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Journal of Nanobiotechnology Jun 2024Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous...
Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([Ac]Ac). Encapsulation of [Ac]Ac within PLGA nanoparticles (Z = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [Ac]Ac. Chelation of [Ac]Ac to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [Ac]AcBLPhen significantly increased the delivery of [Ac]Ac to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [Ac]Ac in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.
Topics: Nanoparticles; Polylactic Acid-Polyglycolic Acid Copolymer; Actinium; Humans; Cell Line, Tumor; Animals; Alpha Particles; Mice; Female; Biocompatible Materials; Breast Neoplasms; Radioimmunotherapy
PubMed: 38825717
DOI: 10.1186/s12951-024-02520-6 -
Food Research International (Ottawa,... Jul 2024The emulsifying potential of a biocompatible ionic liquid (IL) to produce lipid-based nanosystems developed to enhance the bioaccessibility of cannabidiol (CBD) was...
Enhancing cannabidiol bioaccessibility using ionic liquid as emulsifier to produce nanosystems: Characterization of structures, cytotoxicity assessment, and in vitro digestion.
The emulsifying potential of a biocompatible ionic liquid (IL) to produce lipid-based nanosystems developed to enhance the bioaccessibility of cannabidiol (CBD) was investigated. The IL (cholinium oleate) was evaluated at concentrations of 1 % and 2 % to produce nanoemulsions (NE-IL) and nanostructured lipid carriers (NLC-IL) loaded with CBD. The IL concentration of 1 % demonstrated to be sufficient to produce both NE-IL and NLC-IL with excellent stability properties, entrapment efficiency superior to 99 %, and CBD retention rate of 100 % during the storage period evaluated (i.e. 28 days at 25 °C). The in vitro digestion evaluation demonstrated that the NLC-IL provided a higher stability to the CBD, while the NE-IL improved the CBD bioaccessibility, which was mainly related to the composition of the lipid matrices used to obtain each nanosystem. Finally, it was observed that the CBD cytotoxicity was reduced when the compound was entrapped into both nanosystems.
Topics: Cannabidiol; Ionic Liquids; Emulsifying Agents; Humans; Emulsions; Digestion; Nanostructures; Cell Survival; Biological Availability; Nanoparticles; Drug Carriers; Caco-2 Cells; Particle Size
PubMed: 38823878
DOI: 10.1016/j.foodres.2024.114498 -
Biomedicine & Pharmacotherapy =... Jul 2024Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine...
Luteolin, a monomeric substance, is a natural product of the Brucea javanica (BJ) plant. Brucea javanica oil emulsion injection (BJOEI) is a proprietary Chinese medicine purified from BJ that is widely used clinically as an anti-tumor treatment. Although a growing body of research suggests that luteolin and BJOEI have anti-tumor effects, the molecular mechanism of action has not been fully elucidated. In this study, through molecular docking technology, we found that luteolin can interact directly with GPSM2 and regulate the FoxO signaling pathway through GPSM2. In addition, the inhibitory effect of luteolin on colon adenocarcinoma (COAD) cells was found to be offset by knockdown of GPSM2. In contrast, the anti-proliferative effects of luteolin could be notably reversed by overexpression of GPSM2. The results reveal that GPSM2 is crucial in luteolin-mediated anti-proliferative effects. The mediation of anti-proliferative effects by GPSM2 has also been indirectly demonstrated in RKO and SW480 xenograft mice models. In addition, we verified that BJOEI inhibits the progression of COAD by mediating GPSM2 and regulating the FoxO signaling pathway. We also found that BJOEI achieved a better anti-tumor effect when combined with fluorouracil injection. Collectively, our data show that the anti-tumor effects of BJOEI and luteolin on COAD are GPSM2-dependent and downregulating the expression of GPSM2 to regulate the FoxO signaling pathway may be an effective way to treat COAD.
Topics: Luteolin; Humans; Animals; Colonic Neoplasms; Fluorouracil; Cell Line, Tumor; Adenocarcinoma; Cell Proliferation; Mice, Nude; Xenograft Model Antitumor Assays; Mice, Inbred BALB C; Signal Transduction; Mice; Biological Products; Gene Expression Regulation, Neoplastic; Molecular Docking Simulation
PubMed: 38823277
DOI: 10.1016/j.biopha.2024.116847 -
International Journal of Food... Aug 2024The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P....
The study prepared and used eugenol nanoemulsion loaded with nobiletin as fungistat to study its antifungal activity and potential mechanism of Penicillium italicum (P. italicum). The results showed that the minimum inhibitory concentration (MIC) of eugenol nanoemulsion loaded with nobiletin (EGN) was lower than that of pure eugenol nanoemulsion (EG), which were 160 μg/mL and 320 μg/mL, respectively. At the same time, the mycelial growth inhibition rate of EGN nanoemulsion (54.68 %) was also higher than that of EG nanoemulsion (9.92 %). This indicates that EGN nanoemulsion is more effective than EG nanoemulsion. Compared with EG nanoemulsion, the treatment of EGN nanoemulsion caused more serious damage to the cell structure of P. italicum. At the same time, in vitro inoculation experiments found that EGN nanoemulsion has better control and delay the growth and reproduction of P. italicum in citrus fruits. And the results reflected that EGN nanoemulsion may be considered as potential resouces of natural antiseptic to inhibit blue mold disease of citrus fruits, because it has good antifungal activity.
Topics: Penicillium; Eugenol; Antifungal Agents; Emulsions; Flavones; Citrus; Microbial Sensitivity Tests; Nanoparticles
PubMed: 38823189
DOI: 10.1016/j.ijfoodmicro.2024.110769 -
Applied Microbiology and Biotechnology May 2024The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its... (Review)
Review
The design, development, and obtaining of nanostructured materials, such as polymeric nanoparticles, have garnered interest due to loading therapeutic agents and its broad applicability. Polymeric nanoparticle synthesis employs advanced techniques such as the double emulsion approach and the pH-driven method, allowing the efficient incorporation of active compounds into these matrices. These loading methods ensure compound stability within the polymeric structure and enable control of the release of therapeutic agents. The ability of loaded polymeric nanoparticles to transport and release therapeutic agents on target manner represents a significant advancement in the quest for effective therapeutic solutions. Amid escalating concerns regarding antimicrobial resistance, interventions using polymeric nanostructures stand out for the possibility of carrying antimicrobial agents and enhancing antibacterial action against antibiotic-resistant bacteria, making a new therapeutic approach or complement to conventional treatments. In this sense, the capability of these polymeric nanoparticles to act against Escherichia coli underscores their relevance in controlling bacterial infections. This mini-review provides a comprehensive synthesis of promising techniques for loading therapeutic agents into polymeric nanoparticles highlighting methodologies and their implications, addressing prospects of combating bacterial infections caused by E. coli. KEY POINTS: • The double emulsion method provides control over size and release of bioactives. • The pH-driven method improves the solubility, stability, and release of active. • The methods increase the antibacterial action of those encapsulated in PNPs.
Topics: Anti-Bacterial Agents; Nanoparticles; Hydrogen-Ion Concentration; Emulsions; Polymers; Escherichia coli; Escherichia coli Infections; Biological Products
PubMed: 38819646
DOI: 10.1007/s00253-024-13114-5 -
Journal of Translational Medicine May 2024The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer... (Review)
Review
The intersection of nanotechnology and pharmacology has revolutionized the delivery and efficacy of chemotherapeutic agents, notably docetaxel, a key drug in cancer treatment. Traditionally limited by poor solubility and significant side effects, docetaxel's therapeutic potential has been significantly enhanced through its incorporation into nanoplatforms, such as nanofibers and nanoparticles. This advancement offers targeted delivery, controlled release, and improved bioavailability, dramatically reducing systemic toxicity and enhancing patient outcomes. Nanofibers provide a versatile scaffold for the controlled release of docetaxel, utilizing techniques like electrospinning to tailor drug release profiles. Nanoparticles, on the other hand, enable precise drug delivery to tumor cells, minimizing damage to healthy tissues through sophisticated encapsulation methods such as nanoprecipitation and emulsion. These nanotechnologies not only improve the pharmacokinetic properties of docetaxel but also open new avenues in regenerative medicine by facilitating targeted therapy and cellular regeneration. This narrative review highlights the transformative impact of docetaxel-loaded nanoplatforms in oncology and beyond, showcasing the potential of nanotechnology to overcome the limitations of traditional chemotherapy and pave the way for future innovations in drug delivery and regenerative therapies. Through these advancements, nanotechnology promises a new era of precision medicine, enhancing the efficacy of cancer treatments while minimizing adverse effects.
Topics: Humans; Docetaxel; Regenerative Medicine; Neoplasms; Animals; Nanoparticles; Antineoplastic Agents; Treatment Outcome; Drug Delivery Systems
PubMed: 38816723
DOI: 10.1186/s12967-024-05347-9 -
International Journal of Pharmaceutics May 2024Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label"...
Development and in vitro evaluation of an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) loaded with an amphotericin B-monoacyl phosphatidylcholine complex for oral delivery.
Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label" use of drugs in this particular population. In this study, an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) was developed for oral delivery of a commonly used "off-label" drug - amphotericin B (AmB). AmB was complexed with monoacyl-phosphatidylcholine (MAPC) by lyophilization, transforming crystalline AmB into its amorphous state in the AmB-MAPC complex (APC). The APC-loaded SNEDDS (APC-SNEDDS) showed excellent self-emulsifying properties; after dispersion of the APC-SNEDDS in purified water, nanoscale emulsion droplets were formed within 1 min with a z-average size of 179 ± 1 nm. In vitro pediatric gastrointestinal (GI) digestion and dissolution results showed that the APC-SNEDDS significantly increased the amount of AmB solubilized in aqueous phase and that the precipitated AmB from the APC-SNEDDS re-dissolved faster, compared with crystalline AmB in SNEDDS (AmB-SNEDDS), the complex without the SNEDDS (APC), the physical mixture of AmB and MAPC (AmB/MAPC PM), and crystalline AmB alone (AmB). Overall, the present in vitro results suggest that integrating the APC into an infant friendly SNEDDS is a promising approach for oral delivery of AmB to young pediatric patients.
PubMed: 38815640
DOI: 10.1016/j.ijpharm.2024.124286 -
Phytomedicine : International Journal... Jul 2024Polymyxin E is widely recognized as a last resort for treating multidrug-resistant gram-negative bacteria. Unfortunately, the effectiveness of polymyxin E is...
BACKGROUND
Polymyxin E is widely recognized as a last resort for treating multidrug-resistant gram-negative bacteria. Unfortunately, the effectiveness of polymyxin E is significantly reduced when treating life-threatening bacterial infections due to plasmid-mediated polymyxin E resistance. The synergistic effect of applying a polymyxin E adjuvant is a promising strategy for overcoming the growing threat of antibiotic-resistant pathogens.
PURPOSE
To evaluate the synergistic effect of fisetin and polymyxin E on S. typhimurium infections in vivo and further elucidate the underlying mechanism of this effect.
METHODS
The effect of combining fisetin and polymyxin E to treat mobilized colistin resistance-1-positive (MCR-1-positive) gram-negative bacteria in vitro was examined using various methods, such as checkerboard assays, growth curves and time‒kill curves. To elucidate the mechanism by which fisetin affects MCR-1, we employed ultraviolet (UV) absorption spectroscopy, thin layer chromatography (TLC), and western blot analysis to investigate its effect at the protein level. Subsequently, molecular dynamics simulations (MDS) and metabolomics analysis were utilized to determine the site of interaction between fisetin and MCR-1 as well as the potential pathways and mechanisms involved. A new nanoemulsion of fisetin was produced using high-pressure homogenization, and its stability was tested. Finally, two animal models of S. typhimurium HYM2 infection were established to evaluate the synergistic effect of polymyxin E and fisetin in vivo.
RESULTS
Our study revealed that fisetin exhibited a synergistic effect when combined with polymyxin E against MCR-1-positive S. typhimurium. The TLC results demonstrated that fisetin could inhibit the phosphoethanolamine (PEA) transfer of the MCR-1 protein, thereby restoring the activity of polymyxin E in strains against MCR-1. The MDS analysis indicated robust and immediate binding between fisetin and the MCR-1 protein, with both hydrophobic and polar effects playing significant roles in determining the binding energy of the former. Metabolomic studies demonstrated that the addition of fisetin significantly modulated bacterial metabolites. Moreover, it effectively inhibited the activity of ABC transporters in bacteria, thereby mitigating bacterial drug resistance and enhancing the therapeutic efficacy of polymyxin E. Furthermore, in mouse and chick models of infection, intragastric administration of the fisetin nanoemulsion together with polymyxin E resulted in significant therapeutic benefits, including increased survival rates, reduced bacterial colonization, and decreased levels of inflammatory factors.
CONCLUSION
Fisetin, an MCR-1 inhibitor and a promising synergistic partner of polymyxin E, has significant potential for clinical application in the treatment of S. typhimurium infections, particularly those resulting extensively from drug-resistant MCR-1-positive strains.
Topics: Flavonols; Animals; Colistin; Anti-Bacterial Agents; Salmonella typhimurium; Flavonoids; Emulsions; Drug Synergism; Mice; Microbial Sensitivity Tests; Female; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Molecular Dynamics Simulation; Mice, Inbred BALB C
PubMed: 38815408
DOI: 10.1016/j.phymed.2024.155768 -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly... (Review)
Review
Lipid-based systems, such as self-microemulsifying systems (SMEDDS) are attracting strong attention as a formulation approach to improve the bioavailability of poorly water-soluble drugs. By applying the "spring and parachute" strategy in designing supersaturable SMEDDS, it is possible to maintain the drug in the supersaturated state long enough to allow absorption of the complete dose, thus improving the drug's bio-availability. As such an approach allows the incorporation of larger amounts of the drug in equal or even lower volumes of SMEDDS, it also enables the production of smaller final dosage forms as well as decreased gastrointestinal irritation, being of particular importance when formulating dosage forms for children or the elderly. In this review, the technological approaches used to prolong the drug supersaturation are discussed regarding the type and concentration of polymers used in liquid and solid SMEDDS formulation. The addition of hypromellose derivatives, vinyl polymers, polyethylene glycol, polyoxyethylene, or polymetacrylate copolymers proved to be effective in inhibiting drug precipitation. Regarding the available literature, hypromellose has been the most commonly used polymeric precipitation inhibitor, added in a concentration of 5 % (). However, the inhibiting ability is mainly governed not only by the physicochemical properties of the polymer but also by the API, therefore the choice of optimal precipitation inhibitor is recommended to be evaluated on an individual basis.
Topics: Biological Availability; Humans; Solubility; Emulsions; Lipids; Chemical Precipitation; Pharmaceutical Preparations; Chemistry, Pharmaceutical; Drug Compounding; Polymers; Drug Delivery Systems; Excipients; Animals
PubMed: 38815207
DOI: 10.2478/acph-2024-0023 -
Research (Washington, D.C.) 2024Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted...
Thrombosis can cause life-threatening disorders. Unfortunately, current therapeutic methods for thrombosis using injecting thrombolytic medicines systemically resulted in unexpected bleeding complications. Moreover, the absence of practical imaging tools for thrombi raised dangers of undertreatment and overtreatment. This study develops a theranostic drug carrier, Pkr(IR-Ca/Pda-uPA)-cRGD, that enables real-time monitoring of the targeted thrombolytic process of deep vein thrombosis (DVT). Pkr(IR-Ca/Pda-uPA)-cRGD, which is prepared from a Pickering-emulsion-like system, encapsulates both near-infrared-II (NIR-II) contrast agent (IR-1048 dye, loading capacity: 28%) and urokinase plasminogen activators (uPAs, encapsulation efficiency: 89%), pioneering the loading of multiple drugs with contrasting hydrophilicity into one single-drug carrier. Upon intravenous injection, Pkr(IR-Ca/Pda-uPA)-cRGD considerably targets to thrombi selectively (targeting rate: 91%) and disintegrates in response to acidic thrombi to release IR-1048 dye and uPA for imaging and thrombolysis, respectively. Investigations indicate that Pkr(IR-Ca/Pda-uPA)-cRGD enabled real-time visualization of targeted thrombolysis using NIR-II imaging in DVT models, in which thrombi were eliminated (120 min after drug injection) without bleeding complications. This may be the first study using convenient NIR-II imaging for real-time visualization of targeted thrombolysis. It represents the precision medicine that enables rapid response to acquire instantaneous medical images and make necessary real-time adjustments to diagnostic and therapeutic protocols during treatment.
PubMed: 38812529
DOI: 10.34133/research.0388