Molar Ratio Of Cholesterol Research Articles

Improved Topical Antifungal Medication using Sertaconazole Bilosomes: In vitro Permeability, Cytotoxicity, and Clinical Assessment

Objective: The purpose of the current study was to develop Sertaconazole bilosomes (SBs) with enhanced permeability, skin deposition, anti-fungal properties, and clinical efficacy. Methods: By changing span 60 to cholesterol molar ratio, bile salt type, and concentration, 12 formulations of SBs were prepared using the thin film hydration method and characterized by particle size (PS), zeta potential (ZP), polydispersity index (PDI), % entrapment efficiency (% EE), and % cumulative drug released after 8h (% Q8h ) and 24h (% Q24h). The optimized formulation (SB 5) was incorporated into 1% Carbopol 940 hydrogel (SBG 5) and tested for ex-vivo permeability, skin deposition, and anti-fungal efficacy compared to the commercial formulation (Dermofix® cream) and sertaconazole alone hydrogel (SAG). A randomized controlled clinical trial of SBG 5 compared to Dermofix® cream and SAG was done on 30 patients diagnosed with Tinea corporis with a 4-week follow-up. Results: SB 5 showed PS of 158 ± 6.4nm, ZP of −55 ± 1.7mV, PDI of 0.16 ± 0.01, % EE of 96 ± 3.4, % Q8h of 70.3 ± 3.6, and % Q24h of 97.2 ± 3.0. SBG 5 exhibited in vitro release after 24h (1.25 and 1.51-fold), skin permeability (1.6 and 2.3-fold), skin deposition (3.86 and 14.82-fold), and anti-fungal efficacy against Candida albicans (two and 1.44-fold) compared to Dermofix® cream and SAG respectively. Patients receiving SBG 5 exhibited a 1.25 and 1.8-fold higher recovery rate on days 14 and 21 respectively compared to Dermofix® cream, and a 4.5 and two-fold recovery rate on days 14 and 21 respectively compared to SAG. Conclusion: Bilosomes could be utilized to enhance permeability, skin deposition, anti-fungal properties, and clinical efficacy of Sertaconazole.

Bioresponsive gingerol-loaded alginate-coated niosomal nanoparticles for targeting intracellular bacteria and cancer cells

Targeting and treating intracellular pathogen infections has been long-standing challenge, particularly in light of the escalating prevalence of antimicrobial resistance. Herein, an optimum formulation of alginate (AL)-coated niosome-based carriers for delivery of herbal extract Gingerol (Gin) was developed to treat intracellular pathogen infections and cancer cells. We used Gin-Nio@AL as a model drug to assess its efficacy against Gram-negative/positive bacteria and breast cancer cell lines. Our investigation affirmed its heightened antibacterial and anticancer properties. The antibacterial activity of Gin-Nio@AL against intracellular Staphylococcus aureus (S. aureus) and pseudomonas aeruginosa (P. aeruginosa) was also tested. In the current study, the niosome nanoparticles containing herbal extract Gingerol were optimized regarding lipid content and Surfactant per Cholesterol molar ratio. The developed formulation provided potential advantages, such as smooth globular surface morphology, small diameter (240.68 nm), pH-sensitive sustained release, and high entrapment efficiency (94.85 %). The release rate of Gin from AL-coated niosomes (Gin-Nio@AL) in physiological and acidic pH is lower than uncoated nanoparticles (Gin-Nio). Besides, the release rate of Gin from niosomal formulations increased in acidic pH. The Gin-Nio@AL demonstrated good antimicrobial activity against S. aureus and P. aeruginosa, and compared to Gin-Nio, the MIC values decreased to 7.82 ± 0.00 and 1.95 ± 0.00 μg/mL, respectively. In addition, the time-kill assay results showed that the developed formulation significantly reduced the number of bacteria in both strains compared to other tested groups. The microtiter data and scanning electron microscope micrography showed that Gin-Nio@AL has a more significant inhibitory effect on biofilm formation than Gin-Nio and Gin.The cell cytotoxicity evaluation showed that Gin-Nio@AL reduced the survival rate of MDA-MB-231 cancer cells to 52.4 % and 45.2 % after 48 h and 72 h, respectively. The elimination of intracellular pathogens was investigated through a breast cancer cell infection in an in vitro model. Gin-Nio@AL exhibited an enhanced and sustained intracellular antibacterial activity against pathogens-infected breast cancer cells compared to other tested formulations. Overall, Gin-Nio@AL enables the triggered release and targeting of intra-extra cellular bacteria and cancer cells and provides a novel and promising candidate for treating intracellular pathogen infections and cancer cells.

Preparation, characterization, and Co-delivery of cisplatin and doxorubicin-loaded liposomes to enhance anticancer Activities

Ovarian cancer stands as a leading cause of cancer-related deaths among women globally. This malignancy has hindered successful treatment attempts due to its inherent resistance to chemotherapy agents. The utilization of cisplatin and doxorubicin-loaded liposomes emerges as a strategically advantageous approach in the realm of biomedical applications. This strategy holds promise for augmenting drug efficacy, mitigating toxicity, refining pharmacokinetics, and facilitating versatile drug delivery while accommodating combination therapies. In pursuit of scholarly investigations, the eminent databases, including PubMed/MEDLINE, ScienceDirect, Scopus, and Google Scholar, were meticulously scrutinized. Within this study, a nano-liposomal formulation was meticulously designed to serve as a co-delivery system. This system was optimized by varying lipid concentrations, hydration time, and DSPC: cholesterol molar ratios to efficiently encapsulate and load doxorubicin (DOX) and cisplatin (CIS) to overcome drug resistance problems. The Lipo (CIS + DOX) formulation underwent rigorous characterization including dimensions, entrapment efficiencies and drug release kinetics. Notably, the entrapment efficiency of cisplatin and doxorubicin loaded liposomal nanoparticles was an impressive 85.29 ± 1.45 % and 73.62 ± 1.70 %, respectively. Furthermore, Lipo (CIS + DOX) drug release kinetics exhibited pH-dependent properties, with lower drug release rates at physiological pH (7.4) than acidic (pH 5.4). Subsequent cytotoxicity assays revealed the enhanced biocompatibility of dual-drug liposomes with HFF cells compared to free drug combinations. Impressively, CIS and DOX-loaded liposomes induced significant cytotoxicity against A2780 in comparison to free drugs and combinatorial free drugs. Furthermore, the CIS and DOX-loaded liposome showed induced apoptotic potential and cell cycle arrest in A2780 compared to CIS, DOX, and their combination (CIS + DOX). Combining CIS and DOX via liposomal nanoparticles introduces a promising therapeutic avenue for addressing ovarian cancer. These nano-scale carriers hold the potential for attenuating the untoward effects of singular drugs and their attendant toxicities.

Design and Evaluation of Liposomal Sulforaphane-Loaded Polyvinyl Alcohol/Polyethylene Glycol (PVA/PEG) Hydrogels as a Novel Drug Delivery System for Wound Healing.

Hydrogel scaffold has been widely applied as drug delivery systems for treating skin injuries. However, the poor drug loading and rapid drug release of hydrogel restricted their application. In the current study, we present a nanoliposome containing sulforaphane (SF) as a nano-drug delivery system that is encapsulated within the scaffold hydrogel system to overcome these limitations and improve wound healing. The hydrogel substrate consisting of 10% polyvinyl alcohol (PVA)/5% polyethylene glycol 400 (PEG400) was prepared by the freeze-thaw method, and the nanoliposomal system was manufactured by the thin film hydration method at different molar ratios of cholesterol: SPC: DPPC: DSPE-PEG2000. The nanoliposome and hydrogel system was characterized by physicochemical analyses. The findings achieved from the optimization of the sulforaphane-loaded nanoliposome (SFNL) displayed an increase in the molar ratio of SPC, leading to a higher entrapment efficiency and a gradual release profile. Narrow size distribution, optimal electrical charge, and the lack of molecular interactions between SF and nanoliposome components in the FTIR analysis make SFNL a suitable drug delivery system for the wound healing process. The obtained SFNL-encapsulated freeze-thawed hydrogel system has sufficient and specific swelling ability at different pH values and increased mechanical strength and elongation. Additionally, the release pattern of SFNL at different pH values showed that the release of SF from liposomes depends on the pH value of the environment and accelerates in line with decreasing pH values. Encapsulation of nanoliposomal SF in the hydrogel structure provides a sustained release pattern of SF compared to its free form and increased as the pH environments continued to raise. The cytotoxicity and cell uptake of SFNL-loaded hydrogels against human skin fibroblasts (HFF cell line) were investigated. The in vitro analyses displayed that the toxicity properties of SF and SFNL were dose-dependent, and SFNL exhibited lower toxicity compared to free SF. Furthermore, the proper cell compatibility of the prepared hydrogel against the HFF cell line was confirmed by the MTT assay. These findings imply that the hydrogel scaffold loaded with SFNL may have wound-healing potential.

Formulation of a gambier catechin-loaded nanophytosome and the MTT assay on HeLa cell lines

Background: Catechins are good free radical scavengers but exhibit low stability and permeability. Nanophytosomes are currently being developed as the delivery system for phytoconstituents to protect them from decomposition by oxidants or enzymes and increase their permeability. Objectives: To formulate gambier catechin-loaded nanophytosomes and perform the MTT assay on HeLa cell lines. Method:Five formulations were prepared using soya lecithin at various molar ratios of cholesterol by thin-layer hydration and sonication. The nanophytosomes were characterised by the determination of vesicle size, zeta potential, polydispersity index, morphology with Transmission Electron Microscope, Fourier Transform Infrared Spectroscopy (FT-IR) analysis, freeze and thaw test, entrapment efficiency, and the in vitro cytotoxicity test. Result: The optimal formula (F4) with a molar ratio of 1:1:0.8 (catechin:lecithin:cholesterol) resulted in spherical vesicles with an average size (106 ± 0.218) nm, zeta potential -68 mV, polydispersity index 0.412, 93.5% entrapment efficiency and that were stable to temperature changes. FT-IR showed the formation of catechins and lecithin complexes. The activity of catechin-loaded nanophytosomes against HeLa cells showed an IC50 of 36.307 g/ml. There was a significant difference in the average percentage of cells undergoing apoptosis in all treatment groups (p < 0.05). Conclusion: Catechin-loaded nanophytosomes with a molar ratio of 1:1:0.8 (catechin:lecithin:cholesterol) showed moderate cytotoxic activity against HeLa cell lines.

Preparation of Artemisia Turcomanic Encapsulated Niosomal Nanocarriers and Evaluation of Anticancer Activities and Apoptosis Gene Expression Analysis in HeLa Cells.

Artemisia turcomanic as a natural antibacterial agent, exhibited significant antibacterial effect in the treatment against cancer. This study is the first to investigate size, encapsulation efficiencies, release behavior of Artemisia turcomanic loaded niosomal nanocarriers , and the anticancer effect of niosomal nanocarriers by MTT assay, flow cytometry, and real time (on Hela cell lines). When the molar ratio of cholesterol: surfactant was 1:2 and the liquid content was 300 µmol, the highest percentage of entrapment efficiency was 83.25%. Moreover, niosomal formulation showed a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 5.4). In addition, The apoptotic rate of Artemisia loaded niosomes on Hela cell lines was higher than free extract and pristine niosome. Also, reduction in the expression levels of Bcl2, caspase-3, and p53 genes and increase in the expression level of BAX after treatment with Artemisia turcomanic-loaded niosomes were more significant than those after treatment with free Artemisia turcomanic and blank niosome. The cytotoxicity results of samples presented that Artemisia turcomanic loaded niosomes are more beneficial in the death of Hela cell lines.

Understanding the Effects of Cholesterol and Ethanol on the Stability and Morphology of Bicellar Mixtures

Elucidating the stability and morphology of bicellar mixtures is of great importance in the biomedical field. In this report, self-assembly cholesterol (CHOL)-containing bicellar mixtures were investigated, that were composed of long chain hydrogenated soybean phospholipids (HSPC), short chain 1, 2-diheptanoyl-sn-glycero-3-phosphocholine (DHPC) phospholipids, negatively charged dipalmitoyl phosphatidylglycerol (1, 2-dipalmitoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DPPG), and polyethylene glycol conjugated (1, 2-dimyristoyl-sn-glycero-3-phosphoethano-lamine-N-[methoxy (polyethylene glycol)-2000] (PEG2000-DSPE) lipid. Analytical techniques like; Dynamic Light Scattering (DLS), Small Angle X-Ray Scattering (SAXS), and Transmission Electron Microscopy (TEM) were used to investigate the stability and morphology changes of these bicellar mixtures. The effects of CHOL and ethanol on the morphology and stability of these bicellar mixtures under 50ºC were also studied. The transition happened from nanodiscs to nanovesicles when the CHOL molar ratio was 40% in pure water. However, adding ethanol could improve CHOL solubility when the ethanol weight ratio was 20 wt% (ethanol/lipid) that favored nanodiscs-nanovesicle transition. Additionally, the ammonium sulfate maybe another factor that could affect the morphology of these bicellar mixtures form high order d-spacing structure.

Cholesterol concentration effect on bilayer membranes and its role in designing efficient liposomal drug delivery systems.

Liposomal drug delivery systems provide a versatile therapeutic platform for treating numerous diseases. Cholesterol, as a common component of many liposomal drug delivery systems, plays a crucial role in enhancing mechanical strength and decreasing the permeability of biomembranes. However, the ratio required for a proper formulation is poorly recognized. In this study, all-atom molecular dynamics simulations are performed to characterize the effect of cholesterol concentration in bilayers. To prepare liposomes, we simulate DSPC (1,2-distearoyl-sn-glycero-3-phosphocholine) phospholipid combined with different molar ratios of cholesterol (100, 80-20, 70-30, and 60-40%) in both planar and spherical bilayers. Furthermore, it has been quantified how a range of bilayer properties, including area per lipid, leaflet interdigitation, membrane thickness, and lipid Scd order parameters, are altered by variation in concentrations of lipid and cholesterol. Therefore, the most suitable amount of cholesterol and lipid to prepare stable and controlled drug release vehicles is obtained by screening the lipid and cholesterol ratio arrangement. Compared to membranes without cholesterol, the influence of cholesterol on lipid bilayers is revealed. These results provide a better understanding of the fundamental characteristics of the structure and dynamics of cholesterol-containing membranes. By revealing molecular details of interactions between cholesterol and phospholipids, these simulations accurately represent atomic-level characteristics of the planar and spherical bilayers. The simulations presented here shed light on the workings and limitations of liposomal drug delivery technology and establish a computational framework for the rational design of liposomes in drug delivery systems.

Concentration-Dependent Effects of Cholesterol on the Dimerization of Amyloid-β Peptides in Lipid Bilayers.

Membrane disruption mediated by the accumulation of amyloid-β (Aβ) on cell membranes is central to the pathogenesis of Alzheimer's disease (AD). Cholesterol, an important component of membranes, is well-recognized as a risk factor in AD. It can affect the aggregation and pore formation of Aβ on membranes whereas the specific effects are rather complex, particularly regarding the non-linear response to cholesterol concentrations. Yet, the mechanistic understanding of the role of cholesterol in Aβ-membrane interactions remains incomplete. Herein, we employed microsecond-scale molecular dynamics simulations to investigate the effects of cholesterol on Aβ dimerization in a lipid bilayer containing different molar ratios of cholesterol (0, 20, and 40 mol %). Cholesterol reduces the time required for the formation of stable dimers and exerts dual effects on Aβ-membrane interactions. First, cholesterol promotes the extraction of the C-terminal region from the membrane to water. Consequently, at the ratios of 0 and 20 mol %, peptides are anchored at the membrane-water interface, but they are repelled to water at a ratio of 40 mol % with high structural flexibility. Second, cholesterol weakens Aβ-membrane interactions, thereby enhancing inter-peptide interactions. The former is favorable for dimerization while the latter is not. The balance between two factors eventually leads to a non-monotonic effect on the degree of dimerization, whereby the number of inter-peptide contacts is the largest at a cholesterol ratio of 20 mol %. These results provide atomistic insights into the regulation mechanism of Aβ42 aggregation by cholesterol and help to understand the pathological link between cholesterol and AD.

Optimized Apamin-Mediated Nano-Lipidic Carrier Potentially Enhances the Cytotoxicity of Ellagic Acid against Human Breast Cancer Cells.

Ellagic acid has recently attracted increasing attention regarding its role in the prevention and treatment of cancer. Surface functionalized nanocarriers have been recently studied for enhancing cancer cells’ penetration and achieving better tumor-targeted delivery of active ingredients. Therefore, the present work aimed at investigating the potential of APA-functionalized emulsomes (EGA-EML-APA) for enhancing cytototoxic activity of EGA against human breast cancer cells. Phospholipon® 90 G: cholesterol molar ratio (PC: CH; X1, mole/mole), Phospholipon® 90 G: Tristearin weight ratio (PC: TS; X2, w/w) and apamin molar concentration (APA conc.; X3, mM) were considered as independent variables, while vesicle size (VS, Y1, nm) and zeta potential (ZP, Y2, mV) were studied as responses. The optimized formulation with minimized vs. and maximized absolute ZP was predicted successfully utilizing a numerical technique. EGA-EML-APA exhibited a significant cytotoxic effect with an IC50 value of 5.472 ± 0.21 µg/mL compared to the obtained value from the free drug 9.09 ± 0.34 µg/mL. Cell cycle profile showed that the optimized formulation arrested MCF-7 cells at G2/M and S phases. In addition, it showed a significant apoptotic activity against MCF-7 cells by upregulating the expression of p53, bax and casp3 and downregulating bcl2. Furthermore, NF-κB activity was abolished while the expression of TNfα was increased confirming the significant apoptotic effect of EGA-EML-APA. In conclusion, apamin-functionalized emulsomes have been successfully proposed as a potential anti-breast cancer formulation.

Surface-tailoring of emulsomes for boosting brain delivery of vinpocetine via intranasal route: in vitro optimization and in vivo pharmacokinetic assessment

Vinpocetine (VNP), a semisynthetic active pharmaceutical ingredient, is used for oral management of cerebrovascular diseases because of its ability to enhance the blood flow to the brain. However, despite that, the therapeutic application of VNP is restricted due to its reduced bioavailability and diminished brain levels that could be attributed to its low aqueous solubility, short half-life, and presystemic metabolism exposure. Accordingly, the goal of this work was to explore the ability of surface-tailored intranasal emulsomes to boost brain delivery of the drug. A 3221 factorial design was implemented to explore the impact of phospholipid (PL) to solid lipid weight ratio, PL to cholesterol molar ratio, and type of solid lipid on vesicle size, zeta potential, drug entrapment, and release efficiency of the new developed VNP emulsomes. Tailoring of the optimized emulsomal surface formulation was performed using either cationization or PEGylation approaches to boost blood–brain barrier penetration. The pharmacokinetic assessment in rats showed significantly improved bioavailability of VNP emulsomal formulations compared to the oral market product. Additionally, surface-tailored emulsomes exhibited significantly higher brain levels compared to the optimized emulsomes. Based on these findings, the proposed surface-tailored emulsomes could be considered as a promising platform for achieving high brain levels of VNP following intranasal administration.

Development of a Novel Bilosomal System for Improved Oral Bioavailability of Sertraline Hydrochloride: Formulation Design, In Vitro Characterization, and Ex Vivo and In Vivo Studies

This study was proposed to develop an optimized sertraline hydrochloride (SER)–loaded bilosomal system and evaluate its potential for enhancement of drug oral bioavailability. A full 23 factorial design was used to prepare SER-loaded bilosomal dispersions by thin film hydration using span 60, cholesterol (CHL), and sodium deoxycholate (SDC). The investigated factors included the total concentration of span 60 and CHL (X1), span 60:CHL molar ratio (X2), and SER:SDC molar ratio (X3). The studied responses were entrapment efficiency (EE%) (Y1), zeta potential (Y2), particle size (Y3), and in vitro % drug released at 2 (Y4), 8 (Y5), and 24 h (Y6). The selected optimal bilosomal dispersion (N1) composition was 0.5% w/v (X1), 1:1 (X2), and 1:2 (X3). Then, N1 was freeze dried into FDN1 that compared with pure SER for in vitro drug release, ex vivo permeation through rabbit intestine, and in vivo absorption in rats. Moreover, storage effect on FDN1 over 3 months was assessed. The optimal dispersion (N1) showed 68 ± 0.7% entrapment efficiency, − 41 ± 0.78 mV zeta potential, and 377 ± 19 nm particle size. The freeze-dried form (FDN1) showed less % drug released in simulated gastric fluids with remarkable sustained SER release up to 24 h compared to pure SER. Moreover, FDN1 showed good stability, fivefold enhancement in SER permeation through rabbit intestine, and 222% bioavailability enhancement in rats’ in vivo absorption study compared to pure SER. The SER-loaded bilosomal system (FDN1) could improve SER oral bioavailability with minimization of gastrointestinal side effects.Graphical abstract

Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies.

Colorectal cancer (CRC) is considered one of the most commonly diagnosed malignant diseases. Recently, there has been an increased focus on using nanotechnology to resolve most of the limitations in conventional chemotherapy. Niosomes have great advantages that overcome the drawbacks associated with other lipid drug delivery systems. They are simple, cheap, and highly stable nanocarriers. This study investigated the effectiveness of using niosomes with their amphiphilic characteristics in the incorporation of both hydrophilic and hydrophobic anticancer drugs for CRC treatment. Methods: Drug-free niosomes were formulated using a response surface D-optimal factorial design to study the cholesterol molar ratio, surfactant molar ratio and surfactant type effect on the particle size and Z-potential of the prepared niosomes. After numerical and statistical optimization, an optimized formulation having a particle size of 194.4 ± 15.5 nm and a Z-potential of 31.8 ± 1.9 mV was selected to be loaded with Oxaliplatin and Paclitaxel separately in different concentrations. The formulations with the highest entrapment efficiency (EE%) were evaluated for their drug release using the dialysis bag method, in vitro antitumor activity on HT-29 colon cancer cell line and apoptosis activity. Results: Niosomes prepared using d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) at a molar ratio 4, cholesterol (2 molar ratio) and loaded with 1 molar ratio of either Oxaliplatin or Paclitaxel provided nanosized vesicles (278.5 ± 19.7 and 251.6 ± 18.1 nm) with a Z-potential value (32.7 ± 1.01 and 31.69 ± 0.98 mV) with the highest EE% (90.57 ± 2.05 and 93.51 ± 2.97) for Oxaliplatin and Paclitaxel, respectively. These formulations demonstrated up to 48 h drug release and increased the in vitro cytotoxicity and apoptosis efficiency of both drugs up to twice as much as free drugs. Conclusion: These findings suggest that different formulation composition parameters can be adjusted to obtain nanosized niosomal vesicles with an accepted Z-potential. These niosomes could be loaded with either hydrophilic drugs such as Oxaliplatin or hydrophobic drugs such as Paclitaxel. Drug-loaded niosomes, as a unique nanomicellar system, could enhance the cellular uptake of both drugs, resulting in enhanced cytotoxic and apoptosis effects against HT-29 colon cancer cells. Oxaliplatin–niosomes and Paclitaxel–niosomes can be considered promising alternative drug delivery systems with enhanced bioavailability of these two anticancer drugs for colorectal cancer treatment.

Continuous supercritical CO2 assisted process for the production of nano-niosomes loaded with a second-generation antibiotic for ocular therapy

Nano-niosomes were produced by a continuous supercritical CO2 assisted process. Operating at 100 bar and 40 °C, different Span® 80 to Tween® 80 wt ratios and two surfactant to cholesterol molar ratios were tested. The 90/10 Span® 80 to Tween® 80 ratio produced the right formulation to obtain spherical and stable niosomes, with a mean diameter of 145 ± 52 nm. Adding cholesterol to niosome formulations, a general slight increase in vesicles mean size was observed and also a larger tendency to their aggregation. Ofloxacin was selected as a model drug to be loaded into nano-niosomes; the largest encapsulation efficiency of 78% and a prolonged drug release up to 5 h were measured when the 90/10 Span® 80 to Tween® 80 ratio was used in the starting formulation, in which also cholesterol, at a surfactant to cholesterol molar ratio equal to 4, was added.

A Brain-Targeted Approach to Ameliorate Memory Disorders in a Sporadic Alzheimer's Disease Mouse Model via Intranasal Luteolin-Loaded Nanobilosomes.

Impaired memory and cognitive function are the main features of Alzheimer’s disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood–brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 23-factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (−42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.

Tailoring Niosomes- Implications for Controlled Cargo Release and Function as Nanoreactors.

Nonionic surfactant vesicles (Niosomes) were prepared using polyoxyethylene alkyl ether (Brij 58).The impact of variation of the Brij: cholesterol molar ratio on the niosomal structure was studied. Fluorescence studies performed with the membrane probe 1,6-Diphenyl-1,3,5-triene (DPH) gave important insight on the bilayer integrity of the niosomes in response to environmental perturbations. The aim of the work being assessment of the efficacy of the niosomes as "drug release vehicles", release studies were performed with a xanthene dye Carboxyfluorescein (CF). Further, the vesicles were used as nanoreactors for the synthesis of gold nanoparticles (GNPs) as it is often useful to house nanoparticles in biological /biomimicking environments. Stable, spherical GNPs of diameter 6-10 nm were formed in these vesicles. As the vesicular bilayer mimics the cell membrane, the present work is relevant to the use of the GNPs for diagnostic and therapeutic purpose. It has also been established that fluorescence resonance energy transfer (FRET) effectively occurs between DPH and CF in the niosomes. The FRET studies provide important insight on the location of dyes within the vesicles thus indicating the prospective applications of this fluorescence technique for tracking the location of probes in biomimicking systems which maybe extrapolated to in vivo biological systems in future.

Olmesartan niosomes ameliorates the Indomethacin-induced gastric ulcer in rats: Insights on MAPK and Nrf2/HO-1 signaling pathway.

Gastric ulcer is a continuous worldwide threat that inquires protective agents. Olmesartan (OLM) has potent anti-oxidant and anti-inflammatory characters, yet having limited bioavailability. We targeted the gastro-protective potential and probable mechanism of OLM and its niosomal form against indomethacin (IND) induced-gastric ulcer in rats. we prepared OLM niosomes (OLM-NIO) with different surfactant: cholesterol molar ratios. We evaluated particle size, zeta-potential, polydispersity, and entrapment efficiency. In-vitro release study, Fourier transform infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy were performed for selected niosomes. In-vivo, we used oral Omeprazole (30mg/kg), OLM or OLM-NIO (10mg/kg) for 3days before IND (25mg/kg) ingestion. We assessed gastric lesions, oxidative and inflammatory markers. OLM-NIO prepared with span 60:cholesterol ratio (1:1) showed high entrapment efficiency 93 ± 2%, small particle size 159.3 ± 6.8nm, low polydispersity 0.229 ± 0.009, and high zeta-potential -35.3 ± 1.2mV, with sustained release mechanism by release data. In-vivo macroscopical and histological results showed gastro-protective effects of OLM pretreatment, which improved oxidative stress parameters and enhanced the gastric mucosal cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2) contents. OLM pretreatment suppressed interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) contents and translocation of p38 mitogen-activated protein kinase (p38-MAPK). Besides, OLM substantially promoted the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) protective pathway. OLM-NIO furtherly improved all previous outcomes. We explored OLM anti-ulcerative effects, implicating oxidative stress and inflammation improvement, mediated by the Nrf2/HO-1 signaling pathway and p38-MAPK translocation. Meanwhile, the more bioavailable OLM-NIO achieved better gastro-protective effects compared to conventional OLM form.

Gold nanoparticles loaded into niosomes: A novel approach for enhanced antitumor activity against human ovarian cancer

In the current study, gold nanoparticles (AuNPs) were prepared using the green synthesis method usingArtemisia annua extract, loaded into niosomes, and investigated their cytotoxicity and apoptotic effects. To optimize the niosomal formulation containing AuNPs, the effects of surfactants: cholesterol molar ratio, Span 60: Tween 60 M ratio, and AuNP concentration (µg/mL) were investigated. After examining the drug release profile, mathematical models were assessed to predict release kinetic. The cytotoxicity of noisome encapsulated AuNPs and free AuNPs was evaluated against human ovarian cancer cell line (A2780) by MTT assay. The apoptotic/necrosis ratio was studied using flow cytometry as well as Real-Time PCR was used for the Bax and Bcl-2 apoptosis gene expression. The results showed that the entrapment efficiency and particle size of optimized niosomal formulation encapsulated AuNPs were 34.49%±0.84 and 153.6 ± 4.62 nm with a regular spherical shape, respectively. The release profile of AuNPs from niosomal formulation was 59%±1.0 after 8 h suggesting the controlled release profile. This formulation exerted dose-dependent cytotoxicity against the A2780 cells via induction of apoptosis and significant upregulation of mRNA expression of Bax gene; while expression of anti-apoptotic gene Bcl-2 was down-regulated. Thus, the findings suggest that AuNP-loaded niosomal formulation is considered a promising and suitable targeted system for improving anti-tumor activity against A2780 cells.

Development of alendronate niosomal delivery system for gastrointestinal permeability improvement

In this study, the influences of surfactant types, the molar ratio of surfactant and cholesterol, and the molar ratio of drug load and total lipids on the size, zeta potential and drug entrapment efficiency of niosomes were statistically evaluated using a central composite design. Alendronic acid, a bisphosphonate compound was used to study. Stability, in vitro drug release and gastrointestinal permeability improvement of alendronate niosomal dispersion were also studied. The results showed that surfactant types, molar ratios of surfactant to cholesterol and molar ratios of drug load to total lipids had a significant effect on particle size, zeta potential and drug entrapment efficiency of niosomes (P < 0.05). The obtained niosomes were of a unilamellar spherical shape with negative zeta potential values. The niosomes prepared from Span 60 were larger and more entrapment efficient than those prepared from Span 20. In addition, the decrease of molar ratios of Spans and cholesterol resulted in the increase of zeta potential. The particle size and drug entrapment efficiency decrease when the molar ratio of Spans and cholesterol was decreased. Moreover, increase of drug load and total lipid molar ratio resulted in the decrease of zeta potential. However, particle size and drug entrapment efficiency could be increased with increasing molar ratio of drug loading and total lipid. Niosomes prepared from Span 60 showed a slower release rate than those prepared from Span 20. In the stability study, when stored at 4 °C for 90 days, only niosomes prepared from Span 20 have no significant change in particle size, zeta potential and the percentage of drug entrapment. The permeation of alendronate niosomes across Caco-2 cells monolayer showed that the average apparent permeability of alendronic acid from the niosomal dispersion prepared from Span 20 and Span 60 were significantly greater than that of the drug solution. This study revealed that niosomal dispersion can improve the oral bioavailability of alendronic acid.

Design, optimization, and in-vivo hypoglycaemic effect of nanosized glibenclamide for inhalation delivery

The aim of this research was the development and optimization of nanoniosomes for delivery of glibenclamide (Gbn) as hypoglycaemic agent to the lung in an inhaler dosage form. Fifteen formulae of niosomal dispersions were prepared according to Box–Behnken design. The effect of drug amount, Cholesterol molar ratio, and Hydrophilic lipophilic balance (HLB) values of the surfactant on the mean vesicle size, Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency, and in-vitro released of Gbn were investigated. A quality control check was performed on an inhaler filled with the optimum nanoniosomal formula. The in-vivo hypoglycaemic effect of nanoniosomal inhalation was also evaluated. The vesicle size observed of the optimized formula was 172 ± 4.6 nm, PDI was 0.304 ± 0.06 and ZP was −49.9 ± 1.5 mv with 69 ± 9.3% in-vitro drug release after 2 h. The Cholesterol molar ratio and the HLB value showed a statistically significant effect on dependent variables. In-vivo results proved that nanoniosomes were efficiently delivered from the inhalation canister showing a mass median aerodynamic diameter of 1.4 micron. The inhaled nanoniosomal dispersion loaded with Gbn showed a decrease in blood glucose level of hyperglycaemic rats by 51.42 ± 5.2%± after 180 min which was nearly two folds compared to oral Gbn. Gibenclamide nanoniosomes inhaler could be suggested as a novel effective dosage form for the treatment of Diabetes mellitus.