Polydispersity Index Values Research Articles

Biosynthesis of Silver Nanoparticles with Antifungal Potential

Abstract: Metallic nanoparticles, specifically silver nanoparticles, find huge applications in health, medicine, and drug delivery. However, the physical and chemical synthesis methods pose challenges regarding gener, action of toxic by-products, or high energy requirements. Hence biosynthetic approaches have gained interest in the last few years utilizing various sources including yeast, fungi, bacteria, or plant extracts containing reducing and capping agents like quercetin, apocyanin, gallic acid, alkaloids, tannins, etc. The present review would throw light on plant extracts containing such reducing and capping agents for the biosynthesis of silver nanoparticles, including the phytofactors and physicochemical parameters affecting the synthetic methods. Further characterization concerning the polydispersity index (ranging from 0-1) and zeta potential values (stable nanoparticles with ranges >+30 mV or <-30 mV) for improving stability would also be discussed. The potential and applications of silver based nanohybrids or nanocomposites will be described. The antibacterial potential of silver nanoparticles has been shown in previous reviews. Antifungal potential of biosynthetic silver nanoparticles obtained from plant extracts like Croton sparsiflorus morong leaf extract or aqueous extract of Phoenix dactylifera (date palm) pit evaluated on fungal strains will be illustrated in the present review. The underlying mechanism for the antifungal activity of silver nanoparticles will also be discussed. At the conclusion, the list of patents on biosynthetic silver nanoparticles and the limitations and regulatory guidelines for commercial production will be illustrated.

FORMULATION AND IN VITRO TESTS OF KETOPROFEN NANOSUSPENSION USING THE MILLING METHOD WITH POLYMER VARIATIONS

Objective: The aim of this research was to formulate ketoprofen nanosuspension with a variety of polymers and to compare the dissolution rate of the nanosuspensions with ketoprofen suspension. Methods: Ketoprofen nanosuspension was formulated by milling method using a different polymer such as Polyvinyl Pyrrolidone (PVP) K-30 (F1), Polyvinyl Alcohol (PVA) (F2) and Hydroxy Propyl Methyl Cellulose (HPMC) (F3). Nanosuspensions were prepared and characterized, including organoleptic, pH, particle size, zeta potential, Polydispersity Index (PI), specific gravity, crystalline state determination, physical stability at room temperature for 3 mo, and in vitro dissolution test compared with ketoprofen suspension. Results: The ketoprofen nanosuspensions with PVP K-30 and PVA showed stable preparations, while those with HPMC showed less stability, as indicated by sedimentation during storage. The particle size values of PVP K-30 and PVA were 10.004±0.03 nm; and 9.560±0.01 nm; zeta potential and polydispersity index values met the test requirements. The dissolution rate of the ketoprofen nanosuspensions was higher with a cumulative of F1, F2, and F3 were 83.35%; 85.00%, and 81.09% after 60 min, while the ketoprofen suspension was only 7.62%. Conclusion: The milling method of ketoprofen nanosuspensions with PVP and PVA has more stable physical characteristics than nanosuspension with HPMC. The ketoprofen nanosuspensions have a higher dissolution rate than the ketoprofen suspension.

Tailoring of magnetite nanocomposite of carboxymethyl chitosan impregnated with iron (III) oxide for enhanced degradation of reactive blue 19 dye and inactivation of harmful microbes in wastewater

The study investigates the fabrication of an innovative nanocomposite composed of carboxymethyl chitosan (CMCs) combined with different amounts of iron (III) oxide (Fe₂O₃) to boost dye degradation and antibacterial effectiveness. A top-down ball milling technique formed the nanocomposites and was extensively investigated for their structural, morphological, and functional features. The mean particle size of the 0.3Fe₂O₃/CMCs and 0.6Fe₂O₃/CMCs nanocomposites was 83.74 nm and 124.5 nm, respectively, with small polydispersity index (PdI) values suggesting satisfactory homogeneity. The adsorption effectiveness of Reactive Blue 19 (RB 19) dye was evaluated under different circumstances, with the 0.6Fe₂O₃/CMCs nanocomposite exhibiting the maximum adsorption capacity of 140 mg/g at an ideal pH of 5. Kinetic analyses indicated that the adsorption process adhered to a pseudo-second-order kinetic model. The nanocomposites had significant bactericidal performance, with the 0.6Fe₂O₃/CMCs nanocomposite exhibiting the most extensive inhibition zones, particularly against E. coli (28.4 mm) and Pseudomonas aeruginosa (23.2 mm). Furthermore, the reusability of the 0.6Fe₂O₃/CMCs nanocomposite was validated by five adsorption-desorption cycles, retaining over 90 % efficiency. The results underscore the efficacy of Fe₂O₃/CMCs nanocomposites as viable materials for wastewater treatment and antibacterial purposes, offering a promising approach for environmental remediation.

Development, Analysis, and Determination of Pharmacokinetic Properties of a Solid SMEDDS of Voriconazole for Enhanced Antifungal Therapy

Background: Voriconazole is an antifungal drug, which is classified under Bio-Classification System-II and has low water solubility (0.71 mg/mL) and high permeability. Hardly any endeavors have been made to increase the bioavailability of voriconazole. Objective: To develop and evaluate a solid SMEDDS (self-microemulsifying drug delivery system) for antifungal activity. Methods: Based on solubility studies of Labrafil-M 1994 CS (oil), Cremophor-RH 40 (a surfactant) and Transcutol-HP (a co-surfactant) were selected as components of the SMEDDS and a pseudo-ternary phase diagram was prepared. Thereafter, the oil, surfactant, and co-surfactant were mixed with altered weight ratios (1:1/1:2/2:1) and evaluated through various in vitro, in vivo analyses. Results: The particle size of the optimized formulation was observed to be 19.04 nm and the polydispersity index (PDI) value was found to be 0.162 with steady-state zeta potential. The optimized liquid SMEDDS was converted into a solid SMEDDS. Various adsorbents, such as Aerosil-200, Avicel-PH101, Neusilin-US2, and Neusilin UFL2 were screened to better detect the oil-absorbing capacity and flow properties of the powder. Neusilin UFL2 was selected as an adsorbent due to its better oil-absorbing capacity. DSC, X-ray diffraction, and dissolution studies were carried out to characterize the formulation. Further, the Pharmacokinetic profile was also studied in Wistar rats and the Cmax, tmax, and AUC0®t were calculated. The Cmax and AUC0®t plasma concentration is considerably better for the SMEDDS than for the pure drug and marketed formulation. Conclusions: This investigation clearly reveals the potential of developing a solid SMEDDS for candidiasis and invasive aspergillosis treatment, with better efficacy as compared to the commercially available marketed formulation.

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.

Ultrasonic Fabrication of Catechin Nanoemulsions from Green Tea with Enhanced Stability and Antioxidant Activity Optimized by Box-Behnken Design

Nanoemulsions are emulsions, either O/W (oil in water) or W/O (water in oil), with droplet diameters typically ranging from 50 to 1,000 nm. Research indicates that nanoemulsions are highly effective in enhancing the bioavailability, bioactivity, digestibility, stability, safety, quality and sensory attributes of food components. The study aimed to determine the optimum formulation and ultrasonic condition for fabricating catechin nanoemulsion (Ca-NE) from green tea with improved physical stability and antioxidant activity using response surface methodology. The effects of Medium Chain Triglyceride oil concentration (7.5 - 12.5 % w/w), Tween® 80 concentration (1 - 5 % w/w) and sonication time (5 - 15 min) on the droplet size, polydispersity index (PDI) and antioxidant activity presented by DPPH value of the Ca-NE were investigated using Box-Behnken design (BBD). The results found that droplet size and antioxidant activity of the Ca-NE were significantly (p < 0.05) affected by the proposed parameters, whereas the PDI value was slightly affected by those factors. The BBD results suggested that the Ca-NE fabrication condition was optimized with 7.5 % (w/w) oil concentration, 5 % (w/w) Tween® 80 concentration and a sonication time of 10.87 min. The optimum nanoemulsion showed good physical stability in terms of droplet size and PDI and had higher antioxidant activity than unencapsulated catechins when stored at 4 and 30 °C for 90 days. This study showed that catechin nanoemulsions fabricated by ultrasonication had good stability and antioxidant activity and, hence, had high potential for food and beverage applications in the food industry. HIGHLIGHTS The optimum nanoemulsion had good physical stability regarding droplet size and PDI when stored at 4 and 30 °C for 90 days. The ultrasonic fabrication of Ca-NE results in better retention of antioxidant activity than unencapsulated catechins. The ultrasonic fabrication provided the Ca-NE with good stability and high antioxidant activity. The results suggest that the obtained nanoemulsion of catechins has great potential in food or pharmaceutical applications. GRAPHICAL ABSTRACT

Unlocking the wound healing potential of Anastatica hierochuntica L. (Kaff Maryam) Extract's nanosuspension: UPLC-MS/MS metabolic profiling, formulation development and statistical optimization

BackgroundAnastatica hierochuntica L. (Kaff Maryam) is a desert plant with documented therapeutic applications. Various medicinal uses have been reported for the plant extract such as antioxidant, anti-inflammatory, antifungal, antimicrobial, hypoglycemic, hypolipidemic, and hepatoprotective activities. The abundant plants constituents are promising and encourage the investigation of novel therapeutic uses. The principal objective of this study was to identify the bioactive constituents of A. hierochuntica (AH) by phytochemical profiling of its ethanolic extract, alongside an investigation of its wound healing efficacy after being formulated into nanosuspension for topical localized wound treatment. MethodA comprehensive metabolomics study of the ethanolic extract of A. hierochuntica aerial parts was assessed using UPLC MS/MS technique. Additionally, the preparation of AH nanosuspension was executed utilizing the antisolvent-precipitation method. A D-optimal experimental design was adopted to investigate the influence of variables such as: stabilizer ratio, antisolvent: solvent ratio, and stabilizer type on particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The design also was employed in the optimization process. The selected optimal formula was further assessed for size characteristics, morphological identification by TEM, storage stability, FTIR, cytocompatibility with human skin fibroblast (HSF), and scratch assay on HSF to assess wound healing aptitude. ResultsChemical profiling of the aerial parts revealed an abundance of glucosinolates, flavonoids, flavolignans, and fatty acids. The optimized AH-nanosuspension showed small particle size (128.87 ± 26 nm), small PDI (0.136 ± 0.05), and high ZP absolute value (−37.53 ± 0.52 mV). Furthermore, TEM photography of the optimal nanosuspension formula exhibited circular non-aggregating nanosized particles. FTIR confirmed the successful formulation of the AH ethanolic extract into nanosuspension with no physicochemical interactions. Additionally, AH-nanosuspension demonstrated cytocompatibility with HSF with IC50 = 58.317 μg/mL. Moreover, both AH pure extract and AH-nanosuspension exhibited a remarkable cell migration rate and wound closure % which propounds an auspicious wound healing potential. ConclusionThe study accentuates the supremacy of the nanosized delivery approach of AH aerial parts ethanolic extract and warrants further in-vivo investigations to establish its clinical utility for wound management.

Enhancing Herbal Efficacy: Synthesis and Evaluation of Nanosuspension from Withania somnifera Root Extract

Background: Ayurveda emphasizes the balance of mind, body, and spirit, drawing on ancient texts that highlight the medicinal properties of herbs like Withania somnifera, known for its wide range of therapeutic applications and pharmacological benefits. Commonly referred to as Indian ginseng or Ashwagandha, Withania somnifera, demonstrates a variety of therapeutic effect , including anti-inflammatory, antitumor, sedative, hypnotic, deobstruent effects, narcotic, antioxidant, tonic, antistress, diuretic, aphrodisiac, immunomodulatory, and rejuvenating properties. Nanotechnology, particularly through the development of nanosuspensions, offers a significant advancement in medicine, addressing challenges like poor solubility and low bioavailability of lipophilic drugs. Nanosuspensions can enhance drug safety and efficacy by improving solubility and altering pharmacokinetics. Methods: This study focuses on formulating and characterizing a nanosuspension using an ethanolic extract of Withania somnifera roots. The nanosuspension (NSWS) underwent comprehensive characterization, utilizing techniques such as FT-IR spectroscopy, particle size analysis, zeta potential measurement, polydispersity index (PDI) assessment, Field emission scanning electron microscopy (FESEM), X-ray diffraction analysis, pH measurement, and stability testing. This study seeks to explore the potential of nanosuspensions, aiming to integrate nanotechnology with herbal medicine to improve the safety and efficacy of herbal formulations. Results: The nanosuspension (NSWS) shown particle size about 133.09 nm, and its uniform particle distribution was indicated by a Polydispersity Index (PDI) about 0.27. Stability and uniformity were further supported by the zeta potential, particle size, and PDI values. Conclusion: Nanosuspension formulations represents a versatile strategy to improve the therapeutic efficacy of hydrophobic drugs across various routes of administration. Keywords: Withania somnifera, Nanosuspension, Characterization, FT-IR, PDI, FESEM

Characterization and antibacterial application of peppermint essential oil nanoemulsions in broiler

In order to mitigate the risk of antibiotic resistance in poultry, scientists nowadays consider plant secondary metabolites to be a major organic antibacterial substitute. This study aimed to characterize and investigate the in silico, in vitro, and in vivo antibacterial effects of peppermint essential oil (PEO) in the form of a nanoemulsion (NE), termed PEONE. Menthol as a major compound of PEO has been identified by gas chromatography and mass spectroscopy (GCMS) analysis as 32.3 %, while lower droplet size, polydispersity Index (PDI), and optimum zeta potential values depicted the stability of PEONE have been observed and validated by transmission electron microscopy (TEM) micrograph image. In silico antibacterial activity was studied by molecular docking of menthol and enrofloxacin with Topoisomerase IV protein (PDB: 1s16;) of Escherichia coli K12 MG1655 and this effect was validated by in vitro and in vivo analysis. In vitro analysis, sustained release of PEONE has been observed against Escherichia coli and Staphylococcus aureus. In this study for in vivo experiments (n = 90) day-old broiler chicks were distributed into 6 dietary treatments with 5 replicates of 3 birds per replication. Dietary treatments included 1) Negative control (basal diet), 2) Positive control (basal diet + 200 µl enrofloxacin), 3) 25 µl PEONE + basal diet, 4) 50 µl PEONE + basal diet, 5) 75 µl PEONE + basal diet, and 6) 100 µl PEONE + basal diet. Analyzed data by different statistical tools confirmed that PEONE significantly affected body weight gain (BWG) with an improved feed conversion ratio (FCR) compared to the control group. A significant increase in cecal Lactobacillus count and a decrease in total coliform was observed. Positive effects on physiological parameters, visceral organs, and meat quality characteristics have been observed. In conclusion, our experiments suggest that PEONE can be used in the broiler industry as a substitute for antibiotics to minimize bacterial resistance.

Preparation and evaluation the effects of retinoic acid loaded proliposomal nanofibers on microbial biofilm inhibition

The electrospinning method involves the production of different drug delivery systems using various polymers. The production of proliposomes with electrospinning provides the hybridization of two novel drug delivery systems. Retinoic acid, also known as all-trans retinoic acid (ATRA), is a common and effective drug for acne therapy. This study aimed to prepare ATRA-loaded proliposomal nanofibers and evaluate their effectiveness on microbial biofilm inhibition. Blank and ATRA-loaded proliposomal nanofiber formulations were fabricated in various polyvinylpyrrolidone, phosphatidylcholine and cholesterol ratios. TEM images verified the rapid formation of the liposomes after the hydration of nanofibers. The vesicle size, polydispersity index and zeta potential values of self-assembled liposomes were measured. The vesicle size values were found to be 321.9–363.8 nm with PDI values varying between 0.332 and 0.511 and zeta potential values of (−16.8) to (−20.5)mV. ATRA-loaded proliposomal nanofibers provided higher bioadhesion (0.25 mJ/cm2) than the commercial cream (0.07 mJ/cm2). The short-term stability results showed that the initial characteristics remained for three months at 4 °C. The proposed ATRA-loaded self-assembled proliposomal system provided antibacterial, fungistatic or fungicidal effects superior to retinoic acid itself and inhibited biofilm formation in lower concentrations. This approach can combine the stability advantage of nanofibers in the dry state with the high effectiveness of liposomes in acne treatment presenting antibacterial and anti-biofilm-forming activity against Candida albicans and Cutibacterium acnes.

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).

Clarithromycin-tailored cubosome: A sustained release oral nano platform for evaluating antibacterial, anti-biofilm, anti-inflammatory, anti-liver cancer, biocompatibility, ex-vivo and in-vivo studies

The clinical implication of clarithromycin (CLT) is compromised owing to its poor solubility and, subsequently, bioavailability, unpalatable taste, rapid metabolism, short half-life, frequent dosing, and adverse effects. The present investigation provides an innovative sustained-release oral drug delivery strategy that tackles these challenges. Accordingly, CLT was loaded into a cubosome, a vesicular system with a bicontinuous cubic structure that promotes solubility and bioavailability, provides a sustained release system combating short half-life and adverse effects, masks unpleasant taste, and protects the drug from destruction in gastrointestinal tract (GIT). Nine various formulas were fabricated using the emulsification method. The resulting vesicles increased the encapsulation efficiency (EE %) from 57.64 ± 0.04 % to 96.80 ± 1.50 %, the particle size (PS) from 147.30 ± 21.77 nm to 216.61 ± 5.37 nm, and the polydispersity index (PDI) values ranged from 0.117 ± 0.024 to 0.278 ± 0.073. The zeta potential (ZP) changed from −20.65 ± 2.01 mV to −33.98 ± 2.60 mV. Further, the release profile exhibited a dual release pattern within 24 h., with the percentage of cumulative release (CR %) expanding from 30.06 ± 0.42 % to 98.49 ± 2.88 %, optimized formula was found to be CC9 with EE % = 96.80 ± 1.50 %, PS = 216.61 ± 5.37 nm, ZP = −33.98 ± 2.60 mV, PDI = 0.117 ± 0.024, CR % = 98.49 ± 2.88 % and IC50 of 0.74 ± 0.19 µg/mL against HepG-2 cells with scattered unilamellar cubic non-agglomerated vesicles. Additionally, it exhibited higher anti-MRSA biofilm, relative bioavailability (2.8 fold), and anti-inflammatory and antimicrobial capacity against Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, and Staphylococcus aureus compared to free CLT. Our data demonstrate that cubosome is a powerful nanocarrier for oral delivery of CLT, boosting its biological impacts and pharmacokinetic profile.

Antimicrobial activity of Zn-nanoparticles synthesized by leaf extract of Capparis spinosa

In the last 2 decades, nanotechnology has developed significantly. It is now easy to perform materials reduction to a nano size called nanoparticles (NPs). One significant development is the use of plant extracts containing phytochemical compounds as reducing agent. Capparis spinosa, a shrub plant, was used in the synthesis of zinc oxide and iron oxide NPs. Synthesis and characterization of ZnONPs by consumed phytochemical compounds of C.spinosa leaf extract was performed. Synthesize ZnONPs from the aqueous leaf extract and characterize them using FT-IR, DLS and STEM and investigate the antimicrobial activity of NPs using agar well diffusion and the minimum inhibitory concentration (MIC). The aqueous leaf extract of C.spinosa contain flavonoids, alkaloids, tannin, phenol and saponin. FT-IR analysis showed peaks in C spinosa extract and ZnONPs spectra where different functional groups with unique peaks for ZnONPs were detected indicating the formation of specific bonds. DLS spectroscopy revealed polydispersity index (PDI) values of 0.638 for ZnONPs and STEM images for ZnONPs showed irregular NPs with sizes ranging from 33.75 to 89.14 nm. Antimicrobial test by agar well diffusion showed an inhibition zone of ZnONPs against all test microbial genera except C. glabrata and higher effect was against P.vulgaris with diameter of inhibition zone equal to 15.5± 0.7 mm. The MIC values of ZnONPs against P.vulgaris and C.Kruesi were the same (0.25mg/ml) while S.aureus, S.pyogens and C.glabrata showed less MIC value (0.125mg/ml). In conclusion, green synthesized ZnONPs showed an antimicrobial effect on skin associated microbial which can be adopted and developed with the aim of using it as an alternative to completely chemically synthesized antibiotics.

Comparison of free vs. liposomal naringenin in white adipose tissue browning in C57BL/6j mice

Naringenin may play a role in browning by increasing thermogenic gene expression. In this study, we encapsulated naringenin using a liposomal formulation and examined the effects of both free and liposomal naringenin on white adipose tissue browning in C57BL6/J mice. In the first phase of the study, naringenin was encapsulated by the liposome method, which is biocompatible and biodegradable. The physical and chemical properties of liposomal naringenin were tested. In the second phase, a total of 48 six-week-old mice were divided into two main groups: prevention and recovery. Each main group was divided into four subgroups: nano-naringenin, void, free-naringenin, and control. The prevention group received a high-fat diet for 10 weeks along with weekly intravenous injections of 20 µM naringenin. On the other hand, the recovery group was first subjected to a high-fat diet for 10 weeks, followed by an additional 10 weeks of the same diet, along with weekly intravenous injections of 20 µM naringenin. Body weight was measured once per week, and brown adipose tissue, inguinal white adipose tissue, and serum samples were collected from each mouse. The mean particle size, polydispersity index and zeta potential values of liposomal naringenin were ∼207 nm, 0.35, and −27 mV, respectively. The encapsulation and loading efficiencies of liposomal naringenin were 94.6 and 19.2%, respectively. Liposomal naringenin exhibited sustained-release behavior, while free naringenin showed a burst-release profile. Liposomal naringenin showed the best physical stability in light and at 4 °C, while free naringenin was more chemically stable in light and at 4 and 22 °C. Free and liposomal naringenin did not significantly reduce weight gain. In the prevention group, liposomal naringenin increased PRDM16 gene expression in inguinal white adipose tissue 4.29 times more than free naringenin (p = 0.010). However, neither formulation significantly altered the expression levels of other browning or adipogenesis markers in the tissues. The results suggest that free naringenin can be efficiently encapsulated in biocompatible and biodegradable nanoparticles. Further research is needed to better understand the physiological effects of liposomal naringenin.

Ethanolic Cashew Leaf Extract Encapsulated in Tripolyphosphate–Chitosan Complexes: Characterization, Antimicrobial, and Antioxidant Activities

Ethanolic cashew leaf extract (ECL-E) is rich in phenolic compounds and shows remarkable antioxidative and antimicrobial activities. Encapsulation could stabilize ECL-E as the core. Tripolyphosphate (TPP)–chitosan (CS) nanoparticles were used to load ECL-E, and the resulting nanoparticles were characterized. The nanoparticles loaded with ECL-E at different levels showed differences in encapsulation efficiency (47.62–89.47%), mean particle diameters (47.30–314.60 nm), positive zeta potentials (40.37–44.24 mV), and polydispersity index values (0.20–0.56). According to scanning electron micrographs, the nanoparticles had a spherical or ellipsoidal shape, and a slight agglomeration was observed. The appropriate ratio of CS/ECL-E was 1:3, in which an EE of 89.47%, a particle size of 256.05 ± 7.70 nm, a zeta potential of 40.37 ± 0.66 mV, and a PDI of 0.22 ± 0.05 were obtained. The nanoparticles also exhibited high antioxidant activities, as assayed by DPPH and ABTS radical scavenging activities, ferric reducing ability power (FRAP), and oxygen radical absorbance capacity (ORAC). Low minimum inhibitory concentration and minimum bactericidal concentration were observed against Pseudomonas aeruginosa (9.38, 75.00 mg/mL) and Shewanella putrefaciens (4.69, 75.00 mg/mL). In addition, ECL-E loaded in nanoparticles could maintain its bioactivities under various light intensities (1000–4000 Lux) for 48 h. Some interactions among TPP, CS, and ECL-E took place, as confirmed by FTIR analysis. These nanoparticles had the increased storage stability and could be used for inactivating spoilage bacteria and retarding lipid oxidation in foods.

Curcumin-cyclodextrin inclusion complexes embedded in intrinsically active nano-assemblies: Preparation, characterization, antibacterial and antibiofilm activity against ESKAPE pathogens

Curcumin loaded β-CD inclusion complexes (CCDs) embedded in intrinsically active rhamnosomes (CCDRs) were developed as alternative antimicrobials at the nano-scale to control ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. The physicochemical analysis of CCDRs demonstrated that the addition of glycolipids (rhamnolipids) during the development of liposomes (phospholipids based) provided stability while the average size (158±5 nm) and polydispersity index (PDI) values of 0.2 demonstrated homogenous population of rhamnosomes. The incorporation of rhamnolipids with phospholipids increased the zeta potential to -45±1 mV with 76±1 % encapsulation efficiency for curcumin with enhanced photochemical and storage stability. In vitro, release studies demonstrated sustained release of curcumin due to its incorporation in β-CD molecular buckets, which were loaded in the aqueous liposomal core. These CCDRs with intrinsic antibacterial and antibiofilm potential enhanced the antimicrobial spectrum against ESKAPE pathogens demonstrating synergism between curcumin and rhamnolipids, by targeting multiple sites of bacterial cells and biofilms as compared to conventional antibiotics. Our study outlines that rhamnolipids and curcumin loaded inclusion complexes together offer an exciting potential for functionalized liposomal delivery systems that would be promising for the development of effective alternative therapeutics against ESKAPE pathogens.

Modified release, enriched biocompatibility, and enhanced oral bioavailability as precious features of nitrofurantoin-loaded polymeric nanoparticles

Nitrofurantoin (NTF) is a first-line therapy for treating urinary tract infections. However, gastric upset, short half-life, and poor bioavailability of NTF are major challenges for clinical use. Hence, the current work incorporated NTF in polymeric nanoparticles (NPs).NTF-loaded NPs (NTF-NPs) were prepared using Eudragit RS100 (RS100), DL-lactide/glycolide copolymer (PLGA), and their mixture at a ratio of 1:1 w/w (RS100/PLGA) as polymers. Pluronic F68, Tween 80, and polyvinyl alcohol (PVA) were applied as stabilizers. The particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency were determined. Three optimized formulations of NPs; F3, F13, and F29 were selected for further coating with Eudragit L100 (L100) and Eudragit S100 (S100). The optimized NPs and the corresponding coated ones were evaluated for solid-state characterization, morphology, and in vitro release. L100-coated F13 (LCF13) was further investigated for biocompatibility with normal oral epithelial cell (OEC) and Vero cell lines. A pharmacokinetic study using a rat model was also conducted.The results revealed that Tween 80 and PVA-stabilized NPs accomplished a nano-sized range with polymer- and stabilizer-dependent PDI and ZP. Optimized formulations: F3, F13, and F29 were selected for further coating where PS and PDI values not exceeding 260 nm and 0.502, respectively. The coated NPs had negative ZP ranging from −11.00 ± 2.70 to −40.20 ± 1.40 mV, attributable to the L100 or S100 coating. The solid-state characterization confirmed a transition of NTF to amorphousness. The spherical shape with the distinctive halo-like appearance of the coated NPs was proved. Additionally, the coating warranted a prolonged release of NTF especially for LCF13 avoiding the burst effect. Allowing enriched biocompatibility, LCF13 showed an IC50 value of 224.00 ± 9.20 μM for the OEC cell line, whereas a greater IC50 exceeding 300 μM was recognized for the LCF13-treated Vero cell line. After a single oral dose, LCF13 could provide a discernible increase in the extent of absorption (Du∞ = 863.31 ± 73.71 μg) with a significant extension of the absorption rate (tmax and t1/2 of 3 and 2.51 ± 0.317 h, respectively).LCF13 could be considered a controlled and safe nanocarrier that delivered significantly higher levels of NTF for a longer duration than NTF dispersion.

An in vitro study for reducing the cytotoxicity and dose dumping risk of remdesivir via entrapment in nanostructured lipid carriers

The aim of this study was to synthesize and evaluate nanostructured lipid carriers (NLCs) loaded with Remdesivir (RDV) to control its side effects in COVID-19 patients. Due to the low solubility and short half-life of RDV in the blood, an injectable formulation was prepared using sulphobutylether-beta-cyclodextrin. However, it can accumulate in the kidney and cause renal impairment. NLCs improve the parenteral delivery of hydrophobic drugs such as RDV by increasing drug solubility and bioavailability. For the synthesis of RDV-NLCs, the aqueous phase containing Tween 80 was injected into the lipid phase under rapid stirring and was sonicated. The experimental conditions were optimized using Box-Behnken design and Design Expert software. The optimum formulation contained a total lipid of 2.13%, a total surfactant of 1%, and a hot bath time of 71 min. The optimum formulation showed particle size, polydispersity index, zeta potential, and entrapment efficiency values of 151.0 ± 1.7 nm (from 149.1 to 152.1), 0.4 ± 0.1 (from 0.3 to 0.5), −43.8 ± 1.2 mV (from −42.4 to −44.7), and 81.34 ± 1.57% (from 79.52 to 82.33%), respectively. RDV-NLCs showed acceptable stability for 30 days at 25 ℃ and were compatible with commonly used intravenous infusion fluids for 48 h. FE-SEM images of RDV-NLC showed spherical particles with a mean diameter of 207 nm. The NLC-RDV formulation showed a sustained release of RDV with a low risk of dose-dumping, minimizing potential side effects. In addition, RDV in the form of RDV-NLC causes less cytotoxicity to healthy normal kidney cells, which is expected to reduce renal impairment in COVID-19 patients.

Design and optimization of DPC-crosslinked HPβCD nanosponges for entrectinib oral delivery: formulation, characterization, and pharmacokinetic studies

BackgroundIn advanced or metastatic cancers characterized by specific genetic alterations, heightened growth and resistance to conventional therapies are common. Targeted treatments like entrectinib (ENT) precisely inhibit aberrant signaling pathways, potentially enhancing outcomes. The objective of this research is to develop and enhance the effectiveness of entrectinib-loaded nanosponge formulations by utilizing hydroxypropyl-β-cyclodextrin (HPβCD) to improve its oral bioavailability.ResultsThe study employed surface response methodology and Design-Expert® software to optimize key formulation variables such as the molar concentration ratio of the polymer and cross-linker, as well as process variables such as stirring speed and duration. Optimization focused on particle size, polydispersity index, and percentage entrapment efficiency. Validation methods encompassed Fourier transform spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), in vitro release studies, and in vivo studies.After optimization, ENT-loaded HPβCD NSPs were formulated with a molar ratio (P:CL) of 0.800 mg, stirred at 3000 rpm for 420 min, achieving a desirability of 0.926. Predicted values for PS (particle size), PdI (polydispersity index), and EE % (entrapment efficiency) were 146.98 nm, 0.263, and 88.29%, respectively. The optimized formulation showed a mean size of 151.8 ± 5.6 nm, PDI of 0.233 ± 0.049, and EE of 87.36 ± 1.61%. Further validation through various analyses confirmed the optimization's efficacy, with notable improvements demonstrated in AUC0-t (6.30-fold) and Cmax (4.10 times) compared to the free drug.ConclusionThe findings of the study indicated that nanosponges exhibit promise as an effective carrier for delivering entrectinib, addressing for advance tumor effectively by enhancing release and bioavailability in the treatment of cancer.

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.