Free-standing carboxymethyl cellulose film incorporating nanoformulated pomegranate extract for meat packaging.

This study aimed to explore an innovative approach to enhancing the shelf-life and quality of meat products through the application of an active packaging system. The study involved the development of new free-standing carboxymethyl cellulose (CMC) nanocomposite films incorporated with nanoencapsulated flavonoids derived from pomegranate extract. The loaded flavonoids, known for their antioxidant and antimicrobial properties, were nanoencapsulated via a self-assembly approach in a mixture of chitosan and sodium alginate to improve their stability, solubility, and controlled release characteristics. Chemical structure, size, and morphology of the obtained nanoparticles (Pg-NPs) were studied with FTIR, zeta-sizer, and TEM. The Pg-NPs showed particle size of 232 nm, and zeta-potential of -20.7 mV. Various free-standing nanocomposite films were then developed via incorporation of Pg-NPs into CMC-casted films. FTIR, SEM, thermal and mechanical properties, and surface wettability were intensively studied for the nanocomposite films. Barrier properties against water vapor were investigated at 2022 g·m-2d-1. The nanocomposite films possessed superior properties for inhibiting bacterial growth and extending the shelf-life of beef and poultry meat for 12 days compared with the Pg-NPs-free CMC films. This study presented a promising approach for development of active packaging systems with improved antimicrobial and antioxidant properties, and economic and environmental impacts.

In vivo testing of novel nitric oxide-releasing nanoparticles for alleviating heart failure using the zebrafish embryo model.

Heart failure (HF) is a multifactorial, heterogeneous systemic disease that is considered one of the leading causes of death and morbidity worldwide. It is well-known that endothelial dysfunction (ED) plays an important role in cardiac disease etiology. A reduction in the bioavailability of nitric oxide (NO) in the bloodstream leads to vasoconstriction and ED. Many studies indicated diminishment of peripheral arteries vasodilation that is mediated by the endothelium in the of patients with chronic HF. With the advancement of nanomedicine, nanotechnology can provide adequate solutions for delivering exogenous NO with the aid of nanoparticles (NPs) to treat ED. The properties of superparamagnetic iron oxide nanoparticles (SPIONs) enable both passive and active delivery of drugs. This prompted us to investigate the efficacy of our newly-developed hydrogel nanoparticles (NO-RPs) for the delivery and sustained release of NO gas to alleviate cardiac failure and inflammation in the heart failure zebrafish model. The hydrogel NO-RPs incorporate SPIONS and NO precursor. The sustainend release of NO in the NO-RPs (4200 s), overcomes the problem of the short half life of NO in vivo which is expected to ameliorate the reduced NO bioavailabilty, and its consequences in endothelial and cardiac dysfunction. Zebrafish embryos were used as the animal model in this study to determine the effect of SPIONs-loaded NO-RPs on the cardiovascular system. Cardiac failure was induced in 24hpf embryos by exposure to aristolochic acid (AA)(0.25, 0.5 µM) for 8 h, followed by the SPIONs-loaded NO-RPs (0.25, 0.5 mg/ml) for 48 h, experimental groups included: control group which is healthy non treated zebrafish embryos, AA injured zebrafish embryos (HF) model,and NO-RP treated HF zebrafish embryos. Survival rate was assessed at 72hpf. Cardiac function was also evaluated by analyzing cardiac parameters including heartbeat, major blood vessels primordial cardinal vein and dorsal aorta (PCV &DA) diameter, blood flow velocity in PCV & DA vessels, cardiac output, and PCV & DA shear stresses. All cardiac parameters were analyzed with the aid of MicroZebraLab blood flow analysis software from Viewpoint. In addition, we studied the molecular effects of the developed NO-RPs on the mRNA expression of selected pro-inflammatory markers: IL-6, and Cox-2. Our findings demonstrated that the NO-RPs improved the survival rate in the heart failure zebrafish model and reversed heart failure by enhancing blood flow perfusion in Zebrafish embryos, significantly. In addition, RT-PCR results showed that the NO-RPs significantly reduced the expression of pro-inflammatory markers (lL-6&COX-2) in the heart failure zebrafish model. Our study confirmed that the developed SPIONs-loaded NO-RPs are effective tool to alleviate cardiac failure and inflammation in the HF zebrafish model.

Potential anticancer effect of free and nanoformulated Deferasirox for breast cancer treatment: in-vitro and in-vivo evaluation.

BACKGROUND: Breast cancer (BC) stands as the second-leading cause of mortality among women worldwide. Many chemotherapeutic treatments for BC come with significant adverse effects. Additionally, BC is recognized as one of the most resistant forms of malignancy to treatment. Consequently, there exists a critical need for innovative therapeutic agents that are both highly effective and exhibit reduced toxicity and side effects for patients. Deferasirox (DFX), an iron-chelating drug approved by the FDA for oral use, emerges as a promising contender in the fight against BC proliferation. DFX, primarily administered orally, is utilized to address chronic iron excess resulting from blood transfusions, and it is the inaugural treatment for chronic iron overload syndrome. However, DFX encounters limitations due to its poor water solubility. AIM: This study aimed at incorporating DFX into lipid nanocapsules (DFX-LNCs) followed by investigating the anticancer effect of the DFX nanoform as compared to free DFX in-vitro and on an orthotopic BC mouse model in-vivo. METHODS: The DFX-LNCs was prepared and imaged using TEM and also characterized in terms of particle size (PS), zeta potential (ZP), and polydispersity index (PDI) using DLS. Moreover, drug release, cytotoxicity, and anticancer effect were assessed in-vitro, and in-vivo. RESULTS: The results revealed that DFX-LNCs are more cytotoxic than free DFX with IC50 of 4.417 µg/ml and 16.114 µg/ml, respectively, while the plain LNCs didn't show any cytotoxic effect on the 4T1 cell line (IC50 = 122.797 µg/ml). Besides, the apoptotic effect of DFX-LNCs was more pronounced than that of free DFX, as evidenced by Annexin V/PI staining, increased BAX expression, and decreased expression of BcL-2. Moreover, DFX-LNCs showed a superior antitumor effect in-vivo with potent antioxidant and anti-proliferative effects. CONCLUSION: The newly developed DFX nanoform demonstrated a high potential as a promising therapeutic agent for BC treatment.

Triple-layered platform utilizing electrospun nanofibers and 3D-printed sodium alginate-based hydrogel for effective topical treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA), an autoimmune disease impacting the joints, significantly diminishes the quality of life for patients. Conventional treatments predominantly rely on oral or injectable formulations, underscoring the crucial need for an effective topical remedy. The present study reports a novel triple-layered transdermal platform for efficient RA treatment. The patches are based on an electrospun/electrosprayed diclofenac (DIC)-conjugated polyvinyl alcohol (PVA) nanofibers/nanoparticles (NFs/NPs) composite layer sandwiched between an electrospun supporting layer of polycaprolactone (PCL) NFs, and a 3D-printed sodium alginate-based hydrogel (HG) layer incorporating sodium hyaluronate (HA) and rosuvastatin (ROS)-loaded core-shell lipid nanocapsules (LNCs). The ingeniously designed transdermal patches release the chemically conjugated DIC via skin-secreted esterases at the inflamed sites. The LNCs and patches were characterized using DLS, FTIR, DSC, and electron microscopy. ROS-loaded LNCs (<50 nm as per the TEM micrographs) were able to release about 97 % of ROS during 5 days. In-vitro and in-vivo evaluations definitively established the efficacy of the developed platform, showcasing a substantial reduction in IL-6 and TNF-α through sandwich ELISA measurements in cell culture and Rattus norvegicus plasma samples. Besides, the stained photomicrographs of the rats' ankle joints confirmed the alleviation of the RA symptoms via reducing cell infiltration with a preserved joint tissue structure.

Exogenous and endogenous nitric oxide eluting polylactic acid-based nanofibrous scaffolds for enhancing angiogenesis of diabetic wounds.

Delayed wound healing is a major complication that diabetic patients suffer from due to high microbial infection susceptibility, high diabetic wound alkalinity, a low lymphangiogenesis rate, and a high inflammation rate, resulting in severe gangrene. Hence, this study aims to develop a multifunctional adhesive nanofibrous patch to promote the wound healing process. Phenytoin, sildenafil citrate, and/or nitric oxide-eluting nanoparticles were incorporated separately within the polylactic acid nanofibrous layer. Polylactic acid was fabricated in the form of highly porous nanofibrous matrices that resemble the natural structure of skin tissues in order to act as scaffolds that help cell migration and proliferation. A polylactic acid nanofibrous layer incorporating phenytoin was designed to stimulate fibroblast proliferation and inhibit inflammation. Another polylactic acid nanofibrous layer was loaded either with nitric oxide-eluting nanoparticles or sildenafil as a pro-angiogenic layer that can supply tissues with nitric oxide gas either exogenously or endogenously, respectively. The developed nanofibrous layers were in-vitro evaluated through different physicochemical, mechanical, and biological approaches. Finally, the efficiency of the prepared single multilayered patch was tested using an in-vivo alloxan-induced diabetic rats' model, which proved that the patches were able to release the incorporated cargos in a controlled manner, enhancing the wound healing process.

A comprehensive review on lipid nanocarrier systems for cancer treatment: fabrication, future prospects and clinical trials.

Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research.

In-vitro and in-vivo assessment of pH-responsive core-shell nanocarrier system for sequential delivery of methotrexate and 5-fluorouracil for the treatment of breast cancer.

Breast cancer (BC) is one of the leading fatal diseases affecting females worldwide. Despite the presence of tremendous chemotherapeutic agents, the resistance emergence directs the recent research towards synergistic drugs' combination along with encapsulation inside biocompatible smart nanocarriers. Methotrexate (MTX) and 5-fluorouracil (Fu) are effective against BC and have sequential synergistic activity. In this study, a core-shell nanocarrier composed of mesoporous silica nanoparticles (MSN) as the core and zeolitic imidazolate framework-8 nano metal organic frameworks (ZIF-8 NMOF) as the shell was developed and loaded with Fu and MTX, respectively. The developed nanostructure; Fu-MSN@MTX-NMOF was validated by several characterization techniques and conferred high drugs' entrapment efficiency (EE%). In-vitro assessment revealed a pH-responsive drug release pattern in the acidic pH where MTX was released followed by Fu. The cytotoxicity evaluation indicated enhanced anticancer effect of the Fu-MSN@MTX-NMOF relative to the free drugs in addition to time-dependent fortified cytotoxic effect due to the sequential drugs' release. The in-vivo anticancer efficiency was examined using Ehrlich ascites carcinoma (EAC) animal model where the anticancer effect of the developed Fu-MSN@MTX-NMOF was compared to the sequentially administrated free drugs. The results revealed enhanced anti-tumor effect while maintaining the normal functions of the vital organs as the heart, kidney and liver.

Folic/lactobionic acid dual-targeted polymeric nanocapsules for potential treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor that affects many patients diagnosed with hepatic cell inflammation and liver cirrhosis. Targeted polymeric nanocapsules could facilitate the internalization and accumulation of anticancer drugs. Dual-targeted folic acid/lactobionic acid-poly lactic co-glycolic acid nanocapsules (NCs) were prepared and loaded with pterostilbene (PTN) and characterized for their physicochemical properties, as well as in vitro and in vivo anticancer activity. NCs displayed a size of 222 nm, zeta potential of - 16.5 mV, and sustained release for 48 h. The IC50 of PTN NCs (5.87 ± 0.8 µg/mL) was 20 times lower than unencapsulated PTN (121.26 ± 9.42 µg/mL) on HepG2 liver cancer cells owing to the enhanced cellular uptake of the former, as delineated by flow cytometry. In vivo study on HCC-induced animals delineated the superiority of the dual-targeted NCs over the unencapsulated PTN, which significantly reduced the liver markers ALT, AST, and ALP, as well as the tumor-related markers AFP and Bcl2, and elevated the anti-apoptotic marker caspase 3. Furthermore, the NCs significantly reduced the oxidative stress and exhibited almost comparable histological features to the normal group. Therefore, it can be concluded that the dual-ligated folic acid/lactobionic acid nanocapsules can be considered a promising potential treatment option for hepatocellular carcinoma.

Imprinted Polymers on the Route to Plastibodies for Biomacromolecules (MIPs), Viruses (VIPs), and Cells (CIPs).

Around 30% of the scientific papers published on imprinted polymers describe the recognition of proteins, nucleic acids, viruses, and cells. The straightforward synthesis from only one up to six functional monomers and the simple integration into a sensor are significant advantages as compared with enzymes or antibodies. Furthermore, they can be synthesized against toxic substances and structures of low immunogenicity and allow multi-analyte measurements via multi-template synthesis. The affinity is sufficiently high for protein biomarkers, DNA, viruses, and cells. However, the cross-reactivity of highly abundant proteins is still a challenge.

Fluorescent molecularly imprinted polymer nanocomposite for solid-phase extraction and fluorimetric determination of hydrochlorothiazide.

We report herein a fluorescent molecularly imprinted polymer (FMIP) for the solid-phase extraction (SPE) and fluorimetric determination of hydrochlorothiazide (HCTZ) in water. The FMIP is based on fluorescent polystyrene nanoparticles embedded within a molecularly imprinted polyaniline (PANI) matrix. The operational adsorption parameters such as the initial HCTZ concentration, incubation time and the solution pH were found to influence the removal efficiency. At optimum conditions, a high adsorption capacity of the FMIP was found (2.08 mg g-1). Evidence of the adsorption process was confirmed by the change in the FMIP physicochemical properties measured by FTIR absorption spectroscopy and electron microscopy. Based on the regression R2 values and the consistently low values of the adsorption statistical error functions, equilibrium data were best fitted to both Freundlich and Temkin isotherms. Moreover, the pseudo-second-order kinetic model described the adsorption kinetics, and the mechanism of the adsorption process was explained by the intraparticle diffusion model. Upon studying adsorption thermodynamics, negative ΔG values (-26.18 kJ mol-1 at room temperature) were obtained revealing that the adsorption process is spontaneous. Interestingly, the maximum adsorption capacity was obtained at 298 K, pH 7.0, and using a high HCTZ concentration, thus revealing the suitability of the proposed FMIP for easy and fast SPE of HCTZ. The FMIP showed an imprinting factor of 1.19 implying the selectivity over the corresponding FNIP. Eventually, the proposed FMIP was successfully applied to the spectrofluorimetric determination of HCTZ in aqueous samples with %recovery values close to 100%.

Surface grafting of polymeric catheters and stents to prevent biofilm formation of pathogenic bacteria.

BACKGROUND: Tecothane (medical grade of polyurethane) is strongly involved in the fabrication of metallic and polymeric-based medical devices (e.g., catheters and stents) as they can withstand cardiac cycle-related forces without deforming or failing, and they can mimic tissue behavior. The main problem is microbial contamination and formation of pathogenic biofilms on such solid surfaces within the human body. Accordingly, our hypothesis is the coating of tecothane outer surfaces with antibacterial agents through the electro-deposition or chemical grafting of anti-biofilm agents onto the stent and catheter surfaces. RESULTS: Tecothane is grafted with itaconic acid for cross-linking the polyethyleneimine (PEI) as the protective-active layer. Accordingly, the grafting of poly-itaconic acid onto the Tecothane was achieved by three different methods: wet-chemical approach, electro-polymerization, or by using plasma treatment. The successful modifications were verified using Fourier Transform Infrared (FTIR) spectroscopy, grafting percentage calculations, electrochemical, and microscopic monitoring of biofilm formation. The grafting efficiency of itaconic acid was over 3.2% (w/w) at 60 â„ƒ after 6 h of the catheter chemical modification. Bio-electrochemical signals of biofilms have been seriously reduced after chemical modification because of the inhibition of biofilm formation (for both Pseudomonas aeruginosa and Staphylococcus aureus) over a period of 9 days. CONCLUSION: Chemical functionalization of the polyurethane materials with the antimicrobial and anti-biofilm agents led to a significant decrease in the formation of pathogenic biofilms. This promising proof-concept will open the door to explore further surface protection with potential anti-biofilm agents providing better and sustainable productions of stents and catheters biomaterials.

3D-bioimplants mimicking the structure and function of spine units for the treatment of spinal tuberculosis.

Approximately 1-2% of the reported tuberculosis (TB) cases have skeletal system problems, particularly spinal TB. The complications of spinal TB involve the destruction of vertebral body (VB) and intervertebral disc (IVD) which consequently leads to kyphosis. This work aimed at utilizing different technologies to develop, for the first time, a functional spine unit (FSU) replacement to mimic the structure and function of the VB and IVD along with a good ability to treat spinal TB. 3D-printed scaffolds with different porous patterns (hexagonal or grid) were fabricated from biocompatible acrylonitrile butadiene styrene, and polylactic acid to replace damaged VB and IVD, respectively. The VB scaffold is filled with gelatine-based semi-IPN hydrogel containing mesoporous silica nanoparticles loaded with two antibiotics, rifampicin and levofloxacin, to act against TB. The IVD scaffold incorporates a gelatin hydrogel loaded with regenerative platelet-rich plasma and anti-inflammatory simvastatin-loaded mixed nanomicelles. The obtained results confirmed the superior mechanical strength of both 3D-printed scaffolds and loaded hydrogels as compared to normal bone and IVD with high in vitro (cell proliferation, anti-inflammation and anti-TB), and in vivo biocompatibility profiles. Moreover, the custom-designed replacements have achieved the expected prolonged release of antibiotics up to 60 days. Given the promising study findings, the utilization of the developed drug-eluting scaffold system can be extrapolated to treat not only spinal TB but also to resolve diverse backbone/spine problems that need a critical surgical process including degenerative IVD and its consequences like atherosclerosis, sliding or spondylolisthesis and severe traumatic bone fracture.

Core-Shell Nanostructured Drug Delivery Platform Based on Biocompatible Metal-Organic Framework-Ligated Polyethyleneimine for Targeted Hepatocellular Carcinoma Therapy.

Multifunctional nanosized metal-organic frameworks (NMOFs) have advanced rapidly over the past decade to develop drug delivery systems (DDSs). These material systems still lack precise and selective cellular targeting, as well as the fast release of the quantity of drugs that are simply adsorbed within and on the external surface of nanocarriers, which hinders their application in the drug delivery. Herein, we designed a biocompatible Zr-based NMOF with an engineered core and the hepatic tumor-targeting ligand, glycyrrhetinic acid grafted to polyethyleneimine (PEI) as the shell. The improved core-shell serves as a superior nanoplatform for efficient controlled and active delivery of the anticancer drug doxorubicin (DOX) against hepatic cancer cells (HepG2 cells). In addition to their high loading capacity of 23%, the developed nanostructure DOX@NMOF-PEI-GA showed an acidic pH-stimulated response and extended the drug release time to 9 days as well as enhanced the selectivity toward the tumor cells. Interestingly, the DOX-free nanostructures showed a minimal toxic effect on both normal human skin fibroblast (HSF) and hepatic cancer cell line (HepG2), but the DOX-loaded nanostructures exhibited a superior killing effect toward the hepatic tumor, thus opening the way for the active drug delivery and achieving efficient cancer therapy applications.

Investigation of thymine as a potential cancer biomarker employing tryptophan with nanomaterials as a biosensor.

Tryptophan and tryptophan-based nanomaterials sensors in a solution have been developed to directly evaluate thymine. The determination of thymine has been done via quenching of the fluorescence of tryptophan and tryptophan-based nanomaterials such as graphene (Gr), graphene oxide (GO), gold nanoparticles (AuNPs), gold-silver nanocomposite (Au-Ag NC) in a physiological buffer. As the concentration of thymine rises, the fluorescence of tryptophan and tryptophan/nanomaterials becomes less intense. Trp, Trp/Gr, and tryptophan/(Au-Ag) NC systems' quenching mechanisms were dynamic, but tryptophan /GO and tryptophan/AuNPs' quenching mechanisms were static. The linear dynamic range for the determination of thy by tryptophan and tryptophan /nanomaterials is 10 to 200 µM. The detection limits for tryptophan, tryptophan /Gr, tryptophan /GO, tryptophan /AuNPs, and tryptophan/Au-Ag NC were 3.21, 14.20, 6.35, 4.67and 7.79 Μm, respectively. Thermodynamic parameters for the interaction of the Probes with Thy include the enthalpy (H°) and entropy (S°) change values, were assessed, as well as the binding constant (Ka) of Thy with Trp and Trp-based nanomaterials. A recovery study was conducted utilizing a human serum sample after the addition of the required quantity of the investigational thymine.

An in-vitro quantitative investigation on the synergistic effect of capsaicin and 5-fluorouracil encapsulated into lipid nanocapsules to treat breast cancer.

BACKGROUND: Breast cancer conventional therapeutics are effective; however, they encounter some limitations including multidrug resistance, the presence of pharmacological barriers, and non-selectivity which hinder their optimal therapeutic efficacy. AIM: Overcoming such drawbacks necessitates the development of efficient drug vehicles including lipid-based nanoparticles. This study aimed to quantitatively investigate in-vitro the synergistic therapeutic effect of the novel combination of capsaicin and 5-fluorouracil (5-FU) encapsulated in lipid nanocapsules (LNCs). METHOD: To this end, thorough physicochemical and in-vitro assessments on the breast cancer cell line (MCF-7) were done. The drug-loaded LNCs were characterized using DLS, TEM imaging, stability study, and in-vitro release study. Furthermore, the biological activity of the prepared LNCs was assessed by implementing comparative cytotoxicity studies as well as apoptosis, and cell cycle flow cytometric analyses. RESULTS: The developed nanoformulations were monodisperse with average particle size (PS) of 31, 43.8, and 127.3 nm for empty LNCs, Cap-LNCs, and 5-FU-LNCs, respectively, and with a surface charge of -35.4, -21.7 and -31.4 mV, respectively, reflecting good physical stability. The TEM micrographs revealed the spherical morphology of the drugs-loaded LNCs with comparable PS to that obtained by DLS. on the other hand, all the biological assessments confirmed the superior antiproliferative effect of the combined drug-loaded LNCs over their free drug counterparts. CONCLUSION: Intriguingly, the study findings highlighted the potential synergistic activity of the drugs (capsaicin and 5-FU) and the extensive enhancement of their biological activity through incorporation into LNCs. Such promising results will pave the way to further novel combined nanoformulation in preclinical and clinical studies on breast cancer patients.

Correction: Mansour et al. Dual-Enhanced Pluronic Nanoformulated Methotrexate-Based Treatment Approach for Breast Cancer: Development and Evaluation of In Vitro and In Vivo Efficiency. Pharmaceutics 2022, 14, 2668.

In the original publication [...].

Design, development, in-vitro and in-vivo evaluation of polylactic acid-based multifunctional nanofibrous patches for efficient healing of diabetic wounds.

Impaired healing of diabetic ulcers is one of the major complications of diabetic patients due to high susceptibility to microbial infections, impaired lymphianogenesis, edema, and consequently impairing proper healing. This could even lead to much worse complications that include severe gangrene, trauma and finally limb amputation. Therefore, this study aims to develop a multilayered durable nanofibrous wound patch loaded with three promising drugs (phenytoin, sildenafil citrate and simvastatin) each in a separate layer to target a different wound healing phase. Polylactic acid was used for the preparation of the nanofibrous matrix of the wound patch, where each drug was incorporated in a separate layer during the preparation process. Drugs release profiles were studied over 3 weeks. Results showed that both phenytoin and simvastatin were released within 14 days while sildenafil continued till 21 days. Both physicochemical and mechanical characteristics of the patches were fully assessed as well as their biodegradability, swellability, breathability and porosity. Results showed that incorporation of drugs preserved the physicochemical and mechanical properties as well as porosity of the developed nanofibers. In addition, patches were evaluated for their biocompatibility and cell adhesion capability before being tested through in-vivo diabetic wound rat model induced by alloxan for three weeks. In vivo results showed that the patches were successful in inducing proper wound healing in diabetic rat model with overcoming the above-mentioned obstacles within 3 weeks. This was confirmed through assessing wound closure as well as from histopathological studies that showed complete healing with proper cell regeneration and arrangement without forming scars.

Fortified anti-proliferative activity of niclosamide for breast cancer treatment: In-vitro and in-vivo assessment.

Breast cancer represents one of the top lethal cancer types among the females worldwide. Several factors manipulate the clinical outcome of the treatment as the stage of the cancer upon detection, genetic and hormonal factors, drug resistance and metastasis. Accordingly, drug's repositioning, enhancing the bioavailability and encapsulation into nanoparticles (NPs) are among the predilected pathways for enhanced therapeutic outcome. Niclosamide (NIC) is an anthelmintic drug and has been repositioned as anticancer agent after revealing its anti-neoplastic activity. Piperine (PIP) was used as food spice until its anticancer activity was discovered. However, their hydrophobicity constrains their therapeutic efficiency. The cytotoxicity of both drugs in the free form was tested on MCF-7 cells, and the results indicated a NIC cytotoxicity enhancement by PIP. Then, NIC and PIP were encapsulated successfully into F127-NPs with entrapment efficiency of 97 % and 82 %, respectively. Particle size, zeta potential, TEM and FTIR confirmed the micellization process and drug encapsulation. The developed NIC-NPs and PIP-NPs exerted potent anticancer effect as compared to the free forms. Accordingly, the mixture; NIC-NPs/PIP-NPs was tested and its cytotoxicity exceeded the individually encapsulated drugs. Flowcytometry assessment was performed and demonstrated an induced cell death through the apoptotic stage. Additionally, in-vivo therapeutic efficiency of NIC-NPs/PIP-NPs was assessed through Ehrlich ascites tumor and the nanocombination therapy exerted superior additive anticancer effect when compared to NIC-NPs which is attributed to the PIP-NPs induced bioavailability. The study can be considered the first one investigating the PIP role in bioenhancing the anti-proliferative activity of NIC to combat breast cancer.

Dual antituberculosis drugs-loaded gelatin hydrogel bioimplant for treating spinal tuberculosis.

Spinal tuberculosis (TB) represents around 1% of the recorded TB with a high mortality rate due to neurological complications and kyphosis. The current work aimed to develop a bioimplant scaffold to treat spinal TB disease. The scaffold is composed of a biocompatible semi-interpenetrating (semi-IPN) gelatin-based hydrogel incorporating mesoporous silica nanoparticles (MPS-NPs) loaded with rifampicin (RIF) and levofloxacin (LEV) to treat TB. The elastic modulus of the hydrogel was 7.18 ± 0.78 MPa. Minimum inhibitory concentrations (MIC) value against Mycobacterium bovis for LEV-loaded and RIF-loaded MPS-NPs were 6.50 and 1.33 µm/ml, respectively.Sequential release of drugs was observed after 15 days. Loading of the MPS-NPs in the hydrogel matrix governed the amount of released drugs by prolonging the period of release up to 60 days. WST-1 test confirmed the biocompatibility and safety of the developed vertebral hydrogel bioimplant. Histological and immunohistochemistry micrographs showed the progress in healing process with the bioimplant. Besides, loading of LEV and RIF in the implants declined the presence of the giant macrophages clusters as compared to control groups. All the obtained results support the potential use of the developed vertebral hydrogel bioimplant as a scaffold with good mechanical and biocompatible properties along with a good ability to eradicate the TB pathogen.

Post grafted gallic acid to chitosan-Ag hybrid nanoparticles via free radical-induced grafting reactions.

The present study proposes two unique systems using free radical-induced grafting reactions to combine Ag, chitosan (CS) and gallic acid (GA) into a single particulate nanostructure. GA-grafted-CS (GA-g-CS) was used to reduce Ag+ to Ag0, and producing Ag-GA-g-CSNPs (hybrid NPs I). Also, GA was grafted into CS-AgNPs, to form GA-g-CS AgNPs (hybrid NPs II). Although there were previous attempts to graft GA into CS, this is first time to graft GA into CS-AgNPs. The study aimed to enhance biocompatibility, antibacterial and antioxidant properties of CS-AgNPs via grafted GA. Grafting GA into CS-AgNPs was confirmed by UV-Vis, DLS, DSC/TGA, XRD, EDX and FTIR. The morphology and size of NPs were studied by TEM and SEM. The decrease of ζ-potential from +50 mV in CS-Ag NPs to +33 and + 29 mV, in the presented 2 nanoforms hybrid NPs I and II, respectively, is an indication for the successful GA graft. Among all samples, hybrid NPs II showed lower toxicity, higher antioxidant and antibacterial activity. The obtained results revealed that grafting GA to CS-AgNPs, as a new method to combine Ag, CS and GA in a uniparticulate structure, is a unique process which may deserve a more future consideration.