89Zr-Labeled DFO@Durvalumab-HSA nanoparticles: In vitro potential for triple-negative breast cancer.

This study presents the development and evaluation of a DFO@mAb-NP (DFO@Durvalumab-HSA-DTX nanoparticle) nanoplatform for imaging in triple-negative breast cancer (TNBC). The nanoplatform demonstrated significant changes postconjugation with DFO, evidenced by increased particle size from 178.1 ± 5 nm to 311 ± 26 nm and zeta potential alteration from -31.9 ± 3 mV to -40.5 ± 0.8 mV. Fourier-transform infrared spectroscopy and ultraviolet spectral analyses confirmed successful DFO conjugation, with notable shifts in peak wavelengths. High labeling efficiency was achieved with 89Zr, as indicated by thin layer radio chromatography and high-performance liquid radio chromatography results, with labeling efficiencies of 98 ± 2% for 89Zr-DFO@mAb and 96 ± 3% for 89Zr-DFO@mAb-NP. The nanoplatforms maintained stability over 24 h, showing less than 5% degradation. Lipophilicity assays revealed logP values of 0.5 ± 0.03 for 89Zr-DFO@mAb-NP and 0.98 ± 0.2 for 89Zr-DFO@mAb, indicating a higher lipophilic tendency in the radiolabeled Durvalumab. Cell uptake experiments showed an initial high uptake in MDA-MB-468 cells (45.1 ± 3.2%), which decreased over time, highlighting receptor-specific interactions. These comprehensive findings suggest the promising potential of the DFO@mAb-NP nanoplatform for targeted imaging in TNBC, with implications for improved diagnostic accuracy and treatment strategies.

Optimizing Desolvation Conditions for Glutathione-Cross-Linked Bovine Serum Albumin Nanoparticles: Implication for Intravenous Drug Delivery.

INTRODUCTION: Protein-based nanocarriers, particularly albumin nanoparticles (NPs), offer numerous advantages when compared to other nanomaterials. These carriers are characterized by biocompatibility, biodegradability, reduced immunogenicity, and decreased cytotoxicity. Moreover, proteins possess an inherent ability to target tumor cells directly or indirectly. AIM: This study aims to investigate the impact of various organic solvents on the characteristics of synthesized bovine serum albumin NPs (BSA NPs). METHOD: BSA NPs were produced using methanol, acetone, ethanol, dimethylsulfoxide (DMSO), and acetonitrile through the desolvation technique to achieve particles of acceptable size. Dynamic light scattering (DLS), blood compatibility assays, polyacrylamide gel electrophoresis (PAGE), and size exclusion chromatography (SEC) were employed to elucidate the properties of the generated NPs. The cytotoxicity of BSA NPs prepared under different conditions was assessed using Michigan Cancer Foundation - Mammary Adenocarcinoma - Breast Cancer 231 cells (MDA-MB-231 cells). RESULTS: The particle size of the synthesized NPs varied based on the organic solvent utilized, with the smallest size of 114.2 nm observed with methanol. Blood compatibility results indicated no abnormal interactions between BSA NPs and blood components. PAGE analysis revealed a strong band near 72 kDa for untreated BSA and BSA treated with all organic solvents. In SEC, the retention time of native albumin was 6.65 min, while the average retention times of the prepared BSA NPs ranged from 5.14 to 5.21 min, showing similarity to the native protein. Except for NPs produced with methanol and acetonitrile, cytotoxicity testing on MDA-MB-231 cells demonstrated no significant harmful effects at various concentrations (0-500 µg/mL). CONCLUSION: The choice of desolvating agent significantly influences the size of BSA NPs. Various factors, such as solvent characteristics like hydrogen bonds, polarity, dielectric constant, and functional groups, can affect the particle size and structure of BSA NPs. The compatibility of cross-linked BSA NPs with blood components suggests their potential for intravenous drug delivery applications.

Piperine and piperine-loaded albumin nanoparticles ameliorate adjuvant-induced arthritis and reduce IL-17 in rats.

AIM: Rheumatoid arthritis (RA) is one of the most common chronic, inflammatory, autoimmune diseases affecting mainly the joints. Piperine (PIP), an alkaloid found in black pepper, has anti-inflammatory properties and its use in drug delivery systems such as nanoparticles might be a treatment for RA. This study aims to evaluate the possible anti-inflammatory and anti-arthritic effects of PIP and its use in albumin nanoparticles as a possible approach for the treatment of Adjuvant-induced arthritis (AIA) rats. METHODS: PIP-loaded Bovine Serum Albumin nanoparticles (PIP-BSA NPs) were prepared using a desolvation method. AIA rats were given intraperitoneal injections of either 40 mg PIP or 131 mg PIP-BSA NPs every two days until day 28 when animals were sacrificed. Clinical score, histopathology, X-ray radiography, and serum levels of pro-inflammatory cytokines such as IL-1ß, IL-17, and TNF-α were evaluated. RESULTS: PIP and PIP-BSA NPs significantly reduced clinical scores, and alleviated inflammation within the joints. PIP was superior to PIP-BSA NPs for the alleviation of fibrin deposition and periosteal reactions while bone inflammation and erosion were less severe in the case of PIP-BSA NPs. Besides, both of the treatments suppressed serum levels of IL-17 in AIA rats (p = 0.003 and p = 0.02; respectively). CONCLUSIONS: PIP and PIP-BSA NPs effectively alleviate the severity of AIA and suppress inflammation. Due to the superiority of PIP in improving fibrin deposition and periosteal reactions and the efficacy of PIP-BSA NPs in suppressing bone inflammation and erosion, their simultaneous use might be investigated.

Removal of the nalidixic acid antibiotic from aqueous solutions using bovine serum albumin nanoparticles.

The presence of antibiotic pollutants in water and wastewater can cause significant risks to the environment in different aspects. Therefore, antibiotics need to be removed from water. This study investigates the adsorption of nalidixic acid (NA), a common antibiotic, using bovine serum albumin nanoparticles (BSA NPs). These NPs were synthesized via desolvation technique and characterized using SEM, DLS, FT-IR, and UV-Vis spectroscopy. The effects of adsorbent dosage (0.02-0.9 mg), initial NA concentration (30-80 mg L- 1) and contact time (0.5-24 h) on adsorption efficiency were considered. Adsorption isotherms and kinetics were determined experimentally. The Freundlich isotherm best described the adsorption equilibrium, while the pseudo-second-order kinetic model accurately represented the adsorption process. Thermodynamic parameters confirmed the spontaneous and exothermic nature of NA adsorption onto BSA NPs. Under optimal conditions, BSA NPs achieved a removal efficiency of 75% for NA with a maximum adsorption capacity of 240 mg g- 1. These results demonstrate the potential of BSA NPs as an effective adsorbent for removing NA from aqueous solutions.

Serum Albumin in Nasal Drug Delivery Systems: Exploring the Role and Application.

The application of serum albumin in various types of formulations has emerged as a valuable option in biomedical research, especially in the field of nasal drug delivery systems. A serum albumin-based carrier system has been employed due to several benefits, such as enhancing drug solubility and stability, generating the desired controlled release profile, and developing favorable properties with respect to the challenges in nasal conditions, which, in this case, involves hindering rapid elimination due to nasal mucociliary clearance. Accordingly, considering the important role of serum albumin, in-depth knowledge related to its utilization in preparing nasal drug formulation is highly encouraged. This review aimed to explore the potential application of serum albumin in fabricating nasal drug formulations and its crucial role and functionality regarding the binding interaction with nasal mucin, which significantly determines the successful administration of nasal drug formulations.

A Novel ANG-BSA/BCNU/ICG MNPs Integrated for Targeting Therapy of Glioblastoma.

PURPOSE: Develop an albumin nanoparticle-based nanoprobe for targeted glioblastoma (GBM) diagnosis and treatment, utilizing Angopep-2 for low-density lipoprotein receptor-related protein (LRP) targeting. METHODS: Combined albumin-coated superparamagnetic iron oxide (SPIO), Carmustine (BCNU), and indocyanine green (ICG). Assessed morphology, size, Zeta potential, fluorescence, and drug encapsulation. Conducted in vitro fluorescence/MRI imaging and cell viability assays, and in vivo nanoprobe accumulation evaluation in brain tumors. RESULTS: ANG-BSA/BCNU/ICG MNPs exhibited superior targeting and cytotoxicity against GBM cells in vitro. In vivo, enhanced brain tumor accumulation during imaging was observed. CONCLUSION: This targeted imaging and drug delivery system holds promise for efficient GBM therapy and intraoperative localization, addressing Blood-brain barrier (BBB) limitations with precise drug delivery and imaging capabilities.

Improving the Thrombocytopenia Adverse Reaction of Belinostat Using Human Serum Albumin Nanoparticles.

Background: Belinostat, a histone deacetylase inhibitor used for hematological cancer treatments, however, it caused thrombocytopenia, poor solubility, and rapid clearance. To mitigate these issues, human serum albumin (HSA) was utilized as the core material for its high protein binding affinity and self-binding capabilities. The study focused on developing belinostat-loaded HSA nanoparticles to improve solubility, extend circulation time, and reduce adverse effects. Methods: Belinostat-loaded HSA nanoparticles were synthesized using a desolvation method, optimized for size, charge, and entrapment efficiency, and characterized by molecular docking and Fourier-transform infrared spectroscopy (FTIR). Cytotoxicity was assessed in vitro against HuT-78 cells, and in vivo pharmacokinetics and toxicology studies were conducted to evaluate therapeutic efficacy and safety. Results: The prepared belinostat-HSA nanoparticles exhibited the size of 150 nm with a charge of ~-50 mV and a high entrapment efficiency (90%). Molecular docking confirmed that belinostat and HSA had a strong binding affinity (-9.5 kcal mol-1), and the entrapment of belinostat within HSA nanoparticles was also confirmed via FTIR. Belinostat-HSA nanoparticles were cytotoxic against HuT-78 with the dose-response relation (1-100 µM). The highly concentrated (100 µM) belinostat-HSA nanoparticles maintained the viability of the peripheral blood mononuclear cells with 50% survival, which did not survive when exposed to belinostat (100 µM). The belinostat-HSA nanoparticles proved suitable for intravenous administration without causing hemolysis, exhibited prolonged circulation times, and improved in vivo platelet counts significantly (p < 0.05). Conclusion: In conclusion, the belinostat-loaded HSA nanoparticles significantly enhance the solubility and half-life of belinostat, reduce its adverse hematological effects, and maintain sustained drug release. These attributes underscore the potential of belinostat-HSA nanoparticles as a viable intravenous option for the treatment of hematological malignancies.

Application of galactosylated albumin for targeted delivery of triptolide to suppress hepatocellular carcinoma progression through inhibiting de novo lipogenesis.

Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-associated death globally with a lack of efficient therapy. The pathogenesis of HCC is a complex and multistep process, highly reliant on de novo lipogenesis, from which tumor cells can incorporate fatty acids to satisfy the necessary energy demands of rapid proliferation and provide survival advantages. Triptolide (TP) is a bioactive ingredient exhibiting potent abilities of anti-proliferation and lipid metabolism regulation, but its clinical application is constrained because of its toxicity and non-specific distribution. The present study has developed galactosylated bovine serum albumin nanoparticles loaded with TP (Gal-BSA-TP NPs) to alleviate systemic toxicity and increase tumor-targeting and antitumor efficacy. Furthermore, Gal-BSA-TP NPs could inhibit de novo lipogenesis via the p53-SREBP1C-FASN pathway to deprive the fuel supply of HCC, offering a specific strategy for HCC treatment. In general, this study provided a biocompatible delivery platform for targeted therapy for HCC from the perspective of de novo lipogenesis.

Trend of albumin nanoparticles in oncology: a bibliometric analysis of research progress and prospects.

Background: Delivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective. Methods: Using the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted. Results: From 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included "rapid and convenient synthesis methods predominated by self-assembly," "surface modification," "construction of multifunctional NPs for theranostics," "research on natural active ingredients mainly based on phenolic compounds," "combination therapy," and "clinical applications." Conclusion: Based on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.

Self-Sulfhydrated, Nitro-Fixed Albumin Nanoparticles as a Potent Therapeutic Agent for the Treatment of Acute Liver Injury.

Exogenous polysulfhydryls (R-SH) supplementation and nitric oxide (NO) gas molecules delivery provide essential antioxidant buffering pool components and anti-inflammatory species in cellular defense against injury, respectively. Herein, the intermolecular disulfide bonds in bovine serum albumin (BSA) molecules were reductively cleaved under native and mild conditions to expose multiple sulfhydryl groups (BSA-SH), then sulfhydryl-nitrosylated (R-SNO), and nanoprecipitated to form injectable self-sulfhydrated, nitro-fixed albumin nanoparticles (BSA-SNO NPs), allowing albumin to act as a NO donor reservoir and multiple sulfhydryl group transporter while also preventing unfavorable oxidation and self-cross-linking of polysulfhydryl groups. In two mouse models of ischemia/reperfusion-induced and endotoxin-induced acute liver injury (ALI), a single low dosage of BSA-SNO NPs (S-nitrosothiols: 4 µmol·kg-1) effectively attenuated oxidative stress and systemic inflammation cascades in the upstream pathophysiology of disease progression, thus rescuing dying hepatocytes, regulating host defense, repairing microcirculation, and restoring liver function. By mechanistically upregulating the antioxidative signaling pathway (Nrf-2/HO-1/NOQ1) and inhibiting the inflammatory cytokine storm (NF-κB/p-IκBα/TNF-α/IL-ß), BSA-SNO NPs blocked the initiation of the mitochondrial apoptotic signaling pathway (Cyto C/Bcl-2 family/caspase-3) and downregulated the cell pyroptosis pathway (NLRP3/ASC/IL-1ß), resulting in an increased survival rate from 26.7 to 73.3%. This self-sulfhydrated, nitro-fixed functionalized BSA nanoformulation proposes a potential drug-free treatment strategy for ALI.

Dexamethasone Palmitate Encapsulated in Palmitic Acid Modified Human Serum Albumin Nanoparticles for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory joint condition characterized by symmetric, erosive synovitis leading to cartilage erosion and significant disability. Macrophages, pivotal in disease progression, release pro-inflammatory factors upon activation. We developed a nanoparticle delivery system (DXP-PSA NPs), based on palmitic acid modified human serum albumin (PSA), to deliver dexamethasone palmitate (DXP) directly to sites of inflammation, enhancing treatment effectiveness and minimizing possible side effects. The system actively targets scavenger receptor-A on activated macrophages, achieving selective accumulation at inflamed joints. In vitro effect and preliminary targeting abilities were investigated on LPS-activated RAW264.7 cells. The in vivo efficacy and safety were evaluated and compared side to side with commercially available lipid emulsion Limethason® in an advanced adjuvant-induced arthritis rat model. DXP-PSA NPs offer a novel approach to RA treatment and presents promising prospects for clinical translation.

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

Biomimetic Cancer-Targeting Nanoplatform Boosting AIEgens-Based Photodynamic Therapy and Ferroptosis by Disrupting Redox-Homeostasis.

Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSADSP@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.

Albumin-seeking dyes with adjustable assemblies in situ enable programmable imaging windows and targeting tumor imaging.

Cyanine dyes are widely used organic probes for in vivo imaging due to their tunable fluorescence. They can form complexes with endogenous albumin, resulting in enhanced brightness and photostability. However, this binding is uncontrollable and irreversible, leading to considerable nonspecific background signals and unregulated circulation time. Methods: Here, we connect varying numbers of 4-(4-iodophenyl) butanoic acid (IP) as albumin-binding moieties (ABM) to the cyanine dye, enabling dynamic and controllable binding with albumin. Meanwhile, we provide a blocking method to completely release the dye from covalent capture with albumin, resulting in specific targeting fluorescence. Furthermore, we evaluate the pharmacokinetics and tumor targeting of the developed dyes. Results: The engineered dyes can dynamically and selectively bind with multiple albumins to change the in situ size of assemblies and circulation time, providing programmable regulation over the imaging time window. The nucleophilic substitution of meso-Cl with water-soluble amino acids or targeting peptides for IP-engineered dye further addresses the nonspecific signals caused by albumin, allowing for adjustable angiography time and efficient tumor targeting. Conclusion: This study rationalizes the binding modes of dyes and proteins, applicable to a wide range of near-infrared (NIR) dyes for improving their in vivo molecular imaging.

An oral bioactive chitosan-decorated doxorubicin nanoparticles/bacteria bioconjugates enhance chemotherapy efficacy in an in-situ breast cancer model.

Breast cancer is the second leading cause of cancer-related deaths among women worldwide. Despite significant advancements in chemotherapy, its effectiveness is often limited by poor drug distribution and systemic toxicity caused by the weak targeting ability of conventional therapeutic agents. The hypoxic tumor microenvironment (TME) also plays a vital role in treatment outcomes. Oral anticancer therapeutic agents have gained popularity and show promising results due to their ease of repeated administration. This study introduces autopilot biohybrids (Bif@BDC-NPs) for the effective delivery of doxorubicin (DOX) to the tumor site. This hybrid combines albumin-encapsulated DOX nanoparticles (BD-NPs) coated with chitosan (CS) for breast cancer chemotherapy, along with anaerobic Bifidobacterium infantis (B. infantis, Bif) serving as self-propelled motors. Due to Bif's specific anaerobic properties, Bif@BDC-NPs precisely anchor hypoxic regions of tumor tissue and significantly increase drug accumulation at the tumor site, thereby promoting tumor cell death. In an in-situ mouse breast cancer model, Bif@BDC-NPs achieved 94 % tumor inhibition, significantly prolonging the median survival of mice to 62 days, and reducing the toxic side effects of DOX. Therefore, the new bacteria-driven oral drug delivery system, Bif@BDC-NPs, overcomes multiple physiological barriers and holds great potential for the precise treatment of solid tumors.

Nanoparticles integrated with mild photothermal therapy and oxaliplatin for tumor chemotherapy and immunotherapy.

Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.

Reproducible Synthesis of Biocompatible Albumin Nanoparticles Designed for Intra-articular Administration of Celecoxib to Treat Osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis, with intra-articular (IA) delivery of therapeutics being the current best option to treat pain and inflammation. However, IA delivery is challenging due to the rapid clearance of therapeutics from the joint and the need for repeated injections. Thus, there is a need for long-acting delivery systems that increase the drug retention time in joints with the capacity to penetrate OA cartilage. As pharmaceutical utility also demands that this is achieved using biocompatible materials that provide colloidal stability, our aim was to develop a nanoparticle (NP) delivery system loaded with the COX-2 inhibitor celecoxib that can meet these criteria. We devised a reproducible and economical method to synthesize the colloidally stable albumin NPs loaded with celecoxib without the use of any of the following conditions: high temperatures at which albumin denaturation occurs, polymer coatings, oils, Class 1/2 solvents, and chemical protein cross-linkers. The spherical NP suspensions were biocompatible, monodisperse with average diameters of 72 nm (ideal for OA cartilage penetration), and they were stable over 6 months at 4 °C. Moreover, the NPs loaded celecoxib at higher levels than those required for the therapeutic response in arthritic joints. For these reasons, they are the first of their kind. Labeled NPs were internalized by primary human articular chondrocytes cultured from the knee joints of OA patients. The NPs reduced the concentration of inflammatory mediator prostaglandin E2 released by the primaries, an indication of retained bioactivity following NP synthesis. Similar results were observed in lipopolysaccharide-stimulated human THP-1 monocytes. The IA administration of these NPs is expected to avoid side-effects associated with oral administration of celecoxib and to maintain a high local concentration in the knee joint over a sustained period. They are now ready for evaluation by IA administration in animal models of OA.

Enhancing Paclitaxel Efficacy with Piperine-Paclitaxel Albumin Nanoparticles in Multidrug-Resistant Triple-Negative Breast Cancer by Inhibiting P-Glycoprotein.

Triple-negative breast cancer (TNBC) is a highly aggressive disease with rapid progression and poor prognosis due to multidrug resistance (MDR). Piperine (PIP) shows promise as a P-gp inhibitor, capable of sensitizing chemotherapeutic drugs and exhibiting antitumor properties. This study explores the inhibitory mechanism of PIP on P-glycoprotein (P-gp) and its capacity to enhance the sensitivity of paclitaxel (PTX). We subsequently evaluated the efficacy and safety of albumin nanoparticles that co-encapsulate PTX and PIP (PP@AN). The results demonstrated that PIP enhanced the accumulation of PTX intracellularly, as determined with HPLC/MS/MS analysis. PIP was also found to increase cell sensitivity to PTX. Furthermore, we explored the inhibitory mechanism of PIP on P-gp, utilizing molecular docking simulations, RT-qPCR, and Western blot analysis. PIP appears to compete with the active paclitaxel binding site on P-gp, affecting ATPase activity and downregulating the MDR1 gene and P-gp expression. In summary, PIP could inhibit P-gp and act as a sensitizer in the treatment of TNBC with PTX. Moreover, stable and uniform PP@AN was successfully formulated, resulting in a significant increase in drug accumulation within cells as well as the downregulation of P-gp in tumors at the optimal ratio (PTX:PIP = 1:2). This led to an improvement in the antitumor effect in vivo while also reducing hepatotoxicity and hemototoxicity following chemotherapy. This study comprehensively investigated PIP's inhibitory effect and mechanism on P-gp. We present a new approach for co-delivering PIP and PTX using albumin nanoparticles, which reduced toxicity and improved therapeutic efficacy both in vivo and in vitro.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Effect of variables on exemestane-loaded albumin nanoparticles: statistical optimization and anti-cancer activity in MCF-7 cell lines.

This research aimed to evaluate the effect of variables on exemestane-loaded bovine serum albumin nanoparticles (EXE-BSA NPs) to improve anti-breast cancer activity. EXE-BSA NPs were optimized using 32 factorial design, wherein the concentration of BSA (X1) and sonication time (X2) were independent variables and particle size (Y1) and %w/w entrapment efficiency (Y2) were dependent variables. The statistical optimization revealed a significant effect of BSA concentration on both variables, whereas sonication time affected only particle size. The optimized EXE-BSA NPs were spherical with 124.1 ± 2.62 nm particle size, 83.95 ± 1.06% w/w drug entrapment, and exhibited a biphasic release of 100% (w/w) drug over 72 h. The optimized formulation induced cytotoxicity in MCF-7 cell lines with an IC50 value of 21.46 µg/mL by MTT assay, almost half the free drug (54.87 µg/mL). Thus, statistically optimized EXE-BSA NPs were effective in MCF-7 cell lines and can be explored to treat estrogen receptor-positive breast cancer.