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.

Placental Nanoparticle Uptake-On-a-Chip: The Impact of Trophoblast Syncytialization and Shear Stress.

The placenta is a dynamic and complex organ that plays an essential role in the health and development of the fetus. Placental disorders can affect the health of both the mother and the fetus. There is currently an unmet clinical need to develop nanoparticle-based therapies to target and treat placental disorders. However, little is known about the interaction of nanoparticles (NPs) with the human placenta under biomimetic conditions. Specifically, the impact of shear stress exerted on the trophoblasts (placental epithelial cells) by the maternal blood flow, the gradual fusion of the trophoblasts along the gestation period (syncytialization), and the impact of microvilli formation on the cell uptake of NPs is not known. To this end, we designed dynamic placenta-on-a-chip models using BeWo cells to recapitulate the micro-physiological environment, and we induced different degrees of syncytialization via chemical induction with forskolin. We characterized the degree of syncytialization quantitatively by measuring beta human chorionic gonadotropin (ß-hCG) secretion, as well as qualitatively by immunostaining the tight junction protein, ZO-1, and counter nuclear staining. We also characterized microvilli formation under static and dynamic conditions via F-actin staining. We used these models to measure the cell uptake of chondroitin sulfate a binding protein (CSA) conjugated and control liposomes using confocal microscopy, followed by image analysis. Interestingly, exposure of the cells to a dynamic flow of media intrinsically induced syncytialization and microvilli formation compared to static controls. Under dynamic conditions, BeWo cells produced more ß-hCG in conditions that increased the cell exposure time to forskolin (p < 0.005). Our cell uptake results clearly show a combined effect of the exerted shear stress and forskolin treatment on the cell uptake of liposomes as uptake increased in forskolin exposed conditions (p < 0.05). Overall, the difference in the extent of cell uptake of liposomes among the different conditions clearly displays a need for the development of dynamic models of the placenta that consider the changes in the placental cell phenotype along the gestation period, including syncytialization, microvilli formation, and the expression of different transport and uptake receptors. Knowledge generated from this work will inform future research aiming at developing drug delivery systems targeting the placenta.

Efficacy of biocompatible trilayers nanofibrous scaffold with/without allogeneic adipose-derived stem cells on class II furcation defects of dogs' model.

OBJECTIVE: This study aimed to evaluate the regenerative capacity of a newly-developed polycaprolactone (PCL)-based nanofibrous composite scaffold either alone or in combination with adipose-derived mesenchymal stem cells (ADSCs) as a treatment modality for class II furcation defects. MATERIALS AND METHODS: After ADSCs isolation and scaffold characterization, the mandibular premolars of adult male mongrel dogs were selected and randomly assigned into three equal groups. In group I, class II furcation defects were surgically induced to the inter-radicular bone. While class II furcation defects of group II were induced as in group I. In addition, the defects were filled with the prefabricated scaffold. Moreover, class II furcation defects of group III were induced as in group II and instead the defects were filled with the prefabricated scaffold seeded with ADSCs. The dogs were sacrificed at 30 days or at 60 days. Periodontal wound healing/regeneration was evaluated by radiological examination using cone beam computed tomography and histologically using ordinary, histochemical, and immunohistochemical staining. RESULTS: In the two examination periods, group II defects compared to group I, and group III compared to the other groups showed a decrease in defect dimensions radiographically. Histologically, histochemically, and immunohistochemically, they significantly demonstrated better periodontal wound healing/regeneration, predominant collagen type I of newly formed bone and periodontal ligament with a significant increase in the immunoreactivity of vascular endothelial growth factor and osteopontin. CONCLUSIONS: The newly fabricated nanofibrous scaffold has enhanced periodontal wound healing/regeneration of class II furcation defects with further enhancement achieved when ADSCs seeded onto the scaffold before implantation. CLINICAL RELEVANCE: The implementation of our newly-developed PCL-based nanofibrous composite scaffolds in class II furcation defect either alone or in conjunction with ADSCs can be considered as a suitable treatment modality to allow periodontal tissues regeneration.

Novel Nano-Therapeutic Approach Actively Targets Human Ovarian Cancer Stem Cells after Xenograft into Nude Mice.

The power of tumorigenesis, chemo-resistance and metastasis in malignant ovarian tumors resides in a tiny population of cancer cells known as ovarian cancer stem cells (OCSCs). Developing nano-therapeutic targeting of OCSCs is considered a great challenge. The potential use of poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) was investigated as a drug delivery system for paclitaxel (PTX) against OCSCs in vitro and in vivo. PTX-loaded PLGA NPs were prepared by an emulsion solvent evaporation method, supported by incorporation of folic acid (FA) as the ligand. NPs were characterized for size, surface morphology, drug loading, and encapsulation efficiency. In vitro cytotoxicity of PTX-loaded FA/PLGA NPs was tested against OCSCs with MTT assay. In vivo anti-tumoral efficiency and active targeting potential of prepared NPs against tumors in nude mice were investigated. In vitro results revealed that IC50 of PTX was significantly reduced after loading on PLGA NPs. On the other hand, in vivo results showed that PLGA NPs enhanced the tumor suppression efficiency of PTX. Investigation with real time quantitative PCR analysis revealed the limiting expression of chemo-resistant genes (ABCG2 and MDR1) after applying PLGA NPs as a drug delivery system for PTX. Histopathological examination of tumors showed the effective biological influence of PTX-loaded FA/PLGA NPs through the appearance of reactive lymphoid follicles. Targeting potential of PTX was activated by FA/PLGA NPs through significant preservation of body weight (p < 0.0001) and minimizing the systemic toxicity in healthy tissues. Immunohistochemical investigation revealed a high expression of apoptotic markers in tumor tissue, supporting the targeting effect of FA/PLGA NPs. A drug delivery system based on FA/PLGA NPs can enhance PTX's in vitro cytotoxicity and in vivo targeting potential against OCSCs.

A new modification for improving shear bond strength and other mechanical properties of conventional glass-ionomer restorative materials.

PURPOSE: To study the effect of addition of poly(acrylamide-co-sodium acrylate) copolymer and/or TiO2 nanoparticles on the mechanochemical properties of conventional glass ionomer (GIC)-based restorative materials. MATERIALS AND METHODS: The copolymer was prepared, characterized and then added, either separately or in combination with different proportions of TiO2 nanoparticles to the conventional GIC powder. The developed composites were characterized using FTIR spectrometry, x-ray diffraction, and scanning electron microscopy. The mechanical properties of the obtained series of modified GIC formulations were investigated in comparison with other formulations containing only TiO2 nanoparticles through testing their compressive strength, flexural strength, and dentin shear bond strength. RESULTS: The preliminary data of the study showed a significant increase in the compressive strength of the conventional GIC after addition of 3% and 5% TiO2 nanoparticles by weight, but 7% decreased it. Upon addition of copolymer, the compressive strength was lower than that of the conventional GIC. The highest average compressive strength value was obtained upon incorporation of 7% 1:1 combination of copolymer-TiO2 nanoparticles. The results also demonstrated a significant increase in the flexural strength values after addition of both copolymer and TiO2 nanoparticles to the GIC powder. In addition, the results revealed a significant increase in values of dentin shear bond strength after copolymer addition with the highest value noted upon addition of 7% by weight of copolymer. CONCLUSION: The new series of modified glass ionomers developed here can be tailored to act as restorative materials with high quality performance in high stress-bearing areas.

Swellable ciprofloxacin-loaded nano-in-micro hydrogel particles for local lung drug delivery.

Incorporation of drug-loaded nanoparticles into swellable and respirable microparticles is a promising strategy to avoid rapid clearance from the lung and achieve sustained drug release. In this investigation, a copolymer of polyethylene glycol grafted onto phthaloyl chitosan (PEG-g-PHCs) was synthesized and then self-assembled with ciprofloxacin to form drug-loaded nanoparticles. The nanoparticles and free drug were encapsulated into respirable and swellable alginate micro hydrogel particles and assessed as a novel system for sustained pulmonary drug delivery. Particle size, morphology, dynamic swelling profile, and in vitro drug release were investigated. Results showed that drug-loaded nanoparticles with size of 218 nm were entrapped into 3.9-µm micro hydrogel particles. The dry nano-in-micro hydrogel particles exhibited a rapid initial swelling within 2 min and showed sustained drug release. Preliminary in vivo pharmacokinetic studies were performed with formulations delivered to rats by intratracheal insufflation. Ciprofloxacin concentrations in plasma and in lung tissue and lavage were measured up to 7 h. The swellable particles showed lower ciprofloxacin levels in plasma than the controlled group (a mixture of lactose with micronized ciprofloxacin), while swellable particles achieved higher concentrations in lung tissue and lavage, indicating the swellable particles could be used for controlling drug release and prolonging lung drug concentrations.

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.

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.

Controlled release pulmonary administration of curcumin using swellable biocompatible microparticles.

This study involves a promising approach to achieve sustained pulmonary drug delivery. Dry powder particulate carriers were engineered to allow simultaneous aerosol lung delivery, evasion of macrophage uptake, and sustained drug release through a controlled polymeric architecture. Chitosan grafted with PEG was synthesized and characterized (FTIR, EA, DSC and 2D-XRD). Then, a series of respirable amphiphilic hydrogel microparticles were developed via spray drying of curcumin-loaded PLGA nanoparticles with chitosan-grafted-PEG or chitosan. The nanoparticles and microparticles were fully characterized using an array of physicochemical analytical methods including particle size, surface morphology, dynamic swelling, density, moisture content and biodegradation rates. The PLGA nanoparticles and the hydrogel microspheres encapsulating the curcumin-loaded PLGA nanoparticles showed average size of 221-243 nm and 3.1-3.9 µm, respectively. The developed carriers attained high swelling within a few minutes and showed low moisture content as dry powders (0.9-1.8%), desirable biodegradation rates, high drug loading (up to 97%), and good sustained release. An aerosolization study was conducted using a next generation impactor, and promising aerosolization characteristics were shown. In vitro macrophage uptake studies, cytotoxicity and in vitro TNF-α assays were performed for the investigated particles. These assays revealed promising biointeractions for the respirable/swellable nano-micro particles developed in this study as potential carriers for sustained pulmonary drug delivery.

New repurposed rolapitant in nanovesicular systems for lung cancer treatment: Development, in-vitro assessment and in-vivo biodistribution study.

Lung cancer is characterized by poor prognosis, and is considered a serious disease that causes a significant mortality. The available conventional chemotherapeutic agents suffer from several limitations; hence, new drug molecules are constantly being sought. In the current study, lipid nanovesicles (LNVs) were selected as a colloidal vehicle for encapsulation of the FDA-approved drug; rolapitant (RP), which is used particularly for the treatment of nausea and vomiting, but is repurposed for the treatment of lung cancer in the current work. RP was loaded into various LNVs (liposomes, ethosomes and transethosomes) using the thin film hydration method, and the LNVs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), storage stability and surface morphology. Besides, the in-vitro drug release, in-vitro cytotoxicity on A549 lung cancer cells, nebulization performance using next generation impactor (NGI), and the in-vivo biodistribution behavior were evaluated. The selected ethosomal and transethosomal vesicles displayed a particle size less than 400 nm, a positive charge, and EE% exceeding 90% for RP, with a sustained release pattern over 15 days. The in-vivo biodistribution results proved the high lung deposition potential of RP-LNVs with a considerable safety. Besides, the developed RP-LNVs were able to reach the metastatic organs of lung cancer, hence they were proven promising as a possible treatment modality for lung cancer.

Nanomicelles-in-coaxial nanofibers with exit channels as a transdermal delivery platform for smoking cessation.

Smoking is a life-threatening habit; that is why many nicotine-replacement therapies (NRTs), which include chewing gums, nicotine patches, lozenges, mouth sprays, inhalers and nasal sprays that are usually administered for 8-12 weeks, have been reported for smoking cessation. We report the fabrication of patches comprising nanomicelles-in-coaxial nanofibers (NFs) for the transdermal delivery of varenicline (VAR) tartrate, a partial agonist of the α4ß2 receptor subtype, for smoking cessation. The cores of the fabricated coaxial NF structures are composed of polyethylene oxide, VAR-loaded Pluronic F127 nanomicelles (NPs) and free VAR, while the shell consists of a blend of cellulose acetate (CA) and polycaprolactone (PCL) in a ratio of 1 : 9 (w/w) that incorporates 50% (wt%) free VAR. The morphology and the coaxial structure of the NFs were investigated using TEM, SEM and fluorescent microscopy. The physicochemical and mechanical properties of the scaffolds were analyzed using FTIR, DSC, DLS, TGA and a universal testing machine. SEM micrographs depict NFs with a size ranging from 793.7 ± 518.9 to 324.5 ± 144.1 nm. In vitro release of VAR reaches almost 100% after 3, 9 and 28 days for free VAR, VAR-loaded NPs and the NPs-in-NFs patches, respectively, while the ex vivo release tested using albino rat skin, over a period of 60 days, showed up to 94% sustained release of VAR. Besides, skin permeation, in vivo release and plasma concentrations of VAR from the NF transdermal patches were monitored via cyclic voltammetric measurements during the course of treatment. DFT calculations as well as mathematical release kinetic models were performed in order to study the release mechanism. The cell viability of human skin fibroblast (HSF) cells in the case of plain and VAR-loaded NFs was 75.09 and 32.11%, respectively. The in vivo results showed that VAR was being continuously released from the transdermal patch over a period of 14 days. Besides, the treatment with VAR-loaded patches did not cause any severe conditions in the studied animal model. The new fabricated NPs-in-NFs transdermal patch for VAR tartrate delivery is considered as an effective, economic, safe and long-acting NRT for smoking cessation.

Switching indication of PEGylated lipid nanocapsules-loaded with rolapitant and deferasirox against breast cancer: Enhanced in-vitro and in-vivo cytotoxicity.

Breast cancer (BC) is considered the leading cause of mortality and morbidity among adult women worldwide, and it is associated with many genetic or hormonal factors. Despite the advanced therapeutic and theranostic strategies for BC treatment, cancer metastasis and relapse are often observed among patients which lead to therapeutic failure. Accordingly, among the repositioned medication against BC proliferation is neurokinin receptor antagonists and iron chelating agents especially rolapitant HCl (RP) and deferasirox (DFO), respectively. However, RP and DFO are classified as class II with low aqueous solubility. Both drugs were nanoformulated into PEGylated lipid nanocapsules (LNCs) for enhancing their aqueous solubility and augmenting their efficacy. RP-LNCs, DFO-LNCs and their combinations were evaluated according to particle size (PS), zeta potential, polydispersity index (PDI) and surface morphology. Importantly, the antitumor effect of these novel molecules and their nanoforms was evaluated against the suppression of Ehrlich Ascites tumor model using female mice. Results revealed that RP-LNCs, DFO-LNCs and RP/DFO-LNCs exerted PS from 45.23 ± 3.54 to 60.1 ± 3.32 nm with PDI around 0.20 which indicates homogenous particles distribution. Also, RP-LNCs, DFO-LNCs and RP/DFO-LNCs displayed surface charges of +16.6 ± 6.9, -13.3 ± 5.82 and - 20.2 ± 5.40 mV, respectively. The obtained LNCs conferred a high potent cytotoxic effect against MCF7 cancer cells as compared to parent drugs, with IC50 of 10.86 ± 0.89, 3.34 ± 0.99 and 2.24 ± 0.97 µg/mL for RP-LNCs, DFO-LNCs and RP/DFO-LNCs, respectively. The in-vivo pharmacodynamics effect of the developed nano-formulations showed superior antitumor effect for the individual drugs rather than their combinations as compared to the control group. The current study confirmed the potential of RP and DFO nanoforms as promising therapeutic agents for BC treatment.

Novel doxorubicin / folate-targeted trans-ferulic acid-loaded PLGA nanoparticles combination: In-vivo superiority over standard chemotherapeutic regimen for breast cancer treatment.

AIM: Doxorubicin/Cyclophosphamide (AC) is one of the standard adjuvant anthracycline-containing regimens that is still in use for breast cancer treatment. Cancer cell resistance and AC-induced side effects make treatment suboptimal and worsen patients' quality of life. This study aimed to improve trans-ferulic acid's (TFA) efficiency via loading into folate-receptor-targeted-poly lactic-co-glycolic acid nanoparticles (FA-PLGA-TFA NPs). Also, investigating both the antitumor efficacy of Doxorubicin (Dox)/FA-PLGA-TFA NPs combination against dimethylbenz[a]anthracene (DMBA)-induced breast cancer and its safety profile. METHODS: FA-PLGA-TFA NPs were optimally fabricated and characterized. Levels of Notch1, Hes1, Wnt-3a, ß-catenin, MMP-9, cyclin D1, Permeability-Glycoprotein (P-gp), ERα, PR, and HER2 were assessed as a measure of the antitumor efficacy of different treatment protocols. Histopathological examination of heart and bone, levels of ALT, AST, ALP, CK-MB, and WBCs count were evaluated to ensure the combination's safety profile. KEY FINDINGS: Dox/FA-PLGA-TFA NPs not only inhibited Notch signaling but also suppressed Notch synergy with Wnt, estrogen, progesterone, and HER2 pathways. Interestingly, Dox/FA-PLGA-TFA NPs decreased P-gp level and preserved heart, bone, and liver health as well as WBCs count. SIGNIFICANCE: Dox/FA-PLGA-TFA NPs reduced the side-effects of each single drug, and at the same time exerted excellent antitumor activity that surpass the AC regimen in evading cancer cell resistance and having a superior safety profile.

Antitumor activity and antioxidant role of a novel water-soluble carboxymethyl chitosan-based copolymer.

In this study, a natural polymer, chitosan (CS) has been converted through modified procedures to produce a water-soluble nontoxic form that has been evaluated as a novel potential antitumor drug. CS was carboxymethylated and then further modified in mild aqueous medium via graft copolymerization using a new simple and reproducible method. The synthesized new derivative of carboxymethylated CS (DCMC) was fully characterized by numerous techniques including Fourier transform infrared spectroscopy (FT-IR), elemental analyzer (EA), scanning electron microscopy (SEM), two-dimensional wide-angle X-ray scattering (2D-WAXS), and differential scanning calorimetry (DSC). The anticancer activity of the DCMC was investigated using mice bearing Ehrlich ascites tumor cells (EAC) at different doses dissolved in isotonic saline. It has been found that treatment with DCMC significantly inhibited tumor growth in a dose-dependent manner. To better understand the molecular mechanism explaining the DCMC effect on cancer cells, we tested the response of EAC cells in vivo to DCMC using flow cytometry cell cycle analysis. The cell cycle analysis revealed a G2/M phase accumulation as well as a significant increase in sub-G1 phase cells after treatment with DCMC. This indicates an induction of apoptosis in EAC cells associated with a highly significant decrease in tumor volume. In general, our results indicated that the DCMC is a regulator of tumor cell growth and differentiation not only by causing G2/M cell cycle arrest but also inducing their apoptotic death. Moreover, the estimated hematological profile such as hemoglobin, RBCs, as well as WBCs counts revealed normal levels in mice treated with DCMC, indicating the possibility of using the DCMC in cancer chemotherapy without causing anemia like other drugs. Biochemical assays also revealed that treatment with DCMC has led to an augmentation of the antioxidant defense system without affecting lipid peroxidation in EAC-bearing mice.

High selectivity detection of FMDV- SAT-2 using a newly-developed electrochemical nanosensors.

Foot-and-mouth disease virus serotype South-Africa territories-2 (FMDV-SAT-2) is the most fastidious known type in Aphthovirus which is subsequently reflected in the diagnosis regime. Rapid and early diagnostic actions are usually taken in response to the FMDV outbreak to prevent the dramatic spread of the disease. Virus imprinted sensor (VIP sensor) is gathering huge attention for the selective detection of pathogens. Thus, the whole virus particles of SAT-2 together with an electropolymerized film of poly(o-phenylenediamine) (PoPD) on gold-copper modified screen-printed electrode were applied to fabricate SAT-2-virus imprinted polymer (SAT-2-VIP). The SAT-2-VIPs were fully characterized using cyclic voltammetry (CV), linear sweep voltammetry (LSV), Atomic force microscopy (AFM), Scanning electron microscope (SEM), and Fourier transform Infra-Red (FTIR) spectroscopy. Excellent selective binding affinity towards the targeted virus particle was achieved with limits of detection and quantification of 0.1 ng/mL and 0.4 ng/mL, respectively. In terms of viral interference, the sensor did not show cross-reactivity towards other animal viruses including FMDV serotype A, O, or even SAT-2 subtype Libya and the un-related virus Lumpy skin disease virus (LSDV). This high selectivity provides a sensible platform with 70 folds more sensitivity than the reference RT-PCR as revealed from the application of SAT-2-VIP sensor for rapid analysis of clinical samples with no need for treatment or equipped labs. Thus, as diagnostic and surveillance technologies, on-site point of care diagnostics for SAT-2 virus are supported.

Boosting the antibacterial activity of chitosan-gold nanoparticles against antibiotic-resistant bacteria by Punicagranatum L. extract.

The present work describes the synthesis of a new series of chitosan-gold hybrid nanoparticles (CS-AuNPs) for the delivery of Punicagranatum L. extract (PE). It proposes CS and PE as reducing agents for gold ions in aqueous solution. The effect of PE on the physicochemical properties of the CS-AuNPs was investigated with UV spectroscopy, DLS, DSC, XRD, FTIR, SEM/EDX and TEM. Interestingly, about 50 % reduction in size was observed with using PE alone for gold reduction. The ζ-potential of CS-AuNPs was shifted from +53.1 ± 6.7 mV to 31.0 ± 6.0 mV upon conjugation of the negatively-charged PE polyphenols. The developed PE-conjugated CS-AuNPs exhibited higher stability at different pH values. About 87 % of the loaded PE was released from the NPs over 24 h. The antibacterial activity of CS-PE-AuNPs displayed a synergetic affect against methicillin-resistant S. aureus with MIC and MBC values of 15.6 and 62.5 µg/mL, respectively.

Dual-drug delivery of Ag-chitosan nanoparticles and phenytoin via core-shell PVA/PCL electrospun nanofibers.

Dual-drug delivery systems were constructed through coaxial techniques, which were convenient for the model drugs used the present work. This study aimed to fabricate core-shell electrospun nanofibrous membranes displaying simultaneous cell proliferation and antibacterial activity. For that purpose, phenytoin (Ph), a well-known proliferative agent, was loaded into a polycaprolactone (PCL) shell membrane, and as-prepared silver-chitosan nanoparticles (Ag-CS NPs), as biocidal agents, were embedded in a polyvinyl alcohol (PVA) core layer. The morphology, chemical composition, mechanical and thermal properties of the nanofibrous membranes were characterized by FESEM/STEM, FTIR and DSC. The coaxial PVA-Ag CS NPs/PCL-Ph nanofibers (NFs) showed more controlled Ph release than PVA/PCL-Ph NFs. There was notable improvement in the morphology, thermal, mechanical, antibacterial properties and cytobiocompatibility of the fibers upon incorporation of Ph and Ag-CS NPs. The proposed core-shell PVA/PCL NFs represent promising scaffolds for tissue regeneration and wound healing by the effective dual delivery of phenytoin and Ag-CS NPs.

Deacetylated cellulose acetate nanofibrous dressing loaded with chitosan/propolis nanoparticles for the effective treatment of burn wounds.

Every year, about 1 out of 9 get burnt in Egypt, with a mortality rate of 37%, and they suffer from physical disfigurement and trauma. For the treatment of second-degree burns, we aim at making a smart bandage provided with control of drug release (using chitosan nanoparticles) to enhance the healing process. This bandage is composed of natural materials; namely, cellulose acetate (CA), chitosan, and propolis (bee resin) as the loaded drug. Cellulose acetate nanofibers were deacetylated by NaOH after optimizing the reaction time and the concentration of NaOH solution, and the product was confirmed with FTIR analysis. Chitosan/propolis nanoparticles were prepared by ion gelation method with size ranging from 100 to 200 nm and a polydispersity index of 0.3. Chitosan/propolis nanoparticles were preloaded in the CA solution to ensure homogeneity. Loaded deacetylated cellulose nanofibers have shown the highest hydrophobicity measured by contact angle. Cytotoxicity of propolis and chitosan/propolis nanoparticles were tested and the experimental IC50 value was about 137.5 and 116.0 µg/mL, respectively, with p-value ≤0.001. In addition, chitosan/propolis nanoparticles loaded into cellulose nanofibers showed a cell viability of 89.46% in the cell viability test. In-vivo experiments showed that after 21 days of treatment with the loaded nanofibers repairing of epithelial cells, hair follicles and sebaceous glands in the skin of the burn wound were found in albino-mice model.

Fortified hyperbranched PEGylated chitosan-based nano-in-micro composites for treatment of multiple bacterial infections.

Bacterial resistance is a real threat to human health. One of the most common strategies used to overcome this problem is the combination therapy. This study proposes a new chitosan-based nano-in-microparticles (NIMs) antibacterial platform that can deliver multiple antibacterial therapeutics at the same time. Chitosan (CS) was PEGylated to overcome its limited water solubility. Then, the antibacterial activity of the resulting PEG-CS was fortified via conjugation with dendritic polyamidoamine hyperbranches (HB) as well as in-situ immobilization of silver nanoparticles (AgNPs) to be efficient against multiple bacterial strains. Montmorillonite nanoclay (MMT) was prepared and used to encapsulate ibuprofen (IBU) as anti-inflammatory drug to reduce any concomitant inflammatory response during bacterial infection. The successful synthesis of PEG-HBCS-AgNPs as well as IBU-MMT nanocomplex was confirmed using FTIR, 1H NMR, DSC, TGA and EDX. SEM micrographs showed a complete formation of NIM spherical particles with a size around 13 µm. Besides, the newly developed drugs-loaded CS-based NIM formulation showed a better widespread activity on the tested aerobic and anaerobic bacterial species, and it may represent, after further optimization, a promising approach for overcoming multiple-bacterial infection.

New alginate-based interpenetrating polymer networks for water treatment: A response surface methodology based optimization study.

Different interpenetrating polymeric networks (IPN) based on sodium alginate, carrageenan and bentonite were developed to remove heavy metals and dyes from contaminated water. Four significant preparation factors; crosslinking time, calcium chloride concentration, alginate to carrageenan mass ratio,and bentonite to carrageenan mass ratio were studied and optimized via full factorial design and response surface methodology to determine the optimum composition with highest adsorption capacity. Different optimal conditions and combinations were found depending on the type of heavy metal or dye to be removed. Low calcium chloride concentration was a common factor in all cases of heavy metals and dyes removal which indicates the negative effect of excessive crosslinking on the removal percentage. The adsorption capacity of methylene blue, Fe3+, Ni2+, and Cr3+ ions is 1271, 1550, 1500 and 1540 mg/g adsorbent, respectively. Reusability tests confirmed that the optimized formulations can be reused five successive times without significant drop in their removal efficiency. Upon utilization of the optimized formulations on real contaminated waters from tannery plant and oasis groundwater, they demonstrated an excellent performance as they removed above 95% of the original heavy metals contaminants and 40% of the acidic dye content.