Bioactive hybrid membrane-based cellulose acetate/bioactive glass/hydroxyapatite/carbon nanotubes nanocomposite for dental applications.

The present work aimed to fabricate a set of hybrid bioactive membrane in the form of bio-nanocomposite films for dental applications using the casting dissolution procedures. The formulation of the targeted materials was consisting of cellulose acetate/bioactive glass/hydroxyapatite/carbon nanotubes with a general abbreviation CA-HAP-BG-SWCNTs. The nanocomposites were characterized using XRD, FTIR, SEM-EDX and Raman spectroscopy. XRD, FTIR and SEM characters confirm the nanocomposites formation with good compatibility. The fabricated materials had a semi crystalline structure. The mechanical and thermal properties, as well as contact angle and bioactivity of the fabricated nanocomposites were investigated. The SEM images for showed beehive-like architectures with a thicker frame for the second material. All fabricated materials showed good thermal behaviors. Furthermore, the agar diffusion antimicrobial study showed that the prepared nanocomposites do not exhibit an antibacterial activity against five pathogenic bacterial strains. Additionally, cytotoxicity of a dental nanocomposite filling agent was evaluated. Vero normal cells were incubated with test materials for 72h at 37 °C and 5% CO2. Cell viability was detected using a SRB assay. All nanocomposites were mildly to non-cytotoxic to Vero cells at high concentration in contrast to the inhibitory effect of doxorubicin which was added at 10-fold lower concertation than the nanocomposites. Hence, the proposed nanocomposite is promising candidates for dental applications.

Impact of nanomaterials on sustainable pretreatment of lignocellulosic biomass for biofuels production: An advanced approach.

Biomass to biofuels production technology appears to be one of the most sustainable strategies among various renewable energy resources. Herein, pretreatment is an unavoidable and key step to increase free cellulose availability and digestibility to produce green fuels. Various existing pretreatment technologies of lignocellulosics biomasses (LCBs) face distinct challenges e.g., energy consuming, cost intensive, may lead partial removal of lignin, complex inhibitors production as well as may cause environmental pollutions. These, limitations may be overcome with the application of nanomaterials, employed as nanocatalysts during the pretreatment process of LCBs. In this prospect, the present review focuses and summarizes results of numerous studies and exploring the utilizations of magnetic, carbon based nanostructure, and nanophotocatalysts mediated pretreatment processes along with their possible mechanisms to improve the biofuels production compared to conventional chemical based pretreatment approaches. Furthermore, different aspects of nanomaterials based pretreatment methods with their shortcomings and future prospects have been discussed.

Utilization of a nanostructured lipid carrier encapsulating pitavastatin-Pinus densiflora oil for enhancing cytotoxicity against the gingival carcinoma HGF-1 cell line.

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer.

Enhancement in functional stability of microbial endoglanases produced using paddy straw via treatment with manganese oxide based porous nanocomposite synthesized from mixed fruit waste.

Microbial cellulases are the enzymes used in numerous industrial biotechnological applications. Efficiency of celluloytic cocktails plays a key role in the conversion of biomass into biofuels, but limited production, high cost and low efficiency are the main obstacles to sustainable biorefining. The current work aims to establish a feasible approach for boosting the production of fungal endoglucanse (EG) and its functional stability utilizing nanocomposite materials based on manganese oxide. Herein, aqueous extract from mixed fruit waste was used to synthesize the nanocomposite sample, which was subsequently subjected to several characterization techniques for analysis. Following the solid-state fermentation of paddy straw, and by employing 75 mg nanocomposite, 192 IU/gds EG was produced under the optimal conditions, while 19 IU/gds FP and 98 IU/gds BGL production were recorded. The crude EG enzyme treated with nanocomposite also shows complete stability at pH 5.0 for 3.5 h while retaining thermal activity at 70 °C for 4 h.

Green synthesis of nanostructures from rice straw food waste to improve the antimicrobial efficiency: New insight.

Applications for nanotechnology, which is constantly gaining prominence, have been found in a variety of industrial applications. Due to the multiple benefits associated with it, including an eco-friendly, pollution-free, cost-effective, and non-toxic synthesis method, the green way to synthesize nanostructures utilizing waste biomasses has become one of the key focuses of the current researches globally. Additionally, lignocellulasic biomass (LCB), which is a waste of the food crops, can be used as one of the potential substrates for the synthesis of a variety of nanostructures. Among different types of LCB, rice straw is a potential food waste biomass and can be efficiently employed during the synthesis of different types of nanostructures for a range of technological applications. Here, diverse phenolic compounds found in rice straw as well as reducing sugars can be used as natural reducing and capping agents to prepare a range of nanostructures. Based on the aforementioned facts, the objective of this review is to investigate the viability of using rice straw to produce nanostructured materials using rice straw as a renewable biosource following an environmentally friendly method. Additionally, it is noted that various organic compounds present on the surface of nanostructures produced using rice straw extract/hydrolyzate through a green approach may be more successful in terms of antibacterial efficacy, which might be of considerable interest for a variety of biomedical applications. Based on the possibility of enhancing the antimicrobial activity of developed nanostructures, the review also provides overview on the feasibility, characteristics, and availability of using rice straw extract in the synthesis of nanostructures. Additionally, the constraints of the present and potential futures of the green synthesis methods using rice straw wastes have been explored.

The Influence of Prenatal Exposure to Quetiapine Fumarate on the Development of Dopaminergic Neurons in the Ventral Midbrain of Mouse Embryos.

The effects of second-generation antipsychotics on prenatal neurodevelopment, apoptotic neurodegeneration, and postnatal developmental delays have been poorly investigated. Even at standard doses, the use of quetiapine fumarate (QEPF) in pregnant women might be detrimental to fetal development. We used primary mouse embryonic neurons to evaluate the disruption of morphogenesis and differentiation of ventral midbrain (VM) neurons after exposure to QEPF. The dopaminergic VM neurons were deliberately targeted due to their roles in cognition, motor activity, and behavior. The results revealed that exposure to QEPF during early brain development decreased the effects of the dopaminergic lineage-related genes Tyrosine hydroxylase(Th), Dopamine receptor D1 (Drd1), Dopamine transporter (Dat), LIM homeobox transcription factor 1 alfa (Lmx1a), and Cell adhesion molecule L1 (Chl1), and the senescent dopaminergic gene Pituitary homeobox 3 (Pitx3). In contrast, Brain derived neurotrophic factor (Bdnf) and Nuclear receptor-related 1 (Nurr1) expressions were significantly upregulated. Interestingly, QEPF had variable effects on the development of non-dopaminergic neurons in VM. An optimal dose of QEPF (10 µM) was found to insignificantly affect the viability of neurons isolated from the VM. It also instigated a non-significant reduction in adenosine triphosphate formation in these neuronal populations. Exposure to QEPF during the early stages of brain development could also hinder the formation of VM and their structural phenotypes. These findings could aid therapeutic decision-making when prescribing 2nd generation antipsychotics in pregnant populations.

Development of nanoemulsions for the delivery of hydrophobic and hydrophilic compounds against carbapenem-resistant Klebsiella pneumoniae.

Antimicrobial resistance (AR), particularly the limited antimicrobial activities of antibiotics and natural compounds, has prompted research into new antimicrobials. Nanoemulsions (NEs) have been found to improve the activity of antimicrobial compounds. This study developed clove essential oil-in-water NEs (CEO-NEs) and water-in-oil-in-water NEs co-encapsulating CEO and meropenem (CEO-MEM-NEs) to investigate the antibacterial activity of these loaded NEs against carbapenem-resistant Klebsiella pneumoniae. Ultrasonication was used to prepare CEO-NEs and CEO-MEM-NEs. Tween 80 and Imwitor 375 surfactants were used to produce CEO-NEs while Tween 80, Imwitor 375, and PGPR were used to produce CEO-MEM-NEs. Droplets' sizes were 138 ± 1.769 and 183.600 ± 0.889 for CEO-NEs and CEO-MEM-NEs, respectively. The resultant NEs were monodispersed, negatively charged, and physically stable. The antibacterial activities of NEs were investigated using broth microdilution, checkerboard, and time-kill assays to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). CEO-NEs (0.16% CEO MIC) and CEO-MEM-NEs (0.08% CEO and 1 µg mL-1 MEM MICs) completely inactivated K. pneumoniae, and showed functional stability after two weeks of storage at 4 °C. In conclusion, the formulated NEs significantly enhanced the antibacterial activity of CEO and MEM and have great potential as delivery systems of antimicrobial compounds.

Interrelation between extracellular vesicles miRNAs with chronic lung diseases.

Extracellular vehicles (EVs) are nanoscale lipid bilayer vesicles that carry biologically active biomolecule cargos like proteins, lipids, and nucleic acids (DNA, RNA) outside of the cell. Blood (serum/plasma), urine, and bronchoalveolar lavage fluid are all examples of biofluids from which they may be collected. EVs play a vital role in intracellular communication. The molecular signature of EVs largely depends on the parental cell's status. EVs are classified into two groups, (1) exosomes (originated by endogenous route) and (2) microvesicles (originated from the plasma membrane, also known as ectosomes). The quantity and types of EV cargo vary during normal conditions compared to pathological conditions (chronic inflammatory lung diseases or lung cancer). Consequently, EVs contain novel biomarkers that differ based on the cell type of origin and during lung diseases. Small RNAs (e.g., microRNAs) are transported by EVs, which is one of the most rapidly evolving research areas in the field of EVs biology. EV-mediated cargos transport small RNAs that can result in reprograming the target/recipient cells. Multiple chronic inflammatory lung illnesses, such as chronic obstructive pulmonary disease, asthma, pulmonary hypertension, pulmonary fibrosis, cystic fibrosis, acute lung injury, and lung cancer, have been demonstrated to be regulated by EV. In this review, we will consolidate the current knowledge and literature on the novel role of EVs and their small RNAs concerning chronic lung diseases (CLDs). Additionally, we will also provide better insight into the clinical and translational impact of mesenchymal stem cells-derived EVs as novel therapeutic agents in treating CLDs.

Synthesis, Characterization and In Vitro Evaluation of Chitosan Nanoparticles Physically Admixed with Lactose Microspheres for Pulmonary Delivery of Montelukast.

This study aimed to synthesise montelukast-loaded polymeric nanoparticles via the ionic gelation method using chitosan as a natural polymer and tripolyphosphate as a crosslinking agent. Tween 80, hyaluronic acid and leucine were added to modify the physicochemical properties of nanoparticles, reduce the nanoparticles' uptake by alveolar macrophages and improve powder aerosolisation, respectively. The nanoparticles ranged from 220 nm to 383 nm with a polydispersity index of ≤0.50. The zeta potential of nanoparticles ranged from 11 mV to 22 mV, with a drug association efficiency of 46-86%. The simple chitosan nanoparticles (F2) were more spherical in comparison to other formulations (F4-F6), while the roughness of hyaluronic acid (F5) and leucine (F6) added formulations was significantly high er than F2 and Tween 80 added formulation (F4). The DSC and FTIR analysis depict that the physical and chemical properties of the drug were preserved. The release of the drugs from nanoparticles was more sustained in the case of F5 and F6 when compared to F2 and F4 due to the additional coating of hyaluronic acid and leucine. The nanoparticles were amorphous and cohesive and prone to exhalation due to their small size. Therefore, nanoparticles were admixed with lactose microspheres to reduce particle agglomeration and improve powder dispersion from a dry powder inhaler (DPI). The DPI formulations achieved a dispersed fraction of 75 to 90%, a mass median aerodynamic diameter (MMAD) of 1-2 µm and a fine particle fraction (FPF) of 28-83% when evaluated using the Anderson cascade impactor from Handihaler®. Overall, the montelukast-loaded nanoparticles physically admixed with lactose microspheres achieved optimum deposition in the deep lung for potential application in asthmatic patients.

Prenatal Exposure to Gabapentin Alters the Development of Ventral Midbrain Dopaminergic Neurons.

Background: Gabapentin is widely prescribed as an off-label drug for the treatment of various diseases, including drug and alcohol addiction. Approximately 83-95% of the usage of gabapentin is off-label, accounting for more than 90% of its sales in the market, which indicates an alarming situation of drug abuse. Such misuse of gabapentin has serious negative consequences. The safety of the use of gabapentin in pregnant women has always been a serious issue, as gabapentin can cross placental barriers. The impact of gabapentin on brain development in the fetus is not sufficiently investigated, which poses difficulties in clinical decisions regarding prescriptions. Methods: The consequences effect of prenatal gabapentin exposure on the development of ventral midbrain dopaminergic neurons were investigated using three-dimensional neuronal cell cultures. Time-mated Swiss mice were used to isolate embryos. The ventral third of the midbrain was removed and used to enrich the dopaminergic population in 3D cell cultures that were subsequently exposed to gabapentin. The effects of gabapentin on the viability, ATP release, morphogenesis and genes expression of ventral midbrain dopaminergic neurons were investigated. Results: Gabapentin treatment at the therapeutic level interfered with the neurogenesis and morphogenesis of vmDA neurons in the fetal brain by causing changes in morphology and alterations in the expression of key developmental genes, such as Nurr1, Chl1, En1, Bdnf, Drd2, and Pitx3. The TH + total neurite length and dominant neurite length were significantly altered. We also found that gabapentin could halt the metabolic state of these neuronal cells by blocking the generation of ATP. Conclusion: Our findings clearly indicate that gabapentin hampers the morphogenesis and development of dopaminergic neurons. This implies that the use of gabapentin could lead to serious complications in child-bearing women. Therefore, caution must be exercised in clinical decisions regarding the prescription of gabapentin in pregnant women.

Design and Development of Neomycin Sulfate Gel Loaded with Solid Lipid Nanoparticles for Buccal Mucosal Wound Healing.

Drug administration to the wound site is a potential method for wound healing. The drug retention duration should be extended, and drug permeability through the buccal mucosal layer should be regulated. Oral wounds can be caused by inflammation, ulcers, trauma, or pathological lesions; if these wounds are not treated properly, they can lead to pain, infection, and subsequent undesirable scarring. This study aimed to develop Kolliphor-407 P-based gel containing neomycin sulfate (NES) loaded in solid lipid nanoparticles (SLNs) and enhance the antimicrobial activity. By considering lipid concentrations and achieving the lowest particle size (Y1) and maximum entrapment (EE-Y2) effectiveness, the formulation of NES-SLN was optimized using the Box-Behnken design. For the selected responses, 17 runs were formulated (as anticipated by the Design-Expert software) and evaluated accordingly. The optimized formulation could achieve a particle size of 196.25 and EE of 89.27% and was further utilized to prepare the gel formulation. The NES-SLN-G formula was discovered to have a smooth, homogeneous structure and good mechanical and rheological properties. After 24 h of treatment, NES-SLN-G showed a regulated in vitro drug release pattern, excellent ex vivo permeability, and increased in vitro antibacterial activity. These findings indicate the potential application of NES-SLN-loaded gels as a promising formulation for buccal mucosal wound healing.

Pairing 3D-Printing with Nanotechnology to Manage Metabolic Syndrome.

Introduction: This work was aimed to develop a Curcuma oil-based self-nanoemulsifying drug delivery system (SNEDDS) 3D-printed polypills containing glimepiride (GMD) and rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes as a model for metabolic syndrome (MS). Methods: Compartmentalized 3D printed polypills were prepared and studied in streptozotocin/poloxamer induced diabetic/dyslipidemic rats. The pharmacokinetic parameters of GMD and RSV in the prepared polypills were evaluated. Blood glucose level, lipid profile, antioxidant, and biochemical markers activities were investigated. Also, histopathological examination of the liver and pancreas was carried out. The atherosclerotic index, the area of islets of Langerhans, and liver steatosis lesion scores were calculated. Results: The developed SNEDDS-loaded GMD/RSV polypills showed acceptable quality control characteristics with a high relative bioavailability of 217.16% and 224.28% for GMD and RSV, respectively, when compared with the corresponding non-SNEDDS pills. The prepared polypills showed dramatic lowering in blood glucose levels and substantial improvement in lipid profile and hepatic serum biomarkers as well as remarkable decrease in serum antioxidants in response to Poloxamer 407 intoxication. The prepared polypills decreased the risk of atherosclerosis and coronary disease by boosting the level of high-density lipoprotein and lowering both triglyceride and low-density lipoprotein. Microscopic examination showed normal hepatic sinusoids and high protection level with less detectable steatosis in the examined hepatocytes. Normal size pancreatic islets with apparently normal exocrine acini and pancreatic duct were also noticed. Conclusion: This formulation strategy clearly shows the potential of the developed polypills in personalized medicine for treatment of patients with MS.

Repurposing Lovastatin Cytotoxicity against the Tongue Carcinoma HSC3 Cell Line Using a Eucalyptus Oil-Based Nanoemulgel Carrier.

Tongue cancer is one of the most common carcinomas of the head and neck region. The antitumor activities of statins, including lovastatin (LV), and the essential oil of eucalyptus (Eu oil), have been adequately reported. The aim of this study was to develop a nanoemulgel containing LV combined with Eu oil that could then be made into a nanoemulsion and assessed to determine its cytotoxicity against the cell line human chondrosarcoma-3 (HSC3) of carcinoma of the tongue. An I-optimal coordinate-exchange quadratic mixture design was adopted to optimize the investigated nanoemulsions. The droplet size and stability index of the developed formulations were measured to show characteristics of the nanoemulsions. The optimized LV loaded self-nanoemulsifying drug delivery system (LV-Eu-SNEDDS) was loaded into the gelling agent Carbopol 934 to develop the nanoemulgel and evaluated for its rheological properties. The cytotoxic efficiency of the optimized LV-Eu-SNEDDS loaded nanoemulgel was tested for cell viability, and the caspase-3 enzyme test was used against the HSC3 cell line of squamous carcinoma of the tongue. The optimized nanoemulsion had a droplet size of 85 nm and a stability index of 93%. The manufactured nanoemulgel loaded with the optimum LV-Eu-SNEDDS exhibited pseudoplastic flow with thixotropic behavior. The developed optimum LV-Eu-SNEDDS-loaded nanoemulgel had the best half-maximal inhibitory concentration (IC50) and caspase-3 enzyme values of the formulations developed for this study, and these features improved the ability of the nanoemulsion-loaded gel to deliver the drug to the investigated target cells. In addition, the in vitro cell viability studies revealed the synergistic effect between LV and Eu oil in the treatment of tongue cancer. These findings illustrated that the LV-Eu-SNEDDS-loaded gel formulation could be beneficial in the local treatment of tongue cancer.

Preparation and optimization of aloe ferox gel loaded with Finasteride-Oregano oil nanocubosomes for treatment of alopecia.

Alopecia areata is a skin disorder characterized by scarless, localized hair loss that is usually managed by topical treatments that might further worsen the condition. Therefore, the current study aimed to develop nano-cubosomes loaded with finasteride (FI) and oregano oil (Or) to improve drug solubility and permeation through skin and then incorporate it into an aloe ferox gel base. An l-optimal coordinate exchange design was adopted to optimize nano-cubosomes. Phytantriol and Alkyl Acrylate were employed as the lipid material, and surfactant respectively for cubosomes manufacture. The produced formulations were assessed for their particle size, entrapment efficiency (EE%), FI steady-state flux (Jss) and minimum inhibitory concentration (MIC) against Pro-pionibacterium acnes. Optimal FI-Or-NCu had a particle size of 135 nm, EE% equals 70%, Jss of 1.85 µg/cm2.h, and MIC of 0.44 µg/ml. The optimum formulation loaded gel gained the highest drug release percent and ex vivo skin permeation compared to FI aqueous suspension, and pure FI loaded gel. Aloe ferox and oregano oil in the optimized gel formulation had a synergistic activity on the FI permeation across the skin and against the growth of p. acne bacteria which could favor their use in treating alopecia. Thus, this investigation affirms the ability of FI-Or-NCu loaded aloe ferox gel could be an effective strategy that would enhance FI release and permeation through skin and maximize its favorable effects in treating alopecia.

Preparation and Optimization of Garlic Oil/Apple Cider Vinegar Nanoemulsion Loaded with Minoxidil to Treat Alopecia.

Alopecia areata is a scarless, localized hair loss disorder that is typically treated with topical formulations that ultimately only further irritate the condition. Hence, the goal of this study was to develop a nanoemulsion with a base of garlic oil (GO) and apple cider vinegar (APCV) and loaded with minoxidil (MX) in order to enhance drug solubilization and permeation through skin. A distance coordinate exchange quadratic mixture design was used to optimize the proposed nanoemulsion. Span 20 and Tween 20 mixtures were used as the surfactant, and Transcutol was used as the co-surfactant. The developed formulations were characterized for their droplet size, minoxidil steady-state flux (MX Jss) and minimum inhibitory concentration (MIC) against Propionibacterium acnes. The optimized MX-GO-APCV nanoemulsion had a droplet size of 110 nm, MX Jss of 3 µg/cm2 h, and MIC of 0.275 µg/mL. The optimized formulation acquired the highest ex vivo skin permeation parameters compared to MX aqueous dispersion, and varying formulations lacked one or more components of the proposed nanoemulsion. GO and APCV in the optimized formulation had a synergistic, enhancing activity on the MX permeation across the skin membrane, and the percent permeated increased from 12.7% to 41.6%. Finally, the MX-GO-APCV nanoemulsion followed the Korsmeyer-Peppas model of diffusion, and the value of the release exponent (n) obtained for the formulations was found to be 1.0124, implying that the MX permeation followed Super case II transport. These results demonstrate that the MX-GO-APCV nanoemulsion formulation could be useful in promoting MX activity in treating alopecia areata.

Investigation of Isocitrate Dehydrogenase 1 and 2 Mutations in Acute Leukemia Patients in Saudi Arabia.

Different forms of human cancer show mutations for isocitrate dehydrogenases 1 and 2 (IDH1/2). Mutation of these genes can cause aberrant methylation of the genome CpG islands (CGIs), which leads to an increase of suppressed oncogenes transcription or repression of active tumor suppressor gene transcription. This study aimed to identify the prevalence of IDH1/2 mutations in acute leukemia patients. The study cohort included 43 AML patients and 30 childhood ALL patients, from whom DNA bone marrow samples were taken. The alteration hotspots in codons IDH1 (R132) and IDH2 (R172 and R140) were examined via direct sequencing. Mutations in IDH1 were detected in 7 out of 43 (16.2%) AML patients; 5 of them occurred at codon R132. The other two mutations included a single-nucleotide polymorphism, which affected codon G105 in one patient. However, no mutation was detected in the IDH2 in any of the patients. Moreover, no mutations were detected in either IDH1 or IDH2 in ALL patients. The dominance of IDH1 mutations in AML, which was 16%, emphasizes the existence of the mutation in our population. On the other hand, IDH2 mutation was observed to be less frequent in both illnesses. Due to the limitation of using a small sample size, larger cohort screening is recommended to determine their usefulness as prognostic indicators.

Nanoemulsions: Formulation, characterization, biological fate, and potential role against COVID-19 and other viral outbreaks.

Viral diseases are emerging as global threats. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), that causes coronavirus disease (COVID-19), has severe global impacts. Safety, dosage, and potency of vaccines recently approved for emergency use against SARS-CoV-2 need further evaluation. There is still no effective treatment against COVID-19; therefore, safe, and effective vaccines or therapeutics against SARS-CoV-2 are urgently needed. Oil-in-water nanoemulsions (O/W NEs) are emerging as sophisticated, protective, and therapeutic platforms. Encapsulation capacity, which offers better drug pharmacokinetics, coupled with the tunable surfaces present NEs as promising tools for pharmaceutical applications. The challenges facing drug discovery, and the advancements of NEs in drug delivery demonstrate the potential of NEs against evolving diseases, like COVID-19. Here we summarize current COVID-19 knowledge and discuss the composition, stability, preparation, characterization, and biological fate of O/W NEs. We also provide insights into NE structural-functional properties that may contribute to therapeutic or preventative solutions against COVID-19.

Development of Multi-Compartment 3D-Printed Tablets Loaded with Self-Nanoemulsified Formulations of Various Drugs: A New Strategy for Personalized Medicine.

This work aimed to develop a three-dimensional printed (3DP) tablet containing glimepiride (GLMP) and/or rosuvastatin (RSV) for treatment of dyslipidemia in patients with diabetes. Curcumin oil was extracted from the dried rhizomes of Curcuma longa and utilized to develop a self-nanoemulsifying drug delivery system (SNEDDS). Screening mixture experimental design was conducted to develop SNEDDS formulation with a minimum droplet size. Five different semi-solid pastes were prepared and rheologically characterized. The prepared pastes were used to develop 3DP tablets using extrusion printing. The quality attributes of the 3DP tablets were evaluated. A non-compartmental extravascular pharmacokinetic model was implemented to investigate the in vivo behavior of the prepared tablets and the studied marketed products. The optimized SNEDDS, of a 94.43 ± 3.55 nm droplet size, was found to contain 15%, 75%, and 10% of oil, polyethylene glycol 400, and tween 80, respectively. The prepared pastes revealed a shear-thinning of pseudoplastic flow behavior. Flat-faced round tablets of 15 mm diameter and 5.6-11.2 mm thickness were successfully printed and illustrated good criteria for friability, weight variation, and content uniformity. Drug release was superior from SNEDDS-based tablets when compared to non-SNEDDS tablets. Scanning electron microscopy study of the 3DP tablets revealed a semi-porous surface that exhibited some curvature with the appearance of tortuosity and a gel porous-like structure of the inner section. GLMP and RSV demonstrated relative bioavailability of 159.50% and 245.16%, respectively. Accordingly, the developed 3DP tablets could be considered as a promising combined oral drug therapy used in treatment of metabolic disorders. However, clinical studies are needed to investigate their efficacy and safety.

Impact of Site-Specific Bioconjugation on the Interfacial Activity of a Protein Biosurfactant.

Biosurfactants are surface active molecules that can be produced by renewable, industrially scalable biologic processes. DAMP4, a designer biosurfactant, enables the modification of interfaces via genetic or chemical fusion to functional moieties. However, bioconjugation of addressable amines introduces heterogeneity that limits the precision of functionalization as well as the resolution of interfacial characterization. Here, we designed DAMP4 variants with cysteine point mutations to allow for site-specific bioconjugation. The DAMP4 variants were shown to retain the structural stability and interfacial activity characteristic of the parent molecule, while permitting efficient and specific conjugation of polyethylene glycol (PEG). PEGylation results in a considerable reduction on the interfacial activity of both single and double mutants. Comparison of conjugates with one or two conjugation sites shows that both the number of conjugates as well as the mass of conjugated material impact the interfacial activity of DAMP4. As a result, the ability of DAMP4 variants with multiple PEG conjugates to impart colloidal stability on peptide-stabilized emulsions is reduced. We suggest that this is due to steric constraints on the structures of amphiphilic helices at the interface. Specific and efficient bioconjugation permits the exploration and investigation of the interfacial properties of designer protein biosurfactants with molecular precision. Our findings should therefore inform the design and modification of biosurfactants for their increasing use in industrial processes and nutritional and pharmaceutical formulations.

Nanoemulsions in drug delivery: formulation to medical application.

Nanoscale oil-in-water emulsions (NEs), heterogeneous systems of two immiscible liquids stabilized by emulsifiers or surfactants, show great potential in medical applications because of their attractive characteristics for drug delivery. NEs have been explored as therapeutic carriers for hydrophobic compounds via various routes of administration. NEs provide opportunities to improve drug delivery via alternative administration routes. However, deep understanding of the NE manufacturing and functionalization fundamentals, and how they relate to the choice of administration route and pharmacological profile is still needed to ease the clinical translation of NEs. Here, we review the diversity of medical applications for NEs and how that governs their formulation, route of administration, and the emergence of increasing sophistication in NE design for specific application.