Low Polydispersity Index Values Research Articles

Comparative Study of Lycopene-Loaded Niosomes Prepared by Microfluidic and Thin-Film Hydration Techniques for UVB Protection and Anti-Hyperpigmentation Activity.

Niosomes are employed for their improved physical properties and stability and as a controlled delivery system. However, their large-scale production and different preparation methods affect their physical properties. The microfluidic method represents a novel approach to the preparation of niosomes that enables precise control and decreases the preparation time and steps compared to alternative methods. The UVB protection and anti-hyperpigmentation activities of lycopene-loaded niosomes prepared by microfluidic (MF) and novel conventional thin-film hydration (THF) methods were compared. Extract powders from tomatoes (T), carrots (C), and mixed red vegetables (MR) were utilized to prepare lycopene-rich extract-entrapped niosomes. The resulting niosome formulations were characterized by particle size, polydispersity index (PDI), zeta potential, FT-IR spectra, entrapment efficiency, lycopene-release profile, permeation, and stability. The lycopene extract-niosome formulations were evaluated for their potential to provide UVB protection to human keratinocytes (HaCaT) and for their anti-melanogenesis effects on B16F10 melanoma cells. The results indicated that niosomes prepared by the MF method exhibited high uniformity and homogeneity (reflected by a low PDI value) and maintained smaller sizes when processed through a chip utilizing a hydrodynamic flow-focusing (HFF) platform compared to THF niosomes. The release kinetics of all lycopene-niosome formulations followed the Korsmeyer-Peppas model. The FT-IR spectra indicated that lycopene was incorporated into the niosome bilaminar membrane. Moreover, niosomes obtained from MF demonstrated enhanced stability during heating-cooling cycles, along with high UVB protection and anti-melanogenesis effects. Therefore, these developed niosome preparation methods could be effectively applied to topical products.

A structural, magnetic and colloidal stability study of uncoated and silica coated iron oxide samples prepared in two different surfactants

The discovery of new magnetic materials of interest in the biomedicine field is a relevant topic in current research. For years, our research group has been investigating the obtaining and study of nanostructured magnetic samples that behave superparamagnetically to enable their transport in living organisms. We present here a study that summarizes the structural characteristics, magnetic behavior and stability of two Fe3O4 samples synthesized by coprecipitation that were dispersed using two different surfactants (oleylamine, OL, and oleic acid, OA), and two others prepared from the previous ones by reaction with tetraethyl orthosilicate (TEOS). The relationships between the surfactant used in the synthesis, the presence of a certain maghemite (γ-Fe2O3) content, the influence of silica shell thickness and magnetic behaviour of all samples were systematically studied by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), Mössbauer spectroscopy and H vs. M loops. Rietveld refinements of the XRD profiles confirmed a partial oxidation of the non-silica-coated samples and FTIR spectra of the uncoated samples showed a very strong broad metal-oxygen band and additional sets of bands from the different organic chains of the two surfactants. Individual particles with a mean diameter of 7 and 9 nm were distinguished in TEM images of uncoated magnetic samples. Mössbauer data indicated the presence of non-stoichiometric magnetite in all samples, in agreement with XRD refinements. Magnetic measurements confirmed the superparamagnetic behavior of all the samples. Highest negative zeta potential values are found for the silica covered samples in both acidic and basic medium, being Fe3O4-AO@SiO2 the best suited for the purposes of its dispersibility in future applications. Low polydispersity index (PDI) values confirmed the best stability and dispersibility of all samples investigated in tetrahydrofuran (THF).

An Integrated and Modular Compartmentalized Microfluidic System with Tunable Electrospun Porous Membranes for Epithelialized Organs-on-a-Chip.

A modular and 3D compartmentalized microfluidic system with electrospun porous membranes (PMs) for epithelialized organ-on-a-chip systems is presented. Our novel approach involves direct deposition of polymer nanofibers onto a patterned poly(methyl methacrylate) (PMMA) substrate using electrospinning, resulting in an integrated PM within the microfluidic chip. The in situ deposition of the PM eliminates the need for additional assembly processes. To demonstrate the high throughput membrane integration capability of our approach, we successfully deposited nanofibers onto various chip designs with complex microfluidic planar structures and expanded dimensions. We characterized and tested the fully PMMA chip by growing an epithelial monolayer using the Caco-2 cell line to study drug permeability. A comprehensive analysis of the bulk and surface properties of the membrane's fibers made of PMMA and polystyrene (PS) was conducted to determine the polymer with the best performance for cell culture and drug transport applications. The PMMA-based membrane, with a PMMA/PVP ratio of 5:1, allowed for the fabrication of a uniform membrane structure along the aligned nanofibers. By modulating the fiber diameter and total thickness of the membrane, we could adjust the membrane's porosity for specific cell culture applications. The PMMA-PVP nanofibers exhibited a low polydispersity index value, indicating monodispersed nanofibers and a more homogeneous and uniform fiber network. Both types of membranes demonstrated excellent mechanical integrity under medium perfusion flow rates. However, the PMMA-PVP composition offered a tailored porous structure with modulable porosity based on the fiber diameter and thickness. Our developed platform enables dynamic in vitro modeling of the epithelial barrier and has applications in drug transport and in vitro microphysiological systems.

Green and chemical synthesized zinc oxide nanoparticles: Evaluation of their anti-proliferative activity against breast cancer cell line – An in vitro and in silico approach

Zinc Oxide nanoparticles (ZnO NPs) were synthesized through both chemical and green approaches using wheat grass (WG) extract. Characterization techniques included Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM) with Energy-Dispersive X-ray Spectroscopy (EDX), Fourier-transform infrared Spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), and Ultraviolet-visible (UV-Vis) spectroscopy. CS-ZnO NPs and WG-ZnO NPs exhibited characteristic surface plasmon resonance (SPR) peaks at 360 nm and 320 nm, respectively, with low polydispersity index (PDI) values indicating uniform nanoparticle dispersion. FTIR analysis revealed distinct functional groups on the ZnO NPs’ surface for stabilization. XPS confirmed atomic composition and oxidation state, while XRD confirmed their hexagonal wurtzite structure. SEM images revealed rod-shaped structures, supported by EDX analysis confirming ZnO NP formation through elemental content. The synthesized ZnO NPs demonstrated significant cytotoxicity against MDA-MB 231 breast cancer cells, causing changes in nuclear morphology, increased reactive oxygen species levels, and membrane damage. Wound healing assay highlighted their potential in inhibiting cancer metastasis. Molecular docking between WG compounds and breast cancer targets revealed that the enhanced efficacy of green-synthesized ZnO NPs could be attributed to covalent linkage of active molecules of WG onto the nanoparticle surface. Overall, ZnO NPs synthesized using the green method outperformed their chemically synthesized counterparts.

Extension of ultrafiltered cheese shelf life using edible coatings containing supercritical rosemary, thyme and coriander extracts as antimicrobial agents

Currently, supercritical extraction allows for the “green” isolation of plant antimicrobial components and their subsequent use in the food industry. The study aims to extend the shelf life of ultrafiltered cheese by using edible coatings containing supercritical fluid extracts (SFEs) of Rosmarinus officinalis L., Thymus vulgaris and Coriandrum sativum L. The SFEs chemical profiling was studied using GC-MS. Ten emulsion coating formulations were prepared using whey protein concentrate and the SFEs. The antimicrobial activity of coatings was assessed using well diffusion assay. Their effect on shelf life, physicochemical and sensory characteristics of the ultrafiltered cheese samples was investigated. GC/MS analysis of Rosmarinus officinalis L., Thymus vulgaris and Coriandrum sativum L. showed that 1,8-Cineol, m-Cymene, and Linalool are the major compounds with 35.4, 41.6, and 61.3 % respectively. The particle size of all formulations ranged from 157.3 to 453.7 nm and had a broad size distribution with a low Polydispersity Index values ranging from 0.35 to 0.49. The obtained Zeta potential values from −27.8 to −36.0 mV indicate the stability of the SFE-emulsion formulations. The antimicrobial trials showed that formulations, that mainly contained Thymus vulgaris, demonstrated more inhibition effect against all tested strains than other formulas with inhibition zone diameter ranged between 10.7 and 16.3 mm and followed by formulations, that mainly contained Rosmarinus officinalis L., with inhibition zones diameter between 6.7 and 11.7 mm depending on microbial type. Combining rosemary and coriander extracts synergistically enhanced their antimicrobial effect and extended the shelf life of cheese beyond 40 days.

Hyaluronic acid/chitosan-coated poly (lactic-co-glycolic acid) nanoparticles to deliver single and co-loaded paclitaxel and temozolomide for CD44+oral cancer cells

Oral cancer has a poor survival rate despite comprehensive therapy. Current treatments result in acute side effects and fail to eliminate an aggressive group of cells overexpressing CD44. Such cells are capable of tumour initiating, self-renewal, invasion and metastasis, resulting in tumour relapse and resistance. This study aims to synthesise and characterise hyaluronic acid/chitosan-coated poly (lactic-co-glycolic acid) nanoparticles and assess their effectiveness in delivering Paclitaxel and Temozolomide to human tongue squamous cell carcinoma cell line that expresses high CD44 levels, in terms of cell cytotoxicity and apoptosis. This study also assesses the coordinated administration of Paclitaxel and Temozolomide and whether they exhibit significant synergistic cell inhibition effects with reduced introduced drug concentration if co-delivered simultaneously. Nanoparticles were synthesised with solvent evaporation method and characterised to assess their size, homogeneity, and zeta potential. Cell viability assay and real-time cell analysis were performed to examine the cell inhibitory effect of the drug-loaded nanoparticles. Cell apoptosis and cell cycle alteration were detected, and reactive oxygen species induction, mitochondrial membrane potential, and expressed genes associated with cell inhibition and death were evaluated. The synthesised nanoparticles had a nano-sized diameter of 260.40±11.54 nm, a positive zeta potential of +14.31±1.37 mV and a low polydispersity index value of 0.15±0.03. Paclitaxel, Temozolomide, and their combination have inhibited cell proliferation with half maximal inhibitory concentrations of 4 nM, 1000 μM and 2nM:300 μM, respectively. Compared to free drugs, the single-loaded and co-loaded drugs induced more cytotoxicity. Paclitaxel and Temozolomide showed a considerable synergistic inhibitory effect which was discovered to be more significant when the drugs were loaded in the nanoparticles. Drug-loaded nanoparticles were verified to induce higher cell apoptosis rates, cell proportion arrested at the S-phase of the cell cycle, reactive oxygen species generation, mitochondrial collapse and expression of genes associated with cellular inhibition and death than free drugs. These results demonstrate that the established nanoparticles could be a potential candidate for oral cancer therapy since they could deliver and improve the efficacy of single and dual drugs against oral cancer cells.

PH-Responsive Poly(ethylene glycol)-b-poly(2-vinylpyridine) Micelles for the Triggered Release of Therapeutics

The use of pH-responsive polymeric micelles is a promising approach to afford the targeted, pH-mediated delivery of hydrophobic drugs within the low-pH tumour milieu and intracellular organelles of cancer cells. However, even for a common pH-responsive polymeric micelle system-e.g., those utilising poly(ethylene glycol)-b-poly(2-vinylpyridine) (PEG-b-PVP) diblock copolymers-there is a lack of available data describing the compatibility of hydrophobic drugs, as well as the relationships between copolymer microstructure and drug compatibility. Furthermore, synthesis of the constituent pH-responsive copolymers generally requires complex temperature control or degassing procedures that limit their accessibility. Herein we report the facile synthesis of a series of diblock copolymers via visible-light-mediated photocontrolled reversible addition-fragmentation chain-transfer polymerisation, with a constant PEG block length (90 repeat units (RUs)) and varying PVP block lengths (46-235 RUs). All copolymers exhibited narrow dispersity values (Đ ≤ 1.23) and formed polymeric micelles with low polydispersity index (PDI) values (typically <0.20) at physiological pH (7.4), within a suitable size range for passive tumour targeting (<130 nm). The encapsulation and release of three hydrophobic drugs (cyclin-dependent kinase inhibitor (CDKI)-73, gossypol, and doxorubicin) were investigated in vitro at pH 7.4-4.5 to simulate drug release within the tumour milieu and cancer cell endosome. Marked differences in drug encapsulation and release were observed when the PVP block length was increased from 86 to 235 RUs. With a PVP block length of 235 RUs, the micelles exhibited differing encapsulation and release properties for each drug. Minimal release was observed for doxorubicin (10%, pH 4.5) and CDKI-73 exhibited moderate release (77%, pH 4.5), whereas gossypol exhibited the best combination of encapsulation efficiency (83%) and release (91% pH 4.5) overall. These data demonstrate the drug selectivity of the PVP core, where both the block molecular weight and hydrophobicity of the core (and accordingly the hydrophobicity of the drug) have a significant effect on drug encapsulation and release. These systems remain a promising means of achieving targeted, pH-responsive drug delivery-albeit for select, compatible hydrophobic drugs-which warrants their further investigation to develop and evaluate clinically relevant micelle systems.

Green Nanoemulsion Water/Ethanol/Transcutol/LabM-Based Treatment of Pharmaceutical Antibiotic Erythromycin-Contaminated Aqueous Bulk Solution.

Contaminated wastewater released from hospital, domestic, and industrial sources is a major challenge to aquatic animals and human health. In this study, we addressed removal of erythromycin (ERN) from contaminated water employing water/ethanol/Transcutol/Labrafil M 1944 CS (LabM) green nanoemulsions as a nanocarrier system. ERN is a major antibiotic contaminant harming aquatic and human lives. Green nanoemulsions were prepared and evaluated for size, size distribution (measuring polydispersity index), stability, zeta potential, refractive index, and viscosity. Transmission electron microscopy (TEM) was used to visualize morphological behavior. The treated-water was analyzed for ERN by the spectroscopy, scanning electron microscopy-energy-dispersive X-ray analysis mode (SEM-EDX), and inductively coupled plasma-optical emission spectroscopy (ICP-OES) techniques. We studied factors (composition, size, viscosity, and time of exposure) affecting removal efficiency (%RE). The obtained green nanoemulsions (ENE1-ENE5) were stable and clear (<180 nm). ENE5 had the smallest size (58 nm), a low polydispersity index value (0.19), optimal viscosity (∼121.7 cP), and a high negative zeta potential value (-25.4 mV). A high %RE value (98.8%) was achieved with a reduced size, a high water amount, a low Capryol 90 content, and optimal viscosity as evidenced by the obtained results. Moreover, contact time had insignificant effect on %RE. UV-vis spectroscopy, SEM-EDX, and ICP-OES confirmed the absence of ERN from the treated water. Conclusively, ERN can easily be removed from polluted water employing green nanoemulsions prepared from the optimized excipients, and evaluated characteristics.

Transferrin-Functionalized Liposomes for the Delivery of Gallic Acid: A Therapeutic Approach for Alzheimer's Disease.

Senile plaques composed of amyloid β (Aβ) fibrils are considered the leading cause of Alzheimer’s disease (AD). Molecules with the ability to inhibit Aβ aggregation and/or promote Aβ clearance are thus a promising approach for AD therapy. Our group recently demonstrated that gallic acid (GA) has strong anti-amyloidogenic properties. In this study, stealth liposomes were prepared for the delivery of GA for AD therapy. The liposomes were functionalized with transferrin (Tf) to direct them to the brain, since Tf receptors are overexpressed in the endothelial cells of the blood–brain barrier. GA-loaded Tf-functionalized liposomes showed mean diameters of 130 nm, low polydispersity index values, and neutral zeta potential. Moreover, the produced nanocarriers promoted the sustained release of GA over 5 days and are physically stable for 1 month under storage conditions. Furthermore, GA-loaded Tf-functionalized liposomes showed a strong ability to interact with Aβ1-42 monomers, slowing down the Aβ monomer-to-oligomer and oligomer-to-fibril transitions and decreasing the number of fibrils formed by 56%. In addition, the NPs disaggregated approximately 30% of preformed Aβ fibrils. The presented results suggest that Tf-functionalized liposomes could be a viable platform for the brain delivery of GA for AD therapy. Studies with animal models of AD will be valuable for validating the therapeutic efficacy of this novel liposomal formulation.

Nanophytosomes as a protection system to improve the gastrointestinal stability and bioavailability of phycocyanin

Nano-phytosomes (NP), lipid-based nano-carriers, were used to encapsulate the phycocyanin. Phycocyanin (Phy) is known for its important biological properties with low bioavailability and low stability. The aim of the study was to prepare phosphatidylcholine (PC) based Phy loaded NP to overcome the bioavailability and storage stability issues. The characterization of NP such as entrapment efficiency (EE), particle size, poly-dispersity index (PDI), ζ-potential and microstructural properties was conducted and in vitro bioaccessibility and storage stability of bioactive properties were investigated. The highest EE was determined as 81.92% however with a loading capacity (LC) of 58.12%. Phy-NPs showed good characteristics, such as low PDI values (<0.5), low particle size (106.13–134.10 nm), and non-dense spherical shape of microstructure. All NP complexes showed significant bioaccessibility with total phenolic content (TPC) values greater than 50% in intestinal tract. Unfortunately, PC based NP did not show a clear-cut pattern of TPC and color protection of Phy via increased PC content.

DESIGN OF TEA TREE OIL-LOADED NANOSTRUCTURED LIPID CARRIERS: PREPARATION AND IN VITRO ANTIFUNGAL ACTIVITY

Tea tree oil (TTO) is a promising essential oil that has enormous potential for antifungal development. However, its pharmacological applications have several limitations, including volatility and an extensive range of partition coefficients. To overcome these, TTO can be loaded into a nanostructured lipid carrier (NLC). The combination of solid and liquid lipids and production conditions affect the characteristics of the NLC formed. This study aimed to design TTO-loaded NLCs with appropriate particle sizes to improve the therapeutic efficacy of TTO as an antifungal agent. The novelty of this research is the discovery of a stable and potential TTO loaded NLC formula as a topical antifungal agent. TTO-loaded NLCs were prepared using the high-shear homogenization method with formulas consisting of TTO, solid lipids, liquid lipids, surfactants, and distilled water. Then, they were characterized with particular attention to average particle size, polydispersity, zeta potential, pH, and viscosity. Further tests included physical stability for one month at room temperature (27±2 °C) and in vitro antifungal activity using the well diffusion method. TTO-loaded NLCs combining stearic acid, glyceryl monostearate, and cetyl alcohol (solid lipids) with Miglyol 812 and olive oil (liquid lipids) showed relatively small average particle sizes and low polydispersity index values. Also, the stirring speed did not affect the particle size. It was found that TTO exhibited in vitro antifungal activities as good as ketoconazole cream. This study has successfully combined various solid and liquid lipids to formulate TTO-loaded NLCs with favorable stability for one-month storage and great antifungal potential.

Characterization And Cytotoxicity of Novel Synthesis Selenium Nanoparticles Stabilized By Vitamin E TPGS

The aim of this research was to investigate synergistic effect of combination two related antioxidant agents by novel synthesis of selenium nanoparticles functionalized with D-α- Tocopherol polyethylene glycol 1000 succinate (TPGS) as a capping agent during chemical reduction of sodium selenite by ascorbic acid. Particle size, morphology, crystallite size of synthesized Se-TPGS were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), Ultraviolet-Visible spectrophotometry (UV/Vis), X-Ray diffraction (XRD). The in vitro antioxidant activity, cell toxicity and blood compatibility assays were investigate respectively. The DLS results revealed that the Se-TPGS possess very low polydispersity index value (PDI = 0.03) and having hydrodynamic particle size of 83.33 ± 14.7 nm with negatively value for zeta potential equal to -19.5 mV. Both SEM and TEM show regular spherical shape of SeNPs with size measurement less than DLS measuring. XRD result confirming that the produced SeNPs possessed a standard crystalline hexagonal phase structure. DPPH assay of total antioxidant activity display high antioxidant activity of Se-TPGS NPs when comparing with ascorbic acid as a reference material. The cytotoxicity of new formula Se-TPGS investigated for both cancerous (MCF-7) and normal (HBL-100) breast cell lines with significantly different. This study provides a facile and green method for chemically synthesizing stable SeNPs which are suitable for further evaluation in therapeutic applications. The SeNPs could be a blueprint in the field of biomedical application as an alternative chemotherapy for fighting cancerous cells.

Synthesis of large and stable colloidal gold nanoparticles (AuNPs) by seeding-growth method

Colloidal gold nanoparticles (AuNPs) have been used in various applications, mainly in biomedical sciences for therapeutic and diagnostic purposes. These AuNPs can be conjugated with biomolecules and chemical substances due to their unique physical and chemical properties. The AuNPs are usually synthesized by a chemical method; namely Turkevich method or reduction method. However, this synthesis method is not suitable for synthesis of large AuNPs due to aggregation and instability of AuNPs suspension. Thus, the aim for this study is to evaluate the seeding-growth method for synthesis of large AuNPs. The seed of 15 nm AuNPs was initially produced using the citrate reduction method, then further grown to 40, 60, and 80 nm AuNPs using the mild reduction agent, hydroxylamine. Transmission electron microscopy (TEM), dynamic light scattering (DLS), and UV–vis- NIR spectroscopy were used to characterize the as-synthesized AuNPs. The narrow particle size distribution and low polydispersity index value (PDI) for all AuNPs revealed the presence of monodisperse AuNPs. The as-synthesized AuNPs are nearly spherical as shown by the degree of ellipticity (G) close to 1.00. This result showed no agglomeration of AuNPs in the colloidal suspension. The UV–vis-NIR spectra showed peaks shifted to a longer wavelength that confirmed increasing size of AuNPs. The synthesis of different sizes of AuNPs using the seeding-growth method was successful and stable with no aggregation and agglomeration.

Phytosynthesis of Silver Nanoparticles Using Perilla frutescens Leaf Extract: Characterization and Evaluation of Antibacterial, Antioxidant, and Anticancer Activities

PurposeThe present study investigates the phytosynthesis of silver nanoparticles (AgNPs) using Perilla frutescens leaf extract, which acts as a reducing agent for the conversion of silver ions (Ag+) into AgNPs. P. frutescens leaf synthesized AgNPs (PF@AgNPs) were evaluated for biomedical properties including antibacterial, antioxidant and anticancer activities.Materials and MethodsPF@AgNPs were synthesized using P. frutescens leaf extract and silver nitrate solution. The morphology and physical properties of PF@AgNPs were studied by spectroscopic techniques including, UV-Vis, FTIR, TEM, XRD, DLS, and TGA. Antibacterial activity of PF@AgNPs was evaluated by disk diffusion assay. Antioxidant activity of PF@AgNPs was checked by 2.2-diphenyl-1-picrylhydrazyl (DPPH), and 2.2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging assays. Anticancer activity of PF@AgNPs was checked by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Cytotoxic effects of PF@AgNPs on most susceptible cancer cell lines were observed by phase contrast microscopy.ResultsPF@AgNPs showed surface plasmon resonance peak at 461 nm. XRD pattern showed that the PF@AgNPs were face-centered cubic crystals with a mean size of 25.71 nm. TEM analysis revealed the different shapes (spherical, rhombic, triangle, and rod) of PF@AgNPs. Zeta potential value (−25.83 mV) indicated that PF@AgNPs were long-term stable and not agglomerated. A low polydispersity index value (0.389) indicated the monodispersity of PF@AgNPs. TGA revealed the high thermal stability of PF@AgNPs. PF@AgNPs exhibited maximum inhibition against Escherichia coli, followed by Bacillus subtilis and Staphylococcus aureus. PF@AgNPs showed maximum inhibition of 68.02 and 62.93% against DPPH and ABTS-free radicals, respectively. PF@AgNPs showed significant anticancer activity against human colon cancer (COLO205) and prostate adenocarcinoma (LNCaP). PF@AgNPs exhibited apoptotic effects on LNCaP cells including cell shrinkage, membrane blebbing, chromatin condensation, fragmentation of nuclei, and formation of apoptotic bodies.ConclusionThe present study reports the successful synthesis of PF@AgNPs using P. frutescens leaf extract. The synthesized PF@AgNPs are FCC crystals, monodispersed, long-term stable, and non-agglomerated. The observed antibacterial, antioxidant, and anticancer activities demonstrate the potential biomedical applications of PF@AgNPs.

Dermal Delivery of Meloxicam Nanosuspensions based Gel: Optimization with Box Behnken Design Experiment Approach: Ex Vivo and In Vivo Study

Background: Transdermal delivery of meloxicam is advantageous than the oral route in the treatment of pain management. Objective: The goal of the present study is to formulate and evaluate meloxicam (MX) loaded nanosuspensions based gel for transdermal application. Methods: The formulation parameters were optimized using Box Behnken design (BBD) taking three independent variables and three responses. Formulations were evaluated for particle size (nm), polydispersity index (PDI), zeta potential (mV), ex vivo permeation, in vivo study, morphology, FTIR, skin irritation and, stability study. Optimized formulation having Poloxamer 188 (0.4 mg), PVP K30 (0.5 mg) and sonication time (60 min.) demonstrated smaller particle size (159.2 ± 3.5 nm), low PDI (0.120 ± 0.01) and higher zeta potential value (-29 ± 4mV). Results: In the ex vivo study, MX-NG showed a significant increase (p&lt;0.05) in the flux (24.40 ± 2.6 μg/cm2/h) of meloxicam through the human cadaver skin as compared to other formulations. In the in- vivo study, MX-NG showed a significant (p&lt;0.05) increase in anti-inflammatory activity as compared to marketed gel. Conclusion: Thus, it is concluded that the developed meloxicam loaded nanosuspensions based gel showed maximum therapeutic effects in rats.

Biodegradable Nanovectors As a Direct Platform for the Controlled Delivery of Chemotherapeutic Drugs Against Childhood ALL

Drugs used to treat childhood acute lymphoblastic leukemia (ALL), both clinically and experimentally, are often highly insoluble making drug delivery inefficient due to precipitation and poor distribution. Toxicity is also a major issue owing to the high levels of harmful solvents used to solubilize drugs for administration. Therefore, identifying strategies to enhance the stability and solubility of poorly soluble drugs is an ongoing challenge. Data from clinical trials indicates that the pharmacokinetics of dexamethasone (Dex), commonly used in induction regimens for ALL, vary considerably between patients (pts) and prolonging drug exposure rather than increasing absolute dose may improve efficacy. Copolymeric nanovectors (NV) are an excellent candidate for the delivery of insoluble drugs. However, despite reports of multiple systems, the fabrication processes often rely on complex methodologies with purification steps to remove harmful chemicals used to load drugs. To bypass these fabrication issues, we have shown that fully biodegradable copolymer NV comprised of poly(ethylene glycol)-block-poly (trimethylene carbonate) (PEG-PTMC) can sequester highly insoluble drugs (with almost total efficiency) through a direct hydration process in 5 minutes, eliminating the need for purification and use of harmful solvents. The aim of this study was to assess the effects of this systemin vitroandin vivousing Dex. NV were formulated with Dex or 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide (DiR, a near infrared insoluble dye) to model NV distributionin vivo. Both Dex and DiR solubilization was initiated using residual (&amp;lt;0.025%) amounts of dimethyl sulfoxide (DMSO) prior to addition to PEG-PTMC, oligo ethylene glycol and stirring into phosphate buffered saline. The average hydrodynamic radii of NV were ca. 40nm when loaded with Dex or DiR, as measured by dynamic light scattering. All formulations had low polydispersity index values (&amp;lt;0.18), indicating highly uniform monodispersed populations of NV. DiR-NV were optimised to 0.125wt% to give the best linearity in fluorescence signal (r2 = 0.97) over a wide range of copolymer concentrations (0.1-20 mg/ml).In vitro, Dex-NV were equipotent with free Dex (dispersed in medium with DMSO) against primary T-ALL cells from all pts tested. The highest dose (100 µM) reduced cell viability to 45±38% in Dex-NV and 46±40% in free Dex treated cells. Crucially, the NV formulation did not reduce Dex efficacy and confirmed our previous findings using parthenolide in this system. As a control, empty (unloaded) NV were not toxicin vitro. To assess the effects of NVin vivo, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were injected with primary ALL cells from 3 pts and engraftment was measured in peripheral blood (PB) aspirates using flow cytometry. Once engrafted (&amp;gt;0.1% ALL cells) animals were treated daily for 5 days, over 4 weeks with 2.5 mg/kg Dex via intraperitoneal injection (IP). Both Dex-NV and free Dex delayed disease progression until day 18 in pt 1, and until after treatment cessation in pts 2 and 3 with disease levels of 0.24±0.1% and 0.55±0.1% near the end of treatment, respectively. In contrast, leukemia engraftment increased immediately following engraftment in placebo controls. Dex-NV and free Dex significantly improved the survival of NSG by up to 27 days (P&amp;lt;0.01) with no significant differences between treatments. Ten minutes after intravenous injection (IV) with DiR-NV, ventral imaging showed that fluorescence was detected throughout NSG with accumulations in the bone marrow, lungs, liver, spleen and the head area, indicative of uniquely broad distribution properties. Peak fluorescence was also detected in PB aspirated from the opposite tail vein to that injected, from the first time point (452±225 RFU, 30 minutes). The half-life of DiR-NV in PB was 2.25 hours for IV treated mice. As expected, in IP treated mice fluorescence levels took longer to peak (2 hours, 138±83 RFU) and had a half-life of 3.2 hours from this point. In conclusion, these results demonstrate the usefulness of PEG-PTMC NV for the delivery and consequent retention of insoluble chemotherapeutic drugs; without hindering their performancein vitroorin vivo. The generated NV are biocompatible, do not require purification and can be fabricated within 5 minutes. These data support the testing of NV against more pt samplesin vivowith Dex and other insoluble drugs. Disclosures No relevant conflicts of interest to declare.

Antibacterial Activity of Chitosan Nanoparticles Against Pathogenic N. gonorrhoea.

PurposeThe emergence of Neisseria gonorrhoeae strains that are resistant to the most commonly used antibiotics represents a great concern for global public health. This challenges the effectiveness of clinical treatment regimens and demands the development of alternative antigonococcal agent. In this regard, chitosan nanoparticles (CNPs) are known to have antimicrobial activity against a wide range of pathogens. Thus, they have become a potential candidate for combatting this era of multi-drug resistance. This study aims to formulate CNPs, characterize their physicochemical properties, and examine their antimicrobial activity against gonococcus.Materials and MethodsThe ionic gelation method was used to prepare CNPs of different concentrations. Characterization for their particle size (PZ), polydispersity index (PDI), and zeta potential (ZP) was performed. The anti-microbial activity of CNPs was investigated against 13 WHO N. gonorrhoeae reference strains, using the broth dilution method. Cytotoxicity of CNPs and their effect on bacterial adhesion to HeLa cells were investigated.ResultsThe average PZ and ZP of the prepared NPs were increased when the concentration of chitosan was increased from 1 to 5 mg/mL and found to be in the range of 193 nm ± 1.9 to 530 nm ± 13.3, and 14 mV ± 0.5 to 20 mV ± 1, respectively. Transmission electron microscopes (TEM) images revealed spherical NPs, and the NPs had a low PDI value of ≤0.27. The formed CNPs produced antibacterial activity against all tested strains, including those resistant to multiple antibiotics, with a minimum inhibitory concentration (MIC90) of 0.16 to 0.31 mg/mL and a minimum bactericidal concentration (MBC) of 0.31 to 0.61 mg/mL. Of note, at all MIC90 and MBC, the CNPs had no significant cytotoxic effect on HeLa cells and reduced bacterial adhesion to these cells at MBC doses.ConclusionThe present work findings suggest the potential of the CNPs for the treatment of gonorrhoea.

Mercaptoalkanoic Acid‐Induced Band Gap Attenuation of Copper Selenide Quantum Dot

AbstractCopper selenide quantum dot (CuSeQD) materials functionalised with mercaptoalkanoic acids {3‐mercaptopropionic acid (3‐MPA), 6‐mercaptohexanoic acid (6‐MHA) and mercaptosuccinic acid (MSA)} were synthesized by a reproducible aqueous colloidal technique at room temperature. The impact of the capping agents on the size and the crystallinity of the CuSeQD materials, were investigated by small angle X‐ray scattering (SAXS) and X‐ray diffraction (XRD) spectroscopic techniques, respectively. SAXS results confirmed that 6‐MHA‐CuSeQD had the smallest average particle core size when dried, whereas MSA‐CuSeQD had the smallest size in aqueous solution, though with a tendency to aggregate. Dynamic light scattering (DLS) measurements indicated strong bonding of the capping agents to CuSe particles, with MSA being the weakest binding agent, as confirmed by comparatively, low Zeta potential(ζ=−31.1 mV) and high polydispersity index (0.469) values. UV‐Vis absorption studies confirmed a large blue shift of the band gap for the QD compared to the bulk material, with characteristic absorption band (λ) and direct band gap (Egd) values being (λ=435 nm, Egd=8.0 eV), (λ=400 nm, Egd=5.6 eV) and (λ=340 nm, Egd=4.0 eV), for 6‐MHA‐CuSeQD, 3‐MPA‐CuSeQD and MSA‐CuSeQD, respectively. As supported by the formal potential values for 6‐MHA‐CuSeQD (E0′≈120 mV), 3‐MPA‐CuSeQD (E0′≈159 mV) and MSA‐CuSeQD (E0′≈183 mV), the smaller the particle size, the lower the potential required for the application of the quantum dots in an electron transfer process.

Fabrication and characterization of zein/lactoferrin composite nanoparticles for encapsulating 7,8-dihydroxyflavone: Enhancement of stability, water solubility and bioaccessibility

7,8-dihydroxyflavone (7,8-DHF), a tyrosine kinase B (TrkB) receptor agonist, can mimick physiological actions of brain-derived neurotrophic factor (BDNF) to attenuate neurogenic disease. However, its use as a functional food, is limited by its low-water solubility, chemical instability, and poor bioavailability. The purpose of this work is to fabricate stable 7,8-DHF loaded zein/lactoferrin (LF) composite nanoparticles (zein/LF-DHF) to overcome these challenges. Results showed that mean particle size of zein/LF nanoparticles was about 74 nm with low polydispersity index (<0.200) and turbidity (<0.300) values. Zein/LF nanoparticles had good stability against pH (3.0–9.0), ionic strengths (0–500 mM NaCl at neutral pH) and long-term storage. Zein/LF nanoparticles showed spherical structures formed by hydrogen bonding and hydrophobic interactions, however, LF changed surface morphology of zein nanoparticles as observed by scanning electron microscope. X-ray diffraction indicated 7,8-DHF was presented in an amorphous state inside zein/LF nanoparticles. Most importantly, zein/LF-DHF had good redispersibility, and increased the encapsulation efficiency, chemical stability, water solubility and bioaccessibility of 7,8-DHF. Collectively, zein/LF nanoparticles are promising delivery systems for 7,8-DHF in functional foods.

Design of Caffeine-Loaded Nanostructured Lipid Carriers Containing Coconut Oil for Topical Application

Although caffeine was suggested as one of the pharmacological agents for the cellulite treatment, its skin permeation restricted. The present work was aimed at formulating caffeine loaded nanostructured lipid carriers (CAF-NLCs) containing coconut oil as a topical delivery system. CAF-NLCs were prepared by the ultrasonic emulsification method, using coconut oil as a liquid lipid. The proper selection of solid lipid and surfactants for these formulations were investigated. Subsequently, physicochemical properties, entrapment efficacy, stability, and in vitro drug release were evaluated. The CAF-NLCs containing coconut oil was successfully prepared using glyceryl behenate as a solid lipid and showed an interesting entrapment efficiency (62-99%). The obtained CAF-NLCs presented the nanosized range (≈ 60-390 nm), with a low polydispersity index and high negative zeta potential values (over ‐30 mV). However, the type and concentration of surfactant also affected these properties. These results suggested that CAF-NLCs containing coconut oil are the promising carrier for delivery of caffeine following topical application.