Laboratory study: Synthesis and optimization of nano nisomes containing Bunium persicum essential oil and investigating its toxicity on Trichomonas vaginalis parasite and HFF cell line.

The use of nanotechnology can reduce the challenges facing the use of herbal compounds in the fight against infectious agents. The aim of the present research is to produce nano niosomes containing Bunium persicum essential oil with high efficiency in the temperature and acidity of the living environment of Trichomonas vaginalis parasite and to investigate its toxicity on this parasite. First, Essential oil compounds were identified using GC-Mass. Then six niosomal formulations were made using Tween 40, 60, and 80 and cholesterol by thin film method. Three formulations that have more suitable particle size, zeta potential, and essential oil release and encapsulation efficiency were selected by MTT method to investigate the toxicity on HFF (Human foreskin fibroblasts) cell line. The formulation with lower toxicity was optimized using DSPE-mPEG(2000) polymer. Encapsulation efficiency, particle size, zeta potential, release of essential oil (in temperature and acidity similar to Trichomonas vaginalis living environment), particle morphology and toxicity of optimal formulation (on HFF and Trichomonas vaginalis) were investigated. At the end, the stability of the optimized nanoparticles was studied for 120 days. 12 chemical compounds including γ-Terpinene, Cuminic aldehyde and Para-cymene were identified Bunium persicum essential oil. The optimized formulation has a particle size of 159.73 nm, a zeta potential of -25.1 mV and an encapsulation efficiency of 63.11 %, which has a slow and continuous release at the similar temperature and acidity as Trichomonas vaginalis. Niosomal nanoparticles have a spherical shape and a smooth surface and have little toxicity on the HFF cell line. Also, the toxicity of nano niosomes containing essential oil on Trichomonas vaginalis is higher than free essential oil in all concentrations. The optimized niosomal nanoparticles have good stability because their physicochemical properties have changed very little during 120 days. In conclusion optimized Niosomal formulation containing Bunium persicum essential oil compared to free essential oil can have a higher efficiency to deal with Trichomonas parasite in laboratory conditions.

In vitro study of a new theranostic smart niosomal nanostructure for direct delivery of docetaxel via anti-PSMA aptamer.

In this study, a novel quantum dot (QD)-labeled specific anti-prostate-specific membrane antigen (PSMA) aptamer sequence was conjugated to a pH-responsive niosomal particle platform for delivery of docetaxel (DTX) components. The target cells were overexpressed PSMA. This strategy can minimize the systemic toxicity prevalent in DTX. Synthesis of pH-responsive niosomes was achieved by using thin-film hydration. The conjugation of the aptamer A10 to the niosomal particle was done via a disulfide bond. Furthermore, CdSe/ZnS QDs were fabricated using a hot-injection process, then were functionalized with mercapto propanoic acid (MPA) ligands and attached to the 3' terminal of aptamer via an Amide bind. Moreover, several characterization analyses including dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) were performed. Additionally, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and apoptosis assays, as well as fluorescence microscopy, were used to assess the performance of the fabricated system. The data revealed a homogenous round-shaped population of niosomes with an average size of 200 nm and a negative surface charge was synthesized successfully. The FTIR and XRD evaluations confirmed the fabrication of both QDs and niosomes and the bioconjugation processes. The drug release happened in a controlled manner with a pH-sensitivity feature. The cellular uptake of aptamer-conjugated particles enhanced and consequently caused more cytotoxicity of prostate cancer cells with overexpression of PSMA. Furthermore, the QDs provided an ability to trace the treatment and its uptake via the targeted tissue. Overall, this study contributed to the development of a low-risk, highly specific platform for the delivery of both therapeutics and imaging agents.

Potential Utilisation of Theobroma cacao Pod Husk Extract: Protective Capability Evaluation Against Pollution Models and Formulation into Niosomes.

Theobroma cacao L. beans have long been used for food and medicinal purposes. However, up to 52%-76% of Theobroma cacao L. fruit comprises its husk, which are regarded as waste and oftentimes thrown away. In fact, cocoa pod husks actually possess a high antioxidant capacity. Antioxidants can be used to fight free radicals that are produced by environmental pollution. In order to simulate the effects of pollution, H2O2 and cigarette smoke extract models were used respectively. However, the antioxidant properties are limited on the skin due to poor penetration. Hence, in order to increase the topical penetration, cocoa pod husk extract (CPHE) was also formulated into niosomes thereafter. CPHE was characterised using total phenolic content, total flavonoid content and three antioxidant assays. After that, cytotoxicity and cytoprotective assay were conducted on HaCaT cells, which represent the skin epidermis. CPHE was then formulated into niosomes subjected to stability and penetration studies for three months. CPHE was shown to contain 164.26 ± 1.067 mg GAE/g extract in total phenolic content and 10.72 ± 0.32 mg QCE/g extract in total flavonoid content. In addition, our results showed that CPHE possesses similar antioxidant capacity through 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, around eight-fold less through ABTS assay and approximately twelve-fold less through Ferric reducing power (FRAP) assay. The extract also showed comparable cytoprotective properties to that of standard (ascorbic acid). The niosome formulation was also able to increase the penetration compared to unencapsulated extract, as well as possess a good stability profile. This showed that CPHE, in fact, could be repurposed for other uses other than being thrown away as waste.

Formulation, Characterization, and Potential Therapeutic Implications of Encapsulated Recombinant Alpha-Luffin in Niosomes.

OBJECTIVE: The anticancer properties of recombinant α-luffin (LUF) are wellestablished. However, the cytotoxic effects of encapsulating LUF within niosomes on the SKBR3 breast cancer cell line have yet to be explored. Our study aimed to investigate whether this encapsulation strategy could improve cytotoxic effects. METHODS: Alpha-luffin was expressed, purified, and refolded. Then, this protein was utilized to craft an optimal formulation, guided by experimental design. In this work, we have explored various physicochemical properties, including particle size, polydispersity index, zeta potential, morphology, entrapment efficiency, drug release and kinetics, storage stability, and FTIR spectroscopy. Additionally, we have assessed the cellular uptake and cytotoxic effect of the optimized niosome formulation on the SKBR3 breast cancer cell line. RESULTS: The optimized niosome exhibited a mean diameter of 315±6.4 nm (DLS). Successful encapsulation of LUF into regularly shaped, spherical niosomes was achieved, with an encapsulation efficiency of 73.45±2.4%. Notably, Niosomal LUF (NLUF) exhibited significantly increased cytotoxicity against SKBR3 cells. CONCLUSION: These findings suggest that niosomes loaded with LUF hold promise as a potential treatment strategy for breast cancer.

Enhancing chemotherapeutic efficacy: Niosome-encapsulated Dox-Cis with MUC-1 aptamer.

BACKGROUND: Cancer remains a formidable global health challenge, currently affecting nearly 20 million individuals worldwide. Due to the absence of universally effective treatments, ongoing research explores diverse strategies to combat this disease. Recent efforts have concentrated on developing combined drug regimens and targeted therapeutic approaches. OBJECTIVE: This study aimed to investigate the anticancer efficacy of a conjugated drug system, consisting of doxorubicin and cisplatin (Dox-Cis), encapsulated within niosomes and modified with MUC-1 aptamers to enhance biocompatibility and target specific cancer cells. METHODS: The chemical structure of the Dox-Cis conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR) and Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (LC-Q-TOF/MS). The zeta potential and morphological parameters of the niosomal vesicles were determined through Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). In vitro assessments of cell viability and apoptosis were conducted on MUC-1 positive HeLa cells and MUC-1 negative U87 cells. RESULTS: The findings confirmed the successful conjugation of Dox and Cis within the niosomes. The Nio/Dox-Cis/MUC-1 formulation demonstrated enhanced efficacy compared to the individual drugs and their unencapsulated combination in both cell lines. Notably, the Nio/Dox-Cis/MUC-1 formulation exhibited greater effectiveness on HeLa cells (38.503 ± 1.407) than on U87 cells (46.653 ± 1.297). CONCLUSION: The study underscores the potential of the Dox-Cis conjugate as a promising strategy for cancer treatment, particularly through platforms that facilitate targeted drug delivery to cancer cells. This targeted approach could lead to more effective and personalized cancer therapies.

(S)-3-(3,4-Dihydroxybenzyl) piperazine-2,5-dione (cyclo-Gly-L-DOPA or CG-Nio-CGLD) peptide loaded in Chitosan Glutamate-Coated Niosomes as anti-Colorectal cancer activity.

BACKGROUND: Colorectal cancer (CRC), now the second most prevalent malignant tumor worldwide, is more prevalent in young adults. In recent decades, there has been progress in creating anti-colorectal cancer medications, including cytotoxic compounds. OBJECTIVES: Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of novel formulations in preventing colorectal cancer. METHODS: During this study, we assessed a new kind of niosome called cyclo-Gly-L-DOPA (CG-Nio-CGLD) made from chitosan glutamate. We evaluated the anti-colorectal cancer properties of CG-Nio-CGLD utilizing CCK-8, invasion assay, MTT assay, flow cytometry, and cell cycle analysis. The transcription of genes associated with apoptosis was analyzed using quantitative real-time PCR. At the same time, the cytotoxicity of nanomaterials on both cancer and normal cell lines was assessed using MTT assays. Novel anticancer drugs are needed to surmount existing obstacles. A recent study investigated the effectiveness of newly developed formulations in preventing colorectal cancer. RESULTS: The Nio-CGLD and CG-Nio-CGLD were spherical mean diameters of 169.12 ± 1.87 and 179.26 ± 2.17 nm, respectively. Entrapment efficiency (EE%) measurements of the Nio-CGLD and CG-Nio-CGLD were 63.12 ± 0.51 and 76.43 ± 0.34%, respectively. In the CG-Nio-CGLD group, the percentages of early, late, necrotic, and viable CL40 cells were 341.93%, 23.27%, 9.32%, and 25.48%. The transcription of the genes PP53, cas3, and cas8 was noticeably higher in the treatment group compared to the control group (P > 0.001). Additionally, the treatment group had lower BCL2 and survivin gene expression levels than the control group (P < 0.01). Additionally, CG-Nio-CGLD formulations demonstrated a biocompatible nanoscale delivery mechanism and displayed little cytotoxicity toward the CCD 841 CoN reference cell line. CONCLUSION: These findings indicate that chitosan-based noisome encapsulation may enhance the effectiveness of CG-Nio-CGLD formulations in fighting cancer.

Sonchus maritimus Extract-Loaded Niosomes Bioconjugated by Linoleic Acid in Hepatic Encephalopathy Induced by High-Fructose Diet in Albino Wistar Rats.

One of the major roles of nanotechnology in the pharmaceutical field is to provide a facility to improve drug delivery systems and design smart nanocarriers with the potential to deliver specific biomolecules to the target site for treatment. This study evaluated Sonchus maritimus-loaded niosomes (SmE-N) in hepatic encephalopathy induced by a high-fructose diet (HFD) in rats. High-performance liquid chromatography (HPLC) analysis of Sonchus maritimus extracts (SmE), the synthesis of niosomes, and their characterization were performed. For the in vivo study, 24 male rats were haphazardly divided into 4 groups (n=6) control, HFD (35%), HFD+SmE-N (50 mg/kg/day), and HFD+metformin (50 mg/kg/day). Clinical behaviors and biological markers were assessed for all groups. The in vitro results of the chromatographic analysis revealed that Sonchus maritimus contains important phenolic acids, including gallic acid, vanillic acid, chlorogenic acid, and caffeic acid, as well as diverse flavonoids, including quercetin, rutin, and naringin bioactive compounds. The niosome formulation, characterized by the encapsulation efficiency of SmE, reached up to 61.40%. The in vivo results of the HFD showed a significant change in behavior parameters, liver glycogen, transaminase enzymes, brain protein, and acetylcholine esterase levels. In addition, there was a significant increase in malondialdehyde levels and a decrease in glutathione, superoxide dismutase, and glutathione peroxidase activities in the HFD group compared to the control group. Furthermore, the histopathological observation recorded a profound modification in the liver and brain tissues of the HFD group. In contrast, the treatment with SmE-N and metformin assured a partial amelioration in the noticed parameters compared to the HFD group, but SmE-N led to a better improvement than metformin compared to the control group. In conclusion, the use of SmE-N bioconjugated by linoleic acid seems powerful in treating the complications of fructose-induced metabolic disorders due to its hepato-neuroprotective abilities.

Intranasal and intraperitoneal immunization against Brucella infection using niosome and mannosylated niosomes containing Brucella recombinant trigger factor/Bp26/Omp31 chimeric protein in a mouse model.

Purpose: Brucellosis, a zoonotic infectious disease, is a worldwide health issue affecting animals and humans. No effective human vaccine and the complications caused by the use of animal vaccines are among the factors that have prevented the eradication of the disease worldwide. However, bio-engineering technologies have paved the way for designing new targeted and highly efficacious vaccines. In this regard, the study aimed to evaluate immunity induced by mannosylated niosome containing Brucella recombinant trigger factor/Bp26/Omp31 (rTBO) chimeric protein in a mouse model. Materials and Methods: rTBO as chimeric antigen (Ag) was expressed in Escherichia coli BL21 (DE3) and, after purification, loaded on niosome and mannosylated niosome. The characteristics of the nanoparticles were assessed. The mice were immunized using rTBO, niosome, and mannosylated niosome-rTBO in intranasal and intraperitoneal routes. Serum antibodies (immunoglobulin [Ig]A, IgG, IgG1, and IgG2a) and splenocyte cytokines (interferon-gamma, interleukin [IL]-4, and IL-12) were evaluated in immunized mice. Finally, immunized mice were challenged by B. melitensis and B. abortus. A high antibody level was produced by niosomal antigen (Nio-Ag) and mannosylated noisomal antigen (Nio-Man-Ag) compared to the control after 10, 24, and 38 days of immunization. The IgG2a/IgG1 titer ratio for Nio-Man-Ag was 1.2 and 1.1 in intraperitoneal and intranasal methods and lower than one in free Ag and Nio-Ag. Cytokine production was significantly higher in the immunized animal with Ag-loaded nanoparticles than in the negative control group (p<0.05). Moreover, cytokine and antibody levels were significantly higher in the injection than in the inhalation method (p<0.05). Results: The combination of mannosylated noisome and rTBO chimeric proteins stimulate the cellular and humoral immune response and produce cytokines, playing a role in developing the protective acquired immune response in the Brucella infectious model. Also, the intraperitoneal route resulted in a successful enhancement of cytokines production more than intranasal administration. Conclusion: Designing an effective vaccine candidate against Brucella that selectively induces cellular and humoral immune response can be done by selecting a suitable nanoniosome formulation as an immunoadjuvant and recombinant protein as an immune response-stimulating Ag.

Preparation and optimization of niosome encapsulated meropenem for significant antibacterial and anti-biofilm activity against methicillin-resistant Staphylococcus aureus isolates.

Background: One of the targeted drug delivery systems is the use of nanocarriers, and one of these drug delivery systems is niosome. Niosome have a nano-vesicular structure and are composed of non-ionic surfactants. Objective: In this study, various niosome-encapsulated meropenem formulations were prepared. Subsequently, their antibacterial and anti-biofilm activities were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) strains. Methods: The physicochemical properties of niosomal formulations were characterized using a field scanning electron microscope, X-Ray diffraction, Zeta potential, and dynamic light scattering. Antibacterial and anti-biofilm activities were evaluated using broth microdilution and minimum biofilm inhibitory concentration, respectively. In addition, biofilm gene expression analysis was performed using quantitative Real-Time PCR. To evaluate biocompatibility, the cytotoxicity of niosome-encapsulated meropenem in a normal human diploid fibroblast (HDF) cell line was investigated using an MTT assay. Results: An F1 formulation of niosome-encapsulated meropenem with a size of 51.3 ± 5.84 nm and an encapsulation efficiency of 84.86 ± 3.14 % was achieved. The synthesized niosomes prevented biofilm capacity with a biofilm growth inhibition index of 69 % and significantly downregulated icaD, FnbA, Ebps, and Bap gene expression in MRSA strains (p < 0.05). In addition, the F1 formulation increased antibacterial activity by 4-6 times compared with free meropenem. Interestingly, the F1 formulation of niosome-encapsulated meropenem indicated cell viability >90 % at all tested concentrations against normal HDF cells. The results of the present study indicate that niosome-encapsulated meropenem increased antibacterial and anti-biofilm activities without profound cytotoxicity in normal human cells, which could prove useful as a good drug delivery system.

Synthesis, Characterization, and In-Vitro Evaluation of Silibinin-loaded PEGylated Niosomal Nanoparticles: Potential Anti-Cancer Effects on SW480 Colon Cancer Cells.

OBJECTIVE: Colorectal cancer is a significant global health concern with high mortality rates. Silibinin is a compound derived from milk thistle with anticancer properties and may be a potential treatment option for colorectal cancer. Its poor solubility limits its clinical application, but various strategies, such as nanoparticle encapsulation, have shown promise. In this study, a PEGylated niosomal drug delivery system was used to enhance the solubility of silibinin, and its anti-proliferative effects were evaluated against human colorectal cancer cell lines. METHODS: The silibinin-loaded PEGylated niosomal nanoparticles (NIO-SIL) were fabricated using the thin-film hydration method and characterized with dialysis bag, AFM, SEM, DLS, and FTIR systems. Finally, the cancerous cells and human normal cells were treated with NIO-SIL and pure silibinin. The proliferation, apoptosis, and cell cycle of these cells were evaluated. Subsequently, the expression of Bax, Bcl-2, p53, and cyclin D1 genes was measured using real-time PCR. RESULT: The drug release profile, size, morphology, and chemical interactions of the synthesized PEGylated niosomal nanoparticles were suitable for use as a drug delivery system. Both pure silibinin and NIO-SIL could reduce the proliferation of cancerous cells, induce apoptosis, and cause cell cycle arrest, with no significant negative effects reported on human normal cells. Both pure silibinin and NIO-SIL reduced the expression of the Bcl-2 and cyclin D1 genes while increasing the expression of Bax and p53. (p-value < 0.05 *). CONCLUSION: The outcomes of this study indicate the high potential of PEGylated niosomal nanoparticles for encapsulation and delivery of silibinin to cancer cells, with no negative effects on normal cells.

Formulation, preparation of niosome loaded zinc oxide nanoparticles and biological activities.

In this study, zinc oxide nanoparticles (Zn-NPs) were prepared by the green synthesis method and loaded inside niosomes as a drug release system and their physicochemical and biological properties were determined. Zn-NPs were prepared by the eco-friendly green strategy, the structure, and morphological properties were studied and loaded into niosomes. Subsequently, different formulations of niosomes containing Zn-NPs were prepared and the optimal formulation was used for biological studies. Scanning electron microscope (SEM) and dynamic light scattering (DLS) were used to investigate the morphology and size of nanoparticles. Fourier transform infrared spectroscopy (FTIR) and UV-Vis were used to confirm the synthesis of Zn-NPs. Energy dispersive X-ray spectrometer (EDS) determined the elemental analysis of the Zn-NPs synthesis solution and the crystalline structure of Zn-NPs was analysed by XRD (X-Ray diffraction). Furthermore, Zn-NPs were loaded inside the niosomes, and their structural characteristics, entrapment efficiency (EE%), the release profile of Zn-NPs, and their stability also were assessed. Moreover, its antimicrobial properties against some microbial pathogens, its effect on the expression of biofilm genes, and its anticancer activity on the breast cancer cell lines were also determined. To study the cytocompatibility, exposure of niosomes against normal HEK-293 cells was carried out. In addition, the impact of niosomes on the expression of genes involved in the apoptosis (Bcl2, Casp3, Casp9, Bax) at the mRNA level was measured. Our findings revealed that the Zn-NPs have a round shape and an average size of 27.60 nm. Meanwhile, UV-Vis, FTIR, and XRD results confirmed the synthesis of Zn-NPs. Also, the EE% and the size of the optimized niosomal formulation were 31.26% and 256.6 ± 12 nm, respectively. The release profile showed that within 24 h, 26% of Zn-NPs were released from niosomes, while in the same period, 99% of free Zn-NPs were released, which indicates the slow release of Zn-NPs from niosomes. Antimicrobial effects exhibited that niosomes containing Zn-NPs had more significant antimicrobial and anti-biofilm effects than Zn-NPs alone, the antimicrobial and anti-biofilm effects increased 2 to 4 times. Cytotoxic effects indicated that when Zn-NPs are loaded into niosomes, the anticancer activity increases compared to Zn-NPs alone and has low cytotoxicity on cancer cells. Niosomes containing ZnNPs increased the apoptosis-related gene expression level and reduced the Bcl2 genes. In general, the results show that niosomes can increase the biological effects of free Zn-NPs and therefore can be a suitable carrier for targeted delivery of Zn-NPs.

Codelivery of methotrexate and silibinin by niosome nanoparticles for enhanced chemotherapy of CT26 colon cancer cells.

Colon cancer (CC) is one of the most prevalent cancers in the world, and chemotherapy is widely applied to combat it. However, chemotherapy drugs have severe side effects and emergence of multi drug resistance (MDR) is common. This bottleneck can be overcome by niosome nanocarriers that minimize drug dose/toxicity meanwhile allow co-loading of incompatible drugs for combination therapy. In this research, silibinin (Sil) as a hydrophobic drug was loaded into the lipophilic part, and methotrexate (MTX) into the hydrophilic part of niosome by the thin film hydration (TFH) method to form Nio@MS NPs for CT26 colon cancer therapyin vitro. Our results indicated synthesis of ideal niosome nanoparticles (NPs) with spherical morphology, size of ∼100 nm, and a zeta potential of -10 mV. The IC50value for Nio@MS was determined ∼2.6 µg ml-1, which was significantly lower than MTX-Sil (∼6.86 µg ml-1), Sil (18.46 µg ml-1), and MTX (9.8 µg ml-1). Further, Nio@MS significantly reduced cell adhesion density, promoted apoptosis and increased gene expression level of caspase 3 and BAX while promoted significant downregulation of BCL2. In conclusion, the design and application of niosome to co-administer Sil and MTX can increase the drugs cytotoxicity, reduce their dose and improve anti-cancer potential by combating MDR.

Antibacterial and antibiofilm potentials of vancomycin-loaded niosomal drug delivery system against methicillin-resistant Staphylococcus aureus (MRSA) infections.

The threat of methicillin-resistant Staphylococcus aureus (MRSA) is increasing worldwide, making it significantly necessary to discover a novel way of dealing with related infections. The quick spread of MRSA isolates among infected individuals has heightened public health concerns and significantly limited treatment options. Vancomycin (VAN) can be applied to treat severe MRSA infections, and the indiscriminate administration of this antimicrobial agent has caused several concerns in medical settings. Owing to several advantageous characteristics, a niosomal drug delivery system may increase the potential of loaded antimicrobial agents. This work aims to examine the antibacterial and anti-biofilm properties of VAN-niosome against MRSA clinical isolates with emphasis on cytotoxicity and stability studies. Furthermore, we aim to suggest an effective approach against MRSA infections by investigating the inhibitory effect of formulated niosome on the expression of the biofilm-associated gene (icaR). The thin-film hydration approach was used to prepare the niosome (Tween 60, Span 60, and cholesterol), and field emission scanning electron microscopy (FE-SEM), an in vitro drug release, dynamic light scattering (DLS), and entrapment efficiency (EE%) were used to investigate the physicochemical properties. The physical stability of VAN-niosome, including hydrodynamic size, polydispersity index (PDI), and EE%, was analyzed for a 30-day storage time at 4 °C and 25 °C. In addition, the human foreskin fibroblast (HFF) cell line was used to evaluate the cytotoxic effect of synthesized niosome. Moreover, minimum inhibitory and bactericidal concentrations (MICs/MBCs) were applied to assess the antibacterial properties of niosomal VAN formulation. Also, the antibiofilm potential of VAN-niosome was investigated by microtiter plate (MTP) and real-time PCR methods. The FE-SEM result revealed that synthesized VAN-niosome had a spherical morphology. The hydrodynamic size and PDI of VAN-niosome reported by the DLS method were 201.2 nm and 0.301, respectively. Also, the surface zeta charge of the prepared niosome was - 35.4 mV, and the EE% ranged between 58.9 and 62.5%. Moreover, in vitro release study revealed a sustained-release profile for synthesized niosomal formulation. Our study showed that VAN-niosome had acceptable stability during a 30-day storage time. Additionally, the VAN-niosome had stronger antibacterial and anti-biofilm properties against MRSA clinical isolates compared with free VAN. In conclusion, the result of our study demonstrated that niosomal VAN could be promising as a successful drug delivery system due to sustained drug release, negligible toxicity, and high encapsulation capacity. Also, the antibacterial and anti-biofilm studies showed the high capacity of VAN-niosome against MRSA clinical isolates. Furthermore, the results of real-time PCR exhibited that VAN-niosome could be proposed as a powerful strategy against MRSA biofilm via down-regulation of icaR gene expression.

Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retina-derived RPE cell line.

AIM: To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line. METHODS: Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of VEGF-A and PDGF-A, PDGF-B, PDGF-C, PDGF-D genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR). RESULTS: The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC50) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D after treatment with both free and niosomal AUR. CONCLUSION: Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

Investigation Cytotoxicity and Curcumin Release Behavior by Pyranopyrazole-TiO2@niosome Carrier for Breast Cancer Treatment.

In the present study, we present a pyranopyrazole-TiO2 which is encapsulated with a niosome as nanocarrier for delivery of curcumin into breast cancer cells. Nanocarrier porous TiO2 is biocompatible and with a high specific surface area and a large pore volume and was used to carry pyranopyrazole, which has been reported as an anti-cancer. Niosome in the outer layer, helpful for loading curcumin into the niosomal layer, demonstrates a pH-dependent release and can be effective for cancer treatment. Entrapment efficiency of curcumin was found at 81.02% in carriers. The results of MTT and flow cytometry revealed that apoptosis is notably enhanced by loading curcumin on pyranopyrazole-TiO2@niosome. Also, there was high biocompatibility with MCF-10A, while exhibiting significant anti-cancer and anti-metastatic effects on MCF-7, whose cell viability was 38.79% in the loaded curcumin on carrier and was more than other samples even, than free curcumin (42.82%). Furthermore, the regulation of gene expression in cancer cells decreased the regulation of MMP-2 and MMP-9 genes and increased the expression of caspase-3 and caspase-9 genes. Finally, fluorescence activity in MCF-7 significantly increased after treatment with samples.

Niosome-Based Hydrogel of Quince Extract: A Promising Strategy for Expedited Full-thickness Wound Healing in Rat.

BACKGROUND: The regeneration of tissue damage involves a series of molecular and cellular events that can be mediated by various natural compounds. Recent studies have highlighted the anti-inflammatory, anti-ulcer, and skin-protecting properties of Cydonia oblonga (Quince), which are mainly attributed to phenolic compounds. These compounds may have some drawbacks when targeting wound applications, including low bioavailability at the wound site. Moreover, to overcome these limitations, surfactant-based nanovesicular systems have been developed as carriers of such compounds for wound healing. OBJECTIVE: This study aimed to highlight the possible therapeutic potential of niosome-based hydrogel from Quince extract to stabilize and deliver the related bioactive compounds to full-thickness wounds in rats. METHODS: The niosomal hydrogel was prepared using a thin-film hydration method with the fruit extract (70% methanol). The formulation was optimized by evaluating size, zeta potential, dispersion index, and drug encapsulation efficiency. Full-thickness wounds were created on the dorsal cervical area of Wistar rats, and histopathological analysis of biopsy specimens was conducted on the 12th day of treatment. RESULTS: Under the study conditions, niosomal hydrogel displayed good physicochemical stability. Histopathological findings demonstrated that niosomal gel promoted angiogenesis, fibroblast maturation, collagen deposition, keratinization, and epidermal layer formation more effectively than control and hydrogel base. Furthermore, niosomal gel treatment markedly reduced inflammation. The total phenol concentration was determined to be 13.34 ± 0.90 mg gallic acid equivalents per gram of dried extract. CONCLUSION: The niosomal hydrogel containing C. oblonga extract shows potential as a novel approach for wound healing, warranting further investigation in this field.

Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.

BACKGROUND: This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. METHOD: Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. RESULTS: The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. CONCLUSIONS: The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

Development of New Nanoniosome Carriers for Vorinostat: Evaluation of Anticancer Efficacy In Vitro.

Vorinostat (VST) is a chemotherapeutic agent administrated for various types of cancers. However, it suffers from side effects and chemoresistance that reduce its application. Different nanoniosomes comprised Span 20, 60, 65 and 80 were prepared by the thin film hydration method and loaded with VST. The nanoniosomes were physicochemically characterized using particle size analysis and field emission scanning electron microscopy. The best formulation that was prepared using Span 65 (VST-NN-S65) included vesicle size of 127 nm with a narrow size distribution. VST-NN-S65 had an entrapment efficiency and loading capacity of 81.3 ± 5.1 and 32.0 ± 3.9 %, respectively. Drug release rate measurements showed that 90 % of VST was liberated within 1 h. Cytotoxicity assessments of VST-NN-S65 in HeLa and MCF7 cells indicated significant improvement in the effectiveness of VST, compared to the VST suspension. For VST-NN-S65, IC50 values of 26.3 and 6.6 µg mL-1 were obtained for HeLa and MCF7 cell lines, respectively. In situ apoptosis detection by the TUNEL assay revealed that apoptosis mainly occurred in the cell lines.

Exploring the potential of silymarin-loaded nanovesicles as an effective drug delivery system for cancer therapy: in vivo, in vitro, and in silico experiments.

We aimed to perform a comprehensive study on the development and characterization of silymarin (Syl)-loaded niosomes as potential drug delivery systems. The results demonstrate significant novelty and promising outcomes in terms of morphology, size distribution, encapsulation efficiency, in vitro release behavior, free energy profiles of Syl across the niosome bilayer, hydrogen bonding interactions, antimicrobial properties, cytotoxicity, and in vivo evaluations. The physical appearance, size, and morphology assessment of free niosomes and Syl-loaded niosomes indicated stable and well-formed vesicular structures suitable for drug delivery. Transmission electron microscopy (TEM) analysis revealed spherical shapes with distinct sizes for each formulation, confirming uniform distribution. Dynamic light scattering (DLS) analysis confirmed the size distribution results with higher polydispersity index for Syl-loaded niosomes. The encapsulation efficiency of Syl in the niosomes was remarkable at approximately 91%, ensuring protection and controlled release of the drug. In vitro release studies showed a sustained release profile for Syl-loaded niosomes, enhancing therapeutic efficacy over time. Free energy profiles analysis identified energy barriers hindering Syl permeation through the niosome bilayer, emphasizing challenges in drug delivery system design. Hydrogen bonding interactions between Syl and niosome components contributed to energy barriers, impacting drug permeability. Antimicrobial assessments revealed significant differences in inhibitory effects against S. aureus and E. coli. Cytotoxicity evaluations demonstrated the superior tumor-killing potential of Syl-loaded niosomes compared to free Syl. In vivo studies indicated niosome formulations' safety profiles in terms of liver and kidney parameters compared to bulk Syl, showcasing potential for clinical applications. Overall, this research highlights the promising potential of Syl-loaded niosomes as effective drug delivery systems with enhanced stability, controlled release, and improved therapeutic outcomes.

Synergistic activity of crocin and crocin loaded in niosomes alone and in combination with fluconazole against Candida albicans isolates: In vitro and in silico study.

INTRODUCTION: Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates. MATERIAL AND METHODS: NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties. RESULTS: NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase. CONCLUSION: The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.