Codelivery of ivermectin and methyl dihydrojasmonate in nanostructured lipid carrier for synergistic antileukemia therapy.

Chronic myeloid leukemia is a life-threatening blood-cancer prevalent among children and adolescents. Research for innovative therapeutics combine drug-repurposing, phytotherapeutics and nanodrug-delivery. Ivermectin (Ivn) is a potent anthelmintic, repurposed for antileukemic-activity. However, Ivn exerts off-target toxicity. Methyl-dihydrojasmonate (MJ) is a phytochemical of known antileukemic potential. Herein, we developed for the first-time Ivn/MJ-coloaded nanostructured-lipid-carrier (Ivn@MJ-NLC) for leveraging the antileukemic-activity of the novel Ivn/MJ-combination while ameliorating possible adverse-effects. The developed Ivn@MJ-NLC possessed optimum-nanosize (97 ± 12.70 nm), PDI (0.33 ± 0.02), entrapment for Ivn (97.48 ± 1.48 %) and MJ (99.48 ± 0.57 %) and controlled-release of Ivn (83 % after 140 h) and MJ (80.98 ± 2.45 % after 48 h). In-vitro K562 studies verified Ivn@MJ-NLC prominent cytotoxicity (IC50 = 35.01 ± 2.23 µg/mL) with pronounced Ivn/MJ-synergism (combination-index = 0.59) at low-concentrations (5-10 µg/mL Ivn). Superior Ivn@MJ-NLC cytocompatibility was established on oral-epithelial-cells (OEC) with high OEC/K562 viability-ratio (1.49-1.85). The innovative Ivn@MJ-NLC enhanced K562-nuclear-fragmentation and afforded upregulation of caspase-3 and BAX (1.71 ± 0.07 and 1.45 ± 0.07-fold-increase, respectively) compared to control. Ex-vivo hemocompatibility and in-vivo-biocompatibility of parenteral-Ivn@MJ-NLC, compared to Ivn-solution, was verified via biochemical-blood analysis, histological and histomorphometric studies of liver and kidney tissues. Our findings highlight Ivn@MJ-NLC as an Ivn/MJ synergistic antileukemic platform, ameliorating possible adverse-effects.

Innovative approaches to Alzheimer's therapy: Harnessing the power of heterocycles, oxidative stress management, and nanomaterial drug delivery system.

Alzheimer's disease (AD) presents a complex pathology involving amyloidogenic proteolysis, neuroinflammation, mitochondrial dysfunction, and cholinergic deficits. Oxidative stress exacerbates AD progression through pathways like macromolecular peroxidation, mitochondrial dysfunction, and metal ion redox potential alteration linked to amyloid-beta (Aß). Despite limited approved medications, heterocyclic compounds have emerged as promising candidates in AD drug discovery. This review highlights recent advancements in synthetic heterocyclic compounds targeting oxidative stress, mitochondrial dysfunction, and neuroinflammation in AD. Additionally, it explores the potential of nanomaterial-based drug delivery systems to overcome challenges in AD treatment. Nanoparticles with heterocyclic scaffolds, like polysorbate 80-coated PLGA and Resveratrol-loaded nano-selenium, show improved brain transport and efficacy. Micellar CAPE and Melatonin-loaded nano-capsules exhibit enhanced antioxidant properties, while a tetra hydroacridine derivative (CHDA) combined with nano-radiogold particles demonstrates promising acetylcholinesterase inhibition without toxicity. This comprehensive review underscores the potential of nanotechnology-driven drug delivery for optimizing the therapeutic outcomes of novel synthetic heterocyclic compounds in AD management. Furthermore, the inclusion of various promising heterocyclic compounds with detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) data provides valuable insights for planning the development of novel drug delivery treatments for AD.

Advances in local drug delivery technologies for improved rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by an inflammatory microenvironment and cartilage erosion within the joint cavity. Currently, antirheumatic agents yield significant outcomes in RA treatment. However, their systemic administration is limited by inadequate drug retention in lesion areas and non-specific tissue distribution, reducing efficacy and increasing risks such as infection due to systemic immunosuppression. Development in local drug delivery technologies, such as nanostructure-based and scaffold-assisted delivery platforms, facilitate enhanced drug accumulation at the target site, controlled drug release, extended duration of the drug action, reduced both dosage and administration frequency, and ultimately improve therapeutic outcomes with minimized damage to healthy tissues. In this review, we introduced pathogenesis and clinically used therapeutic agents for RA, comprehensively summarized locally administered nanostructure-based and scaffold-assisted drug delivery systems, aiming at improving the therapeutic efficiency of RA by alleviating the inflammatory response, preventing bone erosion and promoting cartilage regeneration. In addition, the challenges and future prospects of local delivery for clinical translation in RA are discussed.

Tobramycin-mediated self-assembly of DNA nanostructures for targeted treatment of Pseudomonas aeruginosa-infected lung inflammation.

Pseudomonas aeruginosa (PA) is one of the most common multidrug-resistant pathogens found in clinics, often manifesting as biofilms. However, due to the emergence of superbugs in hospitals and the overuse of antibiotics, the prevention and treatment of PA infections have become increasingly challenging. Utilizing DNA nanostructures for packaging and delivering antibiotics presents an intervention strategy with significant potential. Nevertheless, construction of functional DNA nanostructures with multiple functionalities and enhanced stability in physiological settings remains challenging. In this study, the authors propose a magnesium-free assembly method that utilizes tobramycin (Tob) as a mediator to assemble DNA nanostructures, allowing for the functionalization of DNA nanostructures by combining DNA and antibiotics. Additionally, our study incorporates maleimide-modified DNA into the nanostructures to act as a targeting moiety specifically directed towards the pili of PA. The targeting ability of the constructed functional DNA nanostructure significantly improves the local concentration of Tob, thereby reducing the side effects of antibiotics. Our results demonstrate the successful construction of a maleimide-decorated Tob/DNA nanotube (NTTob-Mal) for the treatment of PA-infected lung inflammation. The stability and biocompatibility of NTTob-Mal are confirmed, highlighting its potential for clinical applications. Furthermore, its specificity in recognizing and adhering to PA has been validated. In vitro experiments have shown its efficacy in inhibiting PA biofilm formation, and in a murine model, NTTob-Mal has exhibited significant therapeutic effectiveness against PA-induced pneumonia. In summary, the proposed antibiotic drug-mediated DNA nanostructure assembly approach holds promise as a novel strategy for targeted treatment of PA infections.

Biomedical applications of nanomaterials in the advancement of nucleic acid therapy: Mechanistic challenges, delivery strategies, and therapeutic applications.

In the past few decades, substantial advancement has been made in nucleic acid (NA)-based therapies. Promising treatments include mRNA, siRNA, miRNA, and anti-sense DNA for treating various clinical disorders by modifying the expression of DNA or RNA. However, their effectiveness is limited due to their concentrated negative charge, instability, large size, and host barriers, which make widespread application difficult. The effective delivery of these medicines requires safe vectors that are efficient & selective while having non-pathogenic qualities; thus, nanomaterials have become an attractive option with promising possibilities despite some potential setbacks. Nanomaterials possess ideal characteristics, allowing them to be tuned into functional bio-entity capable of targeted delivery. In this review, current breakthroughs in the non-viral strategy of delivering NAs are discussed with the goal of overcoming challenges that would otherwise be experienced by therapeutics. It offers insight into a wide variety of existing NA-based therapeutic modalities and techniques. In addition to this, it provides a rationale for the use of non-viral vectors and a variety of nanomaterials to accomplish efficient gene therapy. Further, it discusses the potential for biomedical application of nanomaterials-based gene therapy in various conditions, such as cancer therapy, tissue engineering, neurological disorders, and infections.

Safety and Biodistribution of Nanoligomers Targeting the SARS-CoV-2 Genome for the Treatment of COVID-19.

As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.

Enhancement of Gene Editing and Base Editing with Therapeutic Ribonucleoproteins through In Vivo Delivery Based on Absorptive Silica Nanoconstruct.

Key to the widespread and secure application of genome editing tools is the safe and effective delivery of multiple components of ribonucleoproteins (RNPs) into single cells, which remains a biological barrier to their clinical application. To overcome this issue, a robust RNP delivery platform based on a biocompatible sponge-like silica nanoconstruct (SN) for storing and directly delivering therapeutic RNPs, including Cas9 nuclease RNP (Cas9-RNP) and base editor RNP (BE-RNP) is designed. Compared with commercialized material such as lipid-based methods, up to 50-fold gene deletion and 10-fold base substitution efficiency is obtained with a low off-target efficiency by targeting various cells and genes. In particular, gene correction is successfully induced by SN-based delivery through intravenous injection in an in vivo solid-tumor model and through subretinal injection in mouse eye. Moreover, because of its low toxicity and high biodegradability, SN has negligible effect on cellular function of organs. As the engineered SN can overcome practical challenges associated with therapeutic RNP application, it is strongly expected this platform to be a modular RNPs delivery system, facilitating in vivo gene deletion and editing.

OncoTherad® (MRB-CFI-1) nano-immunotherapy reduced tumoral progression in non-muscle invasive bladder cancer through activation of Toll-like signaling pathway.

The new modalities for treating patients with high-grade non-muscle invasive bladder cancer (HGNMIBC) for whom Bacillus Calmette-Guerin (BCG) has failed or is contraindicated are recently increasing due to the development of new drugs. Since NMIBC is sensitive to immunotherapy, Toll-like receptors (TLRs) agonist compounds may represent a potential antitumor therapeutic approach. Our research group developed a synthetic compound, with antitumor and immunological properties, called OncoTherad® (MRB-CFI-1). To evaluate the effects of OncoTherad® (MRB-CFI-1) and its compounds (P14-16 and CFI-1), thirty-six female C57Bl/6 J mice were divided into six groups (n = 6): Control, Cancer, Cancer + BCG (40 mg), Cancer + OncoTherad® (20 mg/mL), Cancer + P14-16 (20 mg/mL) and Cancer + CFI-1 (20 mg/mL). NMIBC was chemically induced (N-ethyl-N-nitrosourea 50 mg/mL) and the treatments were followed for six weeks. The bladder was collected and routinely processed for immunohistochemical analyses of the Toll-Like receptors signaling pathway (TLR2, TLR4, MyD88, IRF-3, IKK-α, NF-kB, TNF-α, TRIF, IFN-γ, IL-6). The results obtained showed that the tumor progression was 100 % reduced on OncoTherad® (MRB-CFI-1) treated animals. Immunohistochemical analysis demonstrated that while the conventional BCG treatment stimulated the canonic pathway, OncoTherad® (MRB-CFI-1) stimulated the non-canonical pathway (increasing expression of TLR4, TRIF, IRF, and IFNγ). OncoTherad® (MRB-CFI-1) could be considered a promising therapy in the treatment of NMIBC.

Metal oxide nanocage as drug delivery systems for Favipiravir, as an effective drug for the treatment of COVID-19: a computational study.

This paper is a summary of research that looks at the potential of fullerene-like (MO)12 nanoclusters (NCs) in drug-carrying systems using density functional theory. Favipiravir/Zn12O12 (- 34.80 kcal/mol), Favipiravir/Mg12O12 (- 34.98 kcal/mol), and Favipiravir/Be12O12 (- 30.22 kcal/mol) were rated in order of drug adsorption degrees. As a result, Favipiravir attachment to (MgO)12 and (ZnO)12 might be simple, increasing Favipiravir loading efficiency. In addition, the quantum theory of atoms in molecules (QTAIM) assessment was utilized to look at the interactions between molecules. The FMO, ESP, NBO, and Eads reactivity patterns were shown to be in excellent agreement with the QTAIM data. The electrostatic properties of the system with the biggest positive charge on the M atom and the largest Eads were shown to be the best. This system was shown to be the best attraction site for nucleophilic agents. The findings show that (MgO)12 and (ZnO)12 have great carrier potential and may be used in medication delivery.

Efficacy of NHP66 Bioactive Cage on Patients with Cervical Spine Injury in Short-Track Speed Skating.

BACKGROUND: Short-track speed skating (STSS) is an extreme sport in pursuit of extreme speed and explosive force. In such a sport, once athletes fall down, they are susceptible to serious cervical spine injury (CSI) under the inertia of high-velocity movement. Nanohydroxyapatite/polyamide 66 (NHP66) bioactive cage is a high-tech product of nanotechnology in the medical field in recent years. With a structure similar to that of human cortical bone, NHP66 bioactive cage has extremely high toughness and strength, which tailors to the needs of STSS. OBJECTIVE: This study mainly analyzed the therapeutic effect of NHP66 on patients with CSI in STSS, aiming to provide new opportunities for the treatment of this patient population. METHODS: A total of 51 patients with CSI treated in our hospital were enrolled, including 19 cases of short-track speed skaters (observation group) and 32 cases of car accidents, falls from heights, or collision injuries (control group). The relevant surgical indicators (operation time, intraoperative blood loss, etc.), the incidence of adverse reactions, the Cobb angle of cervical lordosis before and after surgery, and the fusion segment height of the cage were observed and compared between the two groups. Postoperative pain was evaluated by the visual analog scale (VAS), improvement of spinal cord injury was assessed by the American Spinal Cord Injury Association (ASIA) Impairment Scale, and bone fusion, bone subsidence, and other motor functions were assessed by the Japanese Orthopaedic Association (JOA) score rating system. RESULTS: The operation time, intraoperative blood loss, and incidence of adverse reactions in the observation group were significantly lower than those in the control group. The Cobb angle of cervical lordosis and the fusion segment height of cage increased significantly higher in both groups after surgery. In addition, the VAS scores of the observation group 2 h and 3 d after operation were significantly lower than those of the control group. In terms of improvement of spinal cord injury, ASIA and JOA scores in the observation group were significantly higher than those before treatment and in the control group. There was no significant difference in bone fusion activity between the two groups. CONCLUSIONS: In this study, it is found through experiments that NHP66 has higher safety and application value than autogenous iliac bone, confirming that NHP66 can achieve significant results as a cage for anterior cervical decompression and iliac bone graft fusion and internal fixation in short-track speed skaters after CSI.

Controlled decoration of nanoceria on the surface of MoS2nanoflowers to improve the biodegradability and biocompatibility inDrosophila melanogastermodel.

In recent years, nanozymes based on two-dimensional (2D) nanomaterials have been receiving great interest for cancer photothermal therapy. 2D materials decorated with nanoparticles (NPs) on their surface are advantageous over conventional NPs and 2D material based systems because of their ability to synergistically improve the unique properties of both NPs and 2D materials. In this work, we report a nanozyme based on flower-like MoS2nanoflakes (NFs) by decorating their flower petals with NCeO2using polyethylenimine (PEI) as a linker molecule. A detailed investigation on toxicity, biocompatibility and degradation behavior of fabricated nanozymes in wild-typeDrosophila melanogastermodel revealed that there were no significant effects on the larval size, morphology, larval length, breadth and no time delay in changing larvae to the third instar stage at 7-10 d for MoS2NFs before and after NCeO2decoration. The muscle contraction and locomotion behavior of third instar larvae exhibited high distance coverage for NCeO2decorated MoS2NFs when compared to bare MoS2NFs and control groups. Notably, the MoS2and NCeO2-PEI-MoS2NFs treated groups at 100µg ml-1covered a distance of 38.2 mm (19.4% increase when compared with control) and 49.88 mm (no change when compared with control), respectively. High-resolution transmission electron microscopy investigations on the new born fly gut showed that the NCeO2decoration improved the degradation rate of MoS2NFs. Hence, nanozymes reported here have huge potential in various fields ranging from biosensing, cancer therapy and theranostics to tissue engineering and the treatment of Alzheimer's disease and retinal therapy.

Nanotechnology-Abetted Astaxanthin Formulations in Multimodel Therapeutic and Biomedical Applications.

Astaxanthin (AXT) is one of the most important fat-soluble carotenoids that have abundant and diverse therapeutic applications namely in liver disease, cardiovascular disease, cancer treatment, protection of the nervous system, protection of the skin and eyes against UV radiation, and boosting the immune system. However, due to its intrinsic reactivity, it is chemically unstable, and therefore, the design and production processes for this compound need to be precisely formulated. Nanoencapsulation is widely applied to protect AXT against degradation during digestion and storage, thus improving its physicochemical properties and therapeutic effects. Nanocarriers are delivery systems with many advantages─ease of surface modification, biocompatibility, and targeted drug delivery and release. This review discusses the technological advancement in nanocarriers for the delivery of AXT through the brain, eyes, and skin, with emphasis on the benefits, limitations, and efficiency in practice.

Melittin and diclofenac synergistically promote wound healing in a pathway involving TGF-ß1.

A dysregulation of the wound healing process can lead to the development of various intractable ulcers or excessive scar formation. Therefore it is essential to identify novel pharmacological strategies to promote wound healing and restore the mechanical integrity of injured tissue. The goal of the present study was to formulate a nano-complex containing melittin (MEL) and diclofenac (DCL) with the aim to evaluate their synergism and preclinical efficacy in an in vivo model of acute wound. After its preparation and characterization, the therapeutic potential of the combined nano-complexes was evaluated. MEL-DCL nano-complexes exhibited better regenerated epithelium, keratinization, epidermal proliferation, and granulation tissue formation, which in turn showed better wound healing activity compared to MEL, DCL, or positive control. The nano-complexes also showed significantly enhanced antioxidant activity. Treatment of wounded skin with MEL-DCL nano-complexes showed significant reduction of interleukin-6 (IL-6), IL-1ß, and tumor necrosis factor-α (TNF-α) pro-inflammatory markers that was paralleled by a substantial increase in mRNA expression levels of collagen, type I, alpha 1 (Col1A1) and collagen, type IV, alpha 1 (Col4A1), and hydroxyproline content as compared to individual drugs. Additionally, MEL-DCL nano-complexes were able to significantly increase hypoxia-inducible factor 1-alpha (HIF-1α) and transforming growth factor beta 1 (TGF-ß1) proteins expression compared to single drugs or negative control group. SB431542, a selective inhibitor of type-1 TGF-ß receptor, significantly prevented in our in vitro assay the wound healing process induced by the MEL-DCL nano-complexes, suggesting a key role of TGF-ß1 in the wound closure. In conclusion, the nano-complex of MEL-DCL represents a novel pharmacological tool that can be topically applied to improve wound healing.

Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy.

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of ·OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Evaluation of wound healing potential and biochemical estimation of sage oil nanoemulsion on animal model.

The study was aimed to design a nano emulsion formulations of Sage oil and to determine its effectiveness in healing the wound using rats as a model. Sage oil nanoemulsion (o/w) was formulated by a spontaneous emulsification method and tested for physicochemical parameters. The wound creation methods namely; circular excision and linear incision were utilized in the present study. Many specifications like tensile strength, DNA, total protein, Hexosamine and Uronic acid, were estimated from the tissues collected from incised wounds. The antioxidant and antimicrobial activity of the oil was estimated from the wound tissue homogenate. Finally epithelialization period and concentration of TNF-α were also measured. A Significant rise in collagen content by 77.52% and tensile strength by 56.20% were noticed in comparison to control. Reduction in period of epithelialization was noticed by 42.85% in comparison to control. The treatment groups confirmed significant antimicrobial activity in comparison to control. It was evident from the results that Sage oil nano emulsion could be the accelerator in wound healing process and it may be devoid of other drawbacks which would be possible with synthetic drug.

Surfactant Proteins A/D-CD14 on Alveolar Macrophages Is a Common Pathway Associated With Phagocytosis of Nanomaterials and Cytokine Production.

Alveolar macrophages are responsible for clearance of airborne dust and pathogens. How they recognize and phagocytose a variety of engineered nanomaterials (ENMs) with different properties is an important issue for safety assessment of ENMs. Surfactant-associated proteins, specifically existing in the pulmonary surfactant, are important opsonins for phagocytosis of airborne microorganisms. The purposes of the current study are to understand whether opsonization of ENMs by surfactant-associated proteins promotes phagocytosis of ENMs and cytokine production, and to determine whether a common pathway for phagocytosis of ENMs with different properties exists. For these purposes, four ENMs, MWCNT-7, TiO2, SiO2, and fullerene C60, with different shapes, sizes, chemical compositions, and surface reactivities, were chosen for this study. Short-term pulmonary exposure to MWCNT-7, TiO2, SiO2, and C60 induced inflammation in the rat lung, and most of the administered ENMs were phagocytosed by alveolar macrophages. The ENMs were phagocytosed by isolated primary alveolar macrophages (PAMs) in vitro, and phagocytosis was enhanced by rat bronchioalveolar lavage fluid (BALF), suggesting that proteins in the BALF were associated with phagocytosis. Analysis of proteins bound to the 4 ENMs by LC/MS indicated that surfactant-associated proteins A and D (SP-A, SP-D) were common binding proteins for all the 4 ENMs. Both BALF and SP-A, but not SP-D, enhanced TNF-α production by MWCNT-7 treated PAMs; BALF, SP-A, and SP-D increased IL-1ß production in TiO2 and SiO2 treated PAMs; and BALF, SP-A, and SP-D enhanced IL-6 production in C60 treated PAMs. Knockdown of CD14, a receptor for SP-A/D, significantly reduced phagocytosis of ENMs and SP-A-enhanced cytokine production by PAMs. These results indicate that SP-A/D can opsonize all the test ENMs and enhance phagocytosis of the ENMs by alveolar macrophages through CD14, suggesting that SP-A/D-CD14 is a common pathway mediating phagocytosis of ENMs. Cytokine production induced by ENMs, however, is dependent on the type of ENM that is phagocytosed. Our results demonstrate a dual role for surfactant proteins as opsonins for both microbes and for inhaled dusts and fibers, including ENMs, allowing macrophages to recognize and remove the vast majority of these particles, thereby, greatly lessening their toxicity in the lung.

A pre-formulation study of tetracaine loaded in optimized nanostructured lipid carriers.

Tetracaine (TTC) is a local anesthetic broadly used for topical and spinal blockade, despite its systemic toxicity. Encapsulation in nanostructured lipid carriers (NLC) may prolong TTC delivery at the site of injection, reducing such toxicity. This work reports the development of NLC loading 4% TTC. Structural properties and encapsulation efficiency (%EE > 63%) guided the selection of three pre-formulations of different lipid composition, through a 23 factorial design of experiments (DOE). DLS and TEM analyses revealed average sizes (193-220 nm), polydispersity (< 0.2), zeta potential |- 21.8 to - 30.1 mV| and spherical shape of the nanoparticles, while FTIR-ATR, NTA, DSC, XRD and SANS provided details on their structure and physicochemical stability over time. Interestingly, one optimized pre-formulation (CP-TRANS/TTC) showed phase-separation after 4 months, as predicted by Raman imaging that detected lack of miscibility between its solid (cetyl palmitate) and liquid (Transcutol) lipids. SANS analyses identified lamellar arrangements inside such nanoparticles, the thickness of the lamellae been decreased by TTC. As a result of this combined approach (DOE and biophysical techniques) two optimized pre-formulations were rationally selected, both with great potential as drug delivery systems, extending the release of the anesthetic (> 48 h) and reducing TTC cytotoxicity against Balb/c 3T3 cells.

Development of Coriandrum sativum Oil Nanoemulgel and Evaluation of Its Antimicrobial and Anticancer Activity.

This study is aimed at developing coriander oil into a nanoemulgel and evaluating its antimicrobial and anticancer effects. Coriander (Coriandrum sativum) oil was developed into a nanoemulgel by using a self-nanoemulsifying technique with Tween 80 and Span 80. Hydrogel material (Carbopol 940) was then incorporated into the nanoemulsion and mixed well. After this, we evaluated the particle size, polydispersity index (PDI), rheology, antimicrobial effect, and cytotoxic activity. The nanoemulsion had a PDI of 0.188 and a particle size of 165.72 nm. Interesting results were obtained with the nanoemulgel against different types of bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 2.3 µg/ml, 3.75 µg/ml, and 6.5 µg/ml, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the nanoemulgel when applying it to human breast cancer cells (MCF-7), hepatocellular carcinoma cells (Hep3B), and human cervical epithelioid carcinoma cells (HeLa) was 28.84 µg/ml, 28.18 µg/ml, and 24.54 µg/ml, respectively, which proves that the nanoemulgel has anticancer effects. The development of C. sativum oil into a nanoemulgel by using a self-nanoemulsifying technique showed a bioactive property better than that in crude oil. Therefore, simple nanotechnology techniques are a promising step in the preparation of pharmaceutical dosage forms.

Robust hemostatic bandages based on nanoclay electrospun membranes.

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.

The Effect of Zbxz23ir-21 NANO(nanomaterials) Delivery Vector on Apoptosis and PTEN(phosphatase and tensin homolog deleted on chromosome ten)/PI3K(Intracellular phosphatidylinositol kinase)/AKT(related to the A and C kinase) in Children with CHOLESTEATOMA in Middle Ear.

Cholesteatoma of the middle ear is a kind of cystic disease with clear boundary formed by the abnormal growth of keratosquamous epithelium in temporal bone. Cholesteatoma otitis caused by it is a common disease in otorhinolaryngology. The EPR effect promotes the selective distribution of macromolecular substances in tumor tissues, which can increase drug efficacy. The purpose of this paper is to prepare and deliver the mir34a small molecule regulator, rubine, by nanotechnology, and to deliver it to the cells successfully. It can passively target tumor tissue through EPR effect, and play its regulatory role on miR-34a, thus inhibiting the growth of cholesteatoma cells. The effects of nano delivery on apoptosis and PIEN/P13K/AKt of children with middle ear choledochoma were tested in this paper. The experimental results were conducted on cholesteatoma cells as cell lines and balb/c nude mice as experimental objects. The expression of PTEN/PI3K/AKT in experimental group and control group was detected by immunohistochemistry. Apoptosis was discussed by cell activity detection. The physical and chemical properties, encapsulation efficiency, drug release ability in vitro and antitumor activity of nanoparticles in vitro and in vivo were studied. The results of cell level experiments in vitro showed that free RUBINE caused about 15% apoptosis, which was not different from RC NPs. The results showed that the nanoparticles could improve the expression of miR-34 in the cells, and then regulate the expression of Bcl-2, Cdk6 and CyclinD1, and play the inhibitory effect of miR-34a on the proliferation and migration of tumor cells.