have found increasing use as delivery vehicles which increase the oral bioavailability of poorly water-soluble and peptide therapeutics. Therapeutic bioavailability is commonly assessed by measuring plasma concentrations that reflect the absorption kinetics. This bioavailability is a convolution of the gastrointestinal distribution of the NP vehicle, the release rate of the encapsulated therapeutic cargo, and the absorption-metabolism-distribution kinetics of the released therapeutic. The spatiotemporal distribution of the NP vehicle in the gastrointestinal tract is not well studied and is a buried parameter in PK studies used to measure the effectiveness of an NP formulation. This work is a study of the intestinal distribution and fate of orally dosed NPs in male CD-1 mice over 24 h. NPs have identical hydrophobic cores - composed of poly(styrene) homopolymer, a naphthalocyanine dye, and oleate-coated europium oxide colloids - with one of four different surface stabilizers: neutral poly(styrene)-block-poly(ethylene glycol) (PS-b-PEG), moderately negative hydroxypropyl methylcellulose acetate succinate (HPMCAS), highly negative poly(styrene)-block-poly(acrylic acid) (PS-b-PAA), and highly cationic adsorbed chitosan HCl on PS-b-PAA stabilized NPs. NP hydrodynamic diameters are all below 200 nm, with some variation attributable to the molecular properties of the stabilizing polymer. The encapsulated hydrophobic europium oxide colloids do not release soluble europium ions, enabling the use of highly sensitive inductively coupled plasma mass spectrometry (ICP-MS) to detect NP concentrations in digested biological tissues. Highly anionically-charged PAA and cationically-charged chitosan stabilized NPs showed statistically significant increased retention compared to the neutral PEG-stabilized NPs at p < 0.05 significance and (1-ß) > 0.95 power. HPMCAS-stabilized NPs showed statistically insignificant greater retention than PEG-stabilized NPs, and all NP formulations showed clearance from the intestines within 24 h. Different surface charges preferentially reside in different segments of the intestines, where cationic chitosan-stabilized NPs showed increased retention in the small intestines (ileum) and anionic PAA-stabilized NPs in the large intestines (caecum and colon). Modifying the surface charge of a NP can be used to modulate mucoadhesion, total retention, and intestinal segment specific retention, which enables the rational design of delivery vehicles that maximize residence times in appropriate locations.

Characterization of CYP303A1 and its potential application based on ZIF-8 nanoparticle-wrapped dsRNA in Nilaparvata lugens (Stål).

BACKGROUND: RNA interference (RNAi) technology has been put forward as a promising method for pest control and resistance management. Mining highly efficient lethal genes and constructing stable double-stranded RNA (dsRNA) delivery systems are of great significance to improve the application potential of RNAi technology. RESULTS: In this study, we characterized a molting-related gene, NlCYP303A1, in Nilaparvata lugens that was highly expressed in the cuticle and at the end stages of each instar in nymphs. Silencing the expression of NlCYP303A1 in N. lugens resulted in a deformed phenotype and a significant increase in mortality. Furthermore, interfering with NlCYP303A1 changed the relative expression of key genes in the chitin synthesis and degradation pathway. Finally, we used the nanocarrier zeolitic imidazolate framework-8 (ZIF-8) to load dsNlCYP303A1, forming a complex denoted as dsNlCYP303A1@ZIF-8. The results of both feeding and rice-seedling dip experiments indicated that the expression of NlCYP303A1 was dramatically and persistently suppressed by the dsNlCYP303A1@ZIF-8 treatment, compared with treatment with dsNlCYP303A1, suggesting that ZIF-8 can enhance the interference efficiency as well as the stability of dsNlCYP303A1. CONCLUSIONS: Our results demonstrate that the lethal gene NlCYP303A1 can be employed as an excellent target for RNAi technology by loading onto a nano-delivery system, and provide new insights into the creation of innovative pest control approaches. © 2024 Society of Chemical Industry.

Stable Porous Organic Cage Nanocapsules for pH-Responsive Anticancer Drug Delivery for Precise Tumor Therapy.

The search for drug nanocarriers with stimuli-responsive properties and high payloads for targeted drug delivery and precision medicine is currently a focal point of biomedical research, but this endeavor still encounters various challenges. Herein, a porous organic cage (POC) is applied to paclitaxel (PTX) drug delivery for cancer therapy for the first time. Specifically, water-soluble, stable, and biocompatible POC-based nanocapsules (PTX@POC@RH40) with PTX encapsulation efficiency over 98% can be synthesized by simply grafting nonionic surfactant (Polyoxyl 40 hydrogenated castor oil, RH40) on the POC surface. These PTX@POC@RH40 nanocapsules demonstrate remarkable stability for more than a week without aggregation and exhibit pH-responsive behavior under acidic conditions (pH 5.5) and display sustained release behavior at both pH 7.4 and pH 5.5. Intravenous administration of PTX@POC@RH40 led to a 3.5-fold increase in PTX bioavailability compared with the free PTX group in rats. Moreover, in vivo mouse model experiments involving 4T1 subcutaneous breast cancer tumors revealed that PTX@POC@RH40 exhibited enhanced anticancer efficacy with minimal toxicity compared with free PTX. These findings underscore the potential of POCs as promising nanocarriers for stimuli-responsive drug delivery in therapeutic applications.

Therapeutic effects of DOX-loaded hydrogel MOF nanocarriers on triple negative breast cancer and derivative design via reinforcement learning.

Triple negative breast cancer (TNBC) is one of the most difficult of all types of breast cancer to treat. TNBC is characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The development of effective drugs can help to alleviate the suffering of patients. The novel nickel(II)-based coordination polymer (CP), [Ni2(HL)(O)(H2O)3·H2O] (1) (where H4L=[1,1':2',1''-triphenyl]-3,3'',4',5'-tetracarboxylic acid), was synthesized via solvothermal reaction in this study. The overall structure of CP1 was fully identified by SXRD, Fourier transform infrared spectroscopy and elemental analysis. Using advanced chemical synthesis, we developed Hyaluronic Acid/Carboxymethyl Chitosan-CP1@Doxorubicin (HA/CMCS-CP1@DOX), a nanocarrier system encapsulating doxorubicin (DOX), which was thoroughly characterized using Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and Thermogravimetric Analysis (TGA). These analyses confirmed the integration of doxorubicin and provided data on the nanocarriers' stability and structure. In vitro experiments showed that this system significantly downregulated Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) in triple-negative breast cancer cells and inhibited their proliferation. Molecular docking simulations revealed the biological effects of CP1 are derived from its carboxyl groups. Using reinforcement learning, multiple new derivatives were generated from this compound, displaying excellent biological activities. These findings highlight the potential clinical applications and the innovative capacity of this nanocarrier system in drug development.

Angiotensin 1 peptide-conjugated CdSe/ZnS quantum dots for cardiac-specific hydrogen sulfide targeted therapy in myocardial ischemia-reperfusion injury.

Introduction: Myocardial ischemia/reperfusion (I/R) injury remains a major obstacle in cardiovascular therapies. Hydrogen sulfide (H2S) shows promise for mitigating I/R injury, but conventional delivery methods, such as NaHS injections or adenovirus-mediated CSE gene therapy, face low efficiency and systemic side effects. This study explores the use of angiotensin 1 (AT1) peptide-conjugated CdSe/ZnS quantum dots (QDs) for targeted delivery of cystathionine-γ-lyase (CSE) plasmids to the myocardium, aiming to boost local H2S production and minimize I/R injury. Methods: CdSe/ZnS QDs were conjugated with AT1 peptides to create a nanocarrier system capable of delivering the CSE plasmid specifically to the myocardium. In vivo fluorescence imaging confirmed heart-specific accumulation. Myocardial infarct size, cardiac function, cell death, and oxidative stress were evaluated. Endoplasmic reticulum stress and mitophagy markers, including CHOP/GRP78/eIF2α, were analyzed, and the CHOP gene's role was further assessed using an adenovirus vector. Results: The AT1-conjugated nanocarriers significantly increased CSE expression in the myocardium, as confirmed by fluorescence imaging, without affecting other organs. This localized delivery reduced myocardial infarct size, improved cardiac function, and decreased oxidative stress and cell death. Importantly, a reduction in endoplasmic reticulum stress and mitophagy markers was observed, suggesting that cardioprotection was mediated via the CHOP/GRP78/eIF2α signaling pathway. Reintroduction of CHOP using an adenovirus vector reversed these protective effects, confirming the pathway's involvement. Discussion: This study demonstrates that AT1 peptide-conjugated QDs can effectively deliver CSE plasmids to the heart, providing significant protection against I/R injury through enhanced localized H2S production. This approach offers a promising, targeted, and side-effect-free therapy for myocardial I/R injury, with potential for clinical translation.

Nanoenabled Antiviral Pesticide for Tobacco Mosaic Virus: Excellent Adhesion Performance and Strong Inhibitory Effect to Alleviate the Damage on Photosynthetic System.

Tobacco mosaic virus (TMV) is a major agricultural threat. Here, a cationic star polymer (SPc) was designed to construct an efficient nanodelivery system for moroxydine hydrochloride (ABOB). ABOB could self-assemble with SPc via a hydrogen bond and van der Waals force, and this complexation reduced the particle size of ABOB from 2406 to 45 nm. With the aid of SPc, the contact angle of ABOB decreased from 100.8 to 79.0°, and its retention increased from 6.3 to 13.8 mg/cm2. Furthermore, the complexation with SPc could attenuate the degradation of ABOB in plants, and the bioactivity of SPc-loaded ABOB significantly improved with a reduction in relative viral expression from 0.57 to 0.17. The RNA-seq analysis revealed that the ABOB/SPc complex could up-regulate the expression of growth- and photosynthesis-related genes in tobacco seedlings, and the chlorophyll content increased by 2.5 times. The current study introduced an efficient nanodelivery system to improve the bioactivity of traditional antiviral agents.

Exploring intranasal drug delivery via nanocarriers: A promising glioblastoma therapy.

Glioblastoma is one of the most recurring types of glioma, having the highest mortality rate among all other gliomas. Traditionally, the standard course of treatment for glioblastoma involved maximum surgical resection, followed by chemotherapy and radiation therapy. Nanocarriers have recently focused on enhancing the chemotherapeutic administration to the brain to satisfy unmet therapeutic requirements for treating brain-related disorders. Due to the significant drawbacks and high recurrence rates of gliomas, intranasal administration of nanocarrier systems presents several advantages. These include low toxicity, non-invasiveness, and the ability to cross the blood-brain barrier. By customizing their size, encasing them with mucoadhesive agents, or undergoing surface modification that encourages movement over the nose's mucosa, we can exceptionally engineer nanocarriers for intranasal administration. Olfactory and trigeminal nerves absorb drugs administered nasally and transport them to the brain, serving as the primary delivery mechanism for nose-to-brain administration. This review sums up the latest developments in chemotherapeutic nanocarriers, such as metallic nanoparticles, polymeric nanoparticles, nanogels, nano vesicular carriers, genetic material-based nanocarriers, and polymeric micelles. These nanocarriers have demonstrated efficient drug delivery from the nose to the brain, effectively overcoming mucociliary clearance. However, challenges persist, such as limitations in targeted chemotherapy and restricted drug loading capacity for intranasal administration. Additionally, the review addresses regulatory considerations and prospects for these innovative drug delivery systems.

Targeted delivery of quercetin using gelatin/starch/Fe3O4 nanocarrier to suppress the growth of liver cancer HepG2 cells.

To suppress HepG2 liver cancer cells, a nanocarrier (NC) consisting of Fe3O4, Gelatin (G), and Starch (S) was synthesized and characterized for targeted delivery of Quercetin (QC) drug. The spectra obtained from X-ray diffraction (XRD) and Fourier transform infrared (FTIR) demonstrated that the nanoparticles (NP) in the NC are well-interconnected to each other and have formed a regular structure. Also, field emission scanning electron microscopy (FE-SEM) indicates a smooth and homogeneous surface of the synthesized NC. The results of the vibrating sample magnetometer (VSM) also corroborated the correctness of the synthesis of Fe3O4 NPs and Gelatin/Starch/Fe3O4@Quercetin NC (G/S/Fe3O4@QC) because the magnetic properties of Fe3O4 decreased with the addition of G/S@QC. Stability and particle size were determined by zeta potential and Dynamic light scattering (DLS). The percentage of drug loading and encapsulation efficiency of QC in the NC was 46.25 % and 87 %, respectively. QC profile release in acidic and natural environments showed controlled release and pH sensitivity of the NC. Cytotoxicity of L929 and HepG2 treated cells with the G/S/Fe3O4@QC was investigated by MTT staining, which agreed with the flow cytometry result. The results of Flowcytometry and MTT showed 43.5 % apoptosis and 42 % cytotoxicity in treated HepG2 cells by G/S/Fe3O4@QC, while it was not toxic to L929 normal cells. According to the results, G/S/Fe3O4@QC is a suitable NC for the targeted delivery of QC as a drug against HepG2 cancer cells.

Multi-Stimuli-Responsive Biocompatible Magnetic Nanocarrier as Drug Delivery System to MCF-7 Breast Cancer Cells.

INTRODUCTION: The last strategy in targeted drug delivery systems is to deliver the anticancer drug to the tumor tissue to increase its therapeutic effect and minimize its undesirable side effects. In line with this goal in this research, the redox/pH-responsive disulfide magnetic nanocarriers based on PF127-NH2/L-cysteine-CM-ß-CD-FA were synthesized and evaluated in a doxorubicin delivery system. METHODS: We effectively surrounded Fe3O4 nanoparticles with SiO2 using the sol-gel method, and then confidently coated them with oleic acid on Fe3O4@SiO2 nanoparticles.. In another reaction, a PF127-NH2/L-cysteine-CM-ß-CD-FA was synthesized. The process involved modifying pluronic F127 (PF 127) with maleic anhydride and aminating it to form PF127-NH2. The obtained PF127-NH2 was attached to L-cysteine, followed by condensing with carboxymethyl-ß-cyclodextrin and then functionalized by folic acid. Finally, PF127-NH2/L-cysteine-CM-ß-CD-FA was coated on the surface of magnetic nanoparticles, and the resulting PF127-NH2/L-cysteine-CM-ß-CD-FA was disulfidated to form the final nanocarrier network, which was abbreviated as LCMNPs-SS. The doxorubicin was used as a model drug and loaded into the LCMNPs-SS nanocarrier. RESULTS: The LCMNPs-SS nanocarrier exhibited excellent properties for controlled release, with a well-defined release rate, a controllable level by an external magnet, and adjusting by DLdithiothreitol concentration. The LCMNPs-SS nanocarrier could also break apart when exposed to an oxidant or a change in pH. This meant that the drug release could be fine-tuned in response to temperature, pH, or more than one stimulus. CONCLUSION: These drug-carrying systems are valuable in reducing the dose of doxorubicin. High internalization of the synthesized LCMNPs-SS caused sped cellular uptake.

A size-switchable microsphere loaded with salmon calcitonin as two-weekly dosing for osteoporosis therapy.

Osteoporosis is a disease with an increased incidence of fractures due to decreased bone mass and destruction of the microstructure of bone tissue. Salmon calcitonin (sCT), as a peptide, possesses the ability to inhibit osteoclast activity and thus regulate bone metabolism in clinical. However, short half-life and unstable physicochemical properties leading to rapid degradation of sCT have severely limited its clinical application. In this study, a size-switchable microsphere was developed to solve the problem of frequent administration and poor stability of sCT. sCT was encapsulated into Egg PC to form anhydrous reverse micelles (ARM) and then ARM was encapsulated into microspheres (MS@ARM). The degradable composite microspheres were utilized to provide a drug reservoir for sustained release of ARM encapsulated with sCT to reduce the frequency of drug administration, while the released ARM encapsulated with sCT entered the blood circulation to further protect sCT. In vitro release experiments demonstrated that the microspheres could sustain the release of sCT for at least 16 days. The microspheres MS@ARM showed the advanced therapeutic effect on the mouse model of glucocorticoid-induced osteoporosis (GIOP) at a low dosing frequency. The size-switchable microsphere is expected to be a new strategy for delivering sCT for osteoporosis treatment.

Dose-effect relationship of copolymer on enhancing aqueous lubrication of a hybrid osteoarthritis drug delivery nanocarrier.

Developing stimulus-responsive properties of drug delivery nanocarriers combined with enhanced joint lubrication is an effective synergistic strategy for treating osteoarthritis. Poly(N-isopropylacrylamide) (PNIPAm) is a typical thermo-responsive polymer, which can achieve drug delivery by transition from swollen state to collapsed state. However, undesired transition temperature, limited drug loading capacity, and weakened mechanical properties in joint present obstacles to use as drug delivery nanocarriers. In this work, we demonstrate dose-effect relationship between the PNIPAm-based copolymer and nanoscale metal-organic frameworks on enhancing both aqueous lubrication and drug delivery performance of a hybrid osteoarthritis (OA) nanocarrier. A series of NIPAm and poly(ethylene glycol)methacrylate (PEGMa) copolymer microgels with different feeding content are optimized to grow on the surface of MIL-101(Cr) nanoparticles via one-pot soap-free emulsion copolymerization method. By changing the feeding mass ratio of NIPAm and PEGMa, MIL-101(Cr)@P(NIPAm-g-PEGMax) (x = 0, 1, 2, 3, and 4, named MPNPx) hybrids can ameliorate the lower critical solution temperature to match with OA and enhance the aqueous lubrication performance. Among the as-synthesized hybrids, MPNP3 hybrids manifested the notable enhanced thermo-responsive tribological performance due to the synergistic effect of "hydration lubrication" and "ball-bearing" function of the optimized copolymer microgel layer on the surface of metal-organic frameworks (MOFs). Anti-inflammatory drug loading is enabled by the high surface area and porosity of the MOFs, and the MPNP3 drug delivery nanocarriers achieve thermo-responsive release in vitro. Our work establishes the dose-effect relationship between thermo-responsive NIPAm and hydrophilic PEGMa of the copolymer grown on the surface of MOFs, providing valuable insights for improving the versatility of stimuli-responsive for biomedical application.

Interferon gamma-gaillardin nanocomplex formation with improved anti-melanoma effects.

This study presents a comprehensive analysis of IFN-γ-Gaillardin nanoparticles (NPs) using a combination of computational, biophysical and cell-based approaches. The molecular docking analysis revealed that both hydrogen and hydrophobic forces are involved in the formation of IFN-γ-Gaillardin complex The interaction between IFN-γ and Gaillardin was further characterized by a pronounced ANS fluorescence spectrum peak and a higher intensity for IFN-γ. The Langmuir, Scatchard, and Hill analyses revealed a higher affinity and lower dissociation constant for IFN-γ NPs compared to IFN-γ alone, suggesting enhanced complex stability. Thermal gravimetric analysis confirmed that the Gaillardin interaction might improve the thermal stability of the NPs. The NPs demonstrated robust stability in various media, highlighting their potential as a delivery system. However, size increase in deionized water suggests the need for formulation optimization. Cell-based assays revealed selective cytotoxicity towards A-375 melanoma cancer cells with minimal impact on non-cancerous HaCaT cells, indicating targeted antitumor effects. Real-time PCR showed gene expression changes consistent with antitumor activity and immune response modulation. The findings suggest that IFN-γ-Gaillardin NPs have potent antitumor properties and the ability to modulate the immune system, warranting further investigation into their therapeutic applications. The development of an IFN-γ-based nanocarrier system for Gaillardin delivery offers a promising approach to melanoma therapy, setting a new direction for NP-based cancer treatment strategies.

Nanomedicine in HNSCC therapy-a challenge to conventional therapy.

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field.

Size-dependent translocation and lymphatic transportation of polymeric nanocarriers post intraperitoneal administration.

Intraperitoneal (i.p.) administered nanomedicine has been widely applied in the clinical treatment of intra-abdominal diseases and preclinical pharmacological investigations. However, current understandings about the in vivo fate of i.p.-administered drug remains controversial owing to lack of reliable investigation tools. This work presents a nanoparticle-labeling strategy based on aggregation-caused quenching (ACQ) probes in the second near-infrared (NIR-II) window, which can eliminate the interference of unbound probes and allow for non-invasive tracking of nanoparticles in deep tissues. Our results strongly evidence a size-dependent absorption and biodistribution of the i.p.-administered polymeric nanocarriers (PNs) with particle sizes ranging from 30 to 1000 nm both in vivo and ex vivo, and moreover provide a clear visualization of lymphatic transportation and lymph node retention of integral PNs. Importantly, our findings suggest that small particles (≤30 nm) are favorable in systemic therapies due to their rapid absorption and high concentration (>19 %ID mL-1) in circulation, while large particles (over 1000 nm) are meant for localized treatment of abdominal diseases. Besides, the high retention of 200 nm nanoparticles within lymph nodes indicates their promising role in cancer vaccines and lymphatic diseases including lymph node metastasis.

GABA-Decorated Nanocarrier for Smart Delivery of Fludioxonil for Targeted Control of Banana Wilt Disease.

Developing a targeted nanopesticide to control the vascular disease of banana in agriculture is crucial to improve pesticide utilization. In this study, according to the degree of functionalization, three γ-aminobutyric acid (GABA)-decorated nanocarriers (PSI-GABA8, PSI-GABA18, and PSI-GABA28) were constructed for smart delivery of nonsystemic fungicide in banana phloem tissues. Fludioxonil (Flu) was loaded in nanocarriers to form Flu@PSI-GABA nanoparticles with a core/shell structure for control of banana wilt disease. Results demonstrated that the delivery dosage of Flu was up to 1.6 mg/L in castor phloem sap using PSI-GABA28 nanocarriers. In vitro results showed that the EC50 of Flu@PSI-GABA28 was 0.0116 mg/L, and the inhibitory activity was about 8.8 times higher than that of technical-grade (TC) Flu. Flu@PSI-GABA28 could be transported for long distances and accumulated to the rhizome of banana by foliar application, and the control effectiveness was about 20 times that of the conventional Flu (50% WP) for the banana wilt. This study provides a distinctive guidance for effective control of vascular diseases in precision agriculture application.

Supramolecular nanoparticle loaded with bilirubin enhances cartilage protection and alleviates osteoarthritis via modulating oxidative stress and inflammatory responses.

Osteoarthritis (OA) is a chronic inflammation that gradually leads to cartilage degradation. Prolonged chondrocyte oxidative stress contributes to the development of diseases, including chondrocyte apoptosis, cartilage matrix degradation, and aggravation of articular cartilage damage. Bilirubin (BR) possesses strong antioxidant properties by scavenging reactive oxygen species (ROS) and potent protection effects against inflammation. However, its insolubility and short half-life limit its clinical use. Therefore, we developed a supramolecular system of ε-polylysine (EPL) conjugated by ß-cyclodextrin (ß-CD) on the side chain, and bilirubin was loaded via host-guest interactions, which resulted in the self-assemble of this system into bilirubin-loaded polylysine-ß-cyclodextrin nanoparticle (PB) with improving solubility while reducing toxicity and prolonging medication action time. To explore PB's potential pharmacological mechanisms on OA, we established in vitro and in vivo OA models. PB exerted ROS-scavenging proficiency and anti-apoptotic effects on rat chondrocytes by activating the Nrf2-HO-1/GPX4 signaling pathway. Additionally, PB reprogrammed the cartilage microenvironment by regulating the NF-κB signaling pathway to maintain chondrocyte function. Animal experiments further confirmed that PB had excellent scavenging ability for ROS and inflammatory factors related to charge adsorption with cartilage as well as long retention ability. Together, this work suggests that PB has superior protective abilities with beneficial effects on OA, indicating its great potential for intervention therapy targeting chondrocytes.

Tityus stigmurus-Venom-Loaded Cross-Linked Chitosan Nanoparticles Improve Antimicrobial Activity.

The rapid resistance developed by pathogenic microorganisms against the current antimicrobial pool represents a serious global public health problem, leading to the search for new antibiotic agents. The scorpion Tityus stigmurus, an abundant species in Northeastern Brazil, presents a rich arsenal of bioactive molecules in its venom, with high potential for biotechnological applications. However, venom cytotoxicity constitutes a barrier to the therapeutic application of its different components. The objective of this study was to produce T. stigmurus-venom-loaded cross-linked chitosan nanoparticles (Tsv/CN) at concentrations of 0.5% and 1.0% to improve their biological antimicrobial activity. Polymeric nanoparticles were formed with a homogeneous particle size and spherical shape. Experimental formulation parameters were verified in relation to mean size (<180 nm), zeta potential, polydispersity index and encapsulation efficiency (>78%). Tsv/CN 1.0% demonstrated an ability to increase the antimicrobial venom effect against Staphylococcus aureus bacteria, exhibiting an MIC value of 44.6 µg/mL. It also inhibited different yeast species of the Candida genus, and Tsv/CN 0.5% and 1.0% led to a greater inhibitory effect of C. tropicalis and C. parapsilosis strains, presenting MIC values between 22.2 and 5.5 µg/mL, respectively. These data demonstrate the biotechnological potential of these nanosystems to obtain a new therapeutic agent with potential antimicrobial activity.

Recent Developments in Personal Glucose Meters as Point-of-Care Testing Devices (2020-2024).

Point-of-care testing (POCT) is a contemporary diagnostic approach characterized by its user-friendly nature, cost efficiency, environmental compatibility, and lack of reliance on professional experts. Therefore, it is widely used in clinical diagnosis and other analytical testing fields to meet the demand for rapid and convenient testing. The application of POCT technology not only improves testing efficiency, but also brings convenience and benefits to the healthcare industry. The personal glucose meter (PGM) is a highly successful commercial POCT tool that has been widely used not only for glucose analysis, but also for non-glucose target detection. In this review, the recent advances from 2020 to 2024 in non-glucose target analysis for PGMs as POCT devices are summarized. The signal transduction strategies for non-glucose target analysis based on PGMs, including enzymatic transduction, nanocarrier transduction (enzyme or glucose), and glucose consumption transduction are briefly introduced. Meanwhile, the applications of PGMs in non-glucose target analysis are outlined, encompassing biomedical, environmental, and food analysis, along with other diverse applications. Finally, the prospects of and obstacles to employing PGMs as POCT tools for non-glucose target analysis are discussed.

Interactions of human serum albumin with phosphate and Tris buffers: impact on paclitaxel binding and nanoparticles self-assembly.

AIM: To investigate the conformational changes in human serum albumin (HSA) caused by chemical (CD) and thermal denaturation (TD) at pH 7.4 and 9.9, crucial for designing controlled drug delivery systems with paclitaxel (PTX). METHODS: Experimental and computational methods, including differential scanning calorimetry (DSC), UV-Vis and intrinsic fluorescence spectroscopy, mean diameter, polydispersity index (PDI), ζ-potential, encapsulation efficiency (EE), in vitro release and protein docking studies were conducted to study the HSA denaturation and nanoparticles (NPs) preparation. RESULTS: TD at pH 7.4 produced smaller NPs (287.1 ± 12.9 nm) than CD at pH 7.4 with NPs (584.2 ± 47.7 nm). TD at pH 9.9 exhibited high EE (97.3 ± 0.2%w/w) with rapid PTX release (50% within 1h), whereas at pH 7.4 (96.4 ± 2.1%w/w), release only 40%. ζ-potentials were around -30 mV. CONCLUSION: Buffer type and pH significantly influence NP properties. TD in PBS at pH 7.4, provided optimal conditions for a stable and efficient drug delivery system.