Non-ionic Surfactant Vesicles Research Articles

Recent Advances in Niosomal Drug Delivery: A Review

The production of niosomes, which are non-ionic surfactant vessels, involves hydrating synthetic non-ionic surfactants, either with or without the addition of cholesterol or another lipid. Due to their distinctive qualities, including biodegradability, biocompatibility, chemical stability, low production cost, ease of storage and handling, and low toxicity, non-ionic surfactant vesicles also known as niosomes have received a lot of attention in the field of modern drug delivery system. Niosomes are hydrated vesicular systems with a lamellar bilayer structure made of non-ionic surfactants with or without cholesterol, and they have a wide spectrum of solubilities that allow them to encapsulate a variety of bioactive chemicals. Niosomes have been tested as a delivery system for a variety of anti-cancer medications, genes, antigens, and other bioactive substances. This article focuses on recent developments in niosomal drug delivery, possible benefits over alternative delivery mechanisms, formulation techniques, characterisation techniques, and ongoing niosome research.

Preparation, Characterization and Application of Niosomes for the Delivery of Herbal Bioactive Agents: A Mini Review

The demands of herbal products including Nutraceuticals, cosmetics and drugs increased tremendously globally in recent times. Herbal compounds offer limited toxicity, high biocompatibility with numerous health benefits. The herbal drugs show many health benefits due to their presence of bioactive compounds in it. However, bioactive compounds suffer due to their poor solubility, poor bioavailability and stability. Niosomes, a non-ionic surfactant vesicle, can be a promising aspect to deliver the bioactive compound to enhance the bioavailability and stability. Niosomes have many advantages as it enables encapsulation of either hydrophilic and hydrophobic compounds. Preparation methods of niosomes are also simple and inexpensive. Moreover, encapsulating bioactive compounds in niosome not only improve the bioavailability but also enable it for sustained release or controlled release drug delivery. The review highlights various methods for niosome preparation, including thin-film hydration, reverse-phase evaporation, ether injection, microfluidization and bubble methods along with their advantages and disadvantages. Additionally, the characterization techniques, such as size determination, zeta potential measurement, and morphological evaluation, are also discussed.

Tailored Non-ionic Surfactant Vesicles of Cyclosporine for the Treatment of Psoriasis: Formulation, Ex-Vivo and In-Vivo investigation-Application of Box-Behnken Design

Tailored Non-ionic Surfactant Vesicles of Cyclosporine for the Treatment of Psoriasis: Formulation, Ex-Vivo and In-Vivo investigation-Application of Box-Behnken Design

Niosomes: A Camouflaged Carrier for Drug Delivery System

The formation of vesicles as a tool to improve the drug delivery system. Niosomes are a system aimed at delivering drugs. Niosomes of non-ionic vesicles are highly affected by the hydration of nonionic syntactants, or unmixed cholesterol or other lipids. Niosomes promise a drug delivery and non-ionic vehicle, is less toxic and improves drug treatment index by inhibiting its action to target cells and play a key role in regulating nutrient release. Niosomes are preferred over liposomes because the former exhibit high chemicalstability and economy. The application of vesicular (lipid vesicles and non-ionic surfactantvesicles) systems in cosmetics and for therapeutic purpose may offer several advantages.They improve the therapeutic performance of the drug molecules by delayed clearance from the circulation, protecting the drug from biological environment and restricting effects to target cells. This article focuses on the recent advances in niosomal drug delivery, potential advantages over other delivery systems, formulation methods, methods of characterization and the current research in the field of niosomes.

Does Trigonelline Help Skin Tone? Molecular Docking Studies of Trigonelline on the Human Tyrosinase, Formulation, Optimization and Characterization of an Emulgel Containing Trigonella foenum-graecum L. fenugreek Standardized Hydroalcoholic Extract.

This study aimed to perform molecular docking studies to identify possibilities of the inhibitory potential of the trigonelline present in fenugreek seeds on the human tyrosinase, standardize fenugreek extract, formulate, and characterize an emulgel containing fenugreek extract-entrapped niosomal vesicles. The docking study was performed using AutoDock software. The extract was standardized by the RP-HPLC method. Emulgels containing fenugreek extract and fenugreek extract-entrapped niosomes were optimized by the D-optimal method. In vitro characterization and stability studies were also carried out. The lowest energy docked poses of trigonelline on the human tyrosinase complex was calculated -5.8 kcal/mol. Also, in vitro assessment of the tyrosinase inhibitory effect of trigonelline and comparison of IC50 values of trigonelline and kojic acid revealed that the enzyme inhibition efficacy of trigonelline was stronger than that of kojic acid. Optimization led to emulgels with desired viscosity, droplet size, and spreadability values. The release study showed that trigonelline was released from the niosomes at a lower rate compared to extract containing emulgel. Permeation investigations revealed that trigonelline in niosomes has a higher ability to permeate through the skin. In conclusion, in silico and in vitro studies have shown that trigonelline can be assumed as an appropriate candidate for developing new cosmetic preparations and nonionic surfactant vesicles help trigonelline to permeate through the skin to a higher extent. However, clinical trials should be performed to confirm these findings.

Stability of Non-Ionic Surfactant Vesicles Loaded with Rifamycin S.

These days, the eradication of bacterial infections is more difficult due to the mechanism of resistance that bacteria have developed towards traditional antibiotics. One of the medical strategies used against bacteria is the therapy with drug delivery systems. Non-ionic vesicles are nanomaterials with good characteristics for encapsulating drugs, due to their bioavailability and biodegradability, which allow the drugs to reach the specific target and reduce their side effects. In this work, the antibiotic Rifamycin S was encapsulated. The rifamycin antibiotics family has been widely used against Mycobacterium tuberculosis, but recent studies have also shown that rifamycin S and rifampicin derivatives have bactericidal activity against Staphylococcus epidermidis and Staphylococcus aureus. In this work, a strain of S. aureus was selected to study the antimicrobial activity through Minimum Inhibitory Concentration (MIC) assay. Three formulations of niosomes were prepared using the thin film hydration method by varying the composition of the aqueous phase, which included MilliQ water, glycerol solution, or PEG400 solution. Niosomes with a rifamycin S concentration of 0.13 μg/g were satisfactorily prepared. Nanovesicles with larger size and higher encapsulation efficiency (EE) were obtained when using glycerol and PEG400 in the aqueous media. Our results showed that niosomes consisting of an aqueous glycerol solution have higher stability and EE across a diversity of temperatures and pHs, and a lower MIC of rifamycin S against S. aureus.

Recent Advances and Scopes In Niosomes

Nanotechnology has recently become a significant force in contemporary medicine, with therapeutic uses ranging from contrast agents for imaging to medication transporters. It has been difficult in creating payloads that are both safe and effectively delivered. Modern approaches that focus on the drug delivery system, such as Niosomes, can accomplish this. Scientists working on drug delivery systems have become more interested in the formation of non-ionic surfactant vesicles as a technique to enhance drug delivery over the past few decades. The development of Niosomes involves hydration of synthetic surfactants with the right proportions of cholesterol or other amphiphilic compounds to form self-assembled vesicular Nanocarriers. Niosomes also offer an easy manufacturing process, with low production costs, and have increased stability, thus eliminating the fundamental drawbacks of liposomes. Simple preparation techniques and commonly used surfactants in pharmaceutical technology can be employed to prepare Niosomes. This review covers composition, preparation, characterization/evaluation, benefits, limitations, applications, and recent developments of Niosomes.

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.

Intranasally administered S-MGB-364 displays antitubercular activity and modulates the host immune response to Mycobacterium tuberculosis infection.

BackgroundPreviously, we evaluated the intracellular mycobactericidal activity of the minor groove binder, S-MGB-364 against the clinical Mycobacterium tuberculosis (Mtb) strain HN878 in macrophages.ObjectivesTo assess the mycobactericidal activity of S-MGB-364 in Mtb-infected mice. Further, we investigated a plausible DNA binding mechanism of action of S-MGB-364.MethodsThe anti-TB and host immune effects of intranasal S-MGB-364 or S-MGB-364 encapsulated in non-ionic surfactant vesicles (NIV) were assessed in Mtb-infected mice by cfu enumeration, ELISA, histology, and flow cytometry. DNA binding was examined using native mass spectrometry and UV-vis thermal melt determination. S-MGB interference with DNA-centric biological events was assessed using a representative panel of Mtb and human topoisomerase I, and gyrase assays.ResultsS-MGB-364 bound strongly to DNA as a dimer, significantly increasing the stability of the DNA:S-MGB complex compared with DNA alone. Moreover, S-MGB-364 inhibited the relaxation of Mtb topoisomerase I but not the human form. In macrophages, S-MGB-364 or S-MGB-364-NIV did not cause DNA damage as shown by the low γ-H2AX expression. Importantly, in the lungs, the intranasal administration of S-MGB-364 or S-MGB-364-NIV formulation in Mtb-infected mice was non-toxic and resulted in a ∼1 log cfu reduction in mycobacterial burden, reduced the expression of proinflammatory cytokines/chemokines, altered immune cell recruitment, and importantly reduced recruitment of neutrophils.ConclusionsTogether, these data provide proof of concept for S-MGBs as novel anti-TB therapeutics in vivo.

Mucosal and systemic immune responses following mucosal immunisation of tetanus toxoid entrapped in lipid nanoparticles prepared by microwave reactor

In this study, the use of a microwave reactor, which allowed high input of energy into a pressurised system in a short period of time, was investigated for preparation of lipid nanoparticles (LNPs). The aim was to optimise the formulation process by reducing manufacturing time. Two types of LNPs were prepared; non-ionic surfactant vesicles (NISV) and bilosomes (modified NISV incorporating bile salts), with a model antigen (tetanus toxoid, TT) and the immune response induced after mucosal (nasal and oral, respectively) administration was assessed. The TT loaded LNPs were characterised in terms of particle size, size distribution, morphology, and entrapment efficiency. Immunisation was evaluated by lethal challenge with tetanus toxin in an animal model. The efficiency of vaccination was evaluated by measuring the anti-TT IgG antibody levels in the vaccinated animals. Bilosomes formed by this method showed an immunogen entrapment efficiency of ∼30% which was significantly (p < 0.05) higher than entrapment efficiency in the NISV. The percentage of animals that survived when challenged with tetanus toxin correlated with the level of IgG determined in the serum of mice immunised with LNPs by the mucosal route. Moreover, there were significant (p < 0.05) differences between orally and nasally immunised groups. Animal groups immunised bilosomes via the oral route showed the highest level of IgG (1.2 ± 0.13) compared to the positive control, LN + Xn, and no immunised group. Similarly, groups immunised via the nasal route showed significantly (p < 0.0001) higher titres compared with the control group. Mucosal TT was capable of inducing systemic specific IgG anti-TT responses that were higher than the parenteral vaccine.

A Review of Niosomes as Novel Drug Delivery Systems

The aim of this review is to present the structure of niosome, benefits and drawbacks, fundamentals of niosome preparation and characterization as well as a description of their applications in drug delivery. This review will provide an overview on the increasing interest on niosomes in the field of drug delivery. Drug delivery systems are defined as formulations aiming for transportation of a drug to the desired area of action within the body. The basic component of drug delivery systems is an appropriate carrier that protects the drug from rapid degradation or clearance and thereby enhances drug concentration in target tissues. Drug targeting is a kind of phenomenon in which drug gets distributed in the body in such a manner that the drug interacts with the target tissue at a cellular or subcellular level to achieve a desired therapeutic response at a desire site without undesirable interactions at other sites. This can be achieved by modern methods of targeting the drug delivery system such as niosomes. Niosomes are the type of non-ionic surfactant vesicles, which are biodegradable, non-toxic, more stable and inexpensive, a new approach to liposomes. Their structure similar to liposome and hence they can represent alternative vesicular systems with respect to liposomes. The niosomes have the tendency to load different type of drugs.

Potentiality of Melittin-Loaded Niosomal Vesicles Against Vancomycin-Intermediate Staphylococcus aureus and Staphylococcal Skin Infection.

BackgroundStaphylococcus aureus is an important human pathogen, especially causing skin and soft tissue infections (SSTIs). Over the decades, the infections caused by antibiotic-resistant strains have often become life-threatening. Consequently, exploration and development of competent approaches to combat these serious circumstances are urgently required.MethodsThe antibacterial activity of melittin (Mel) on S. aureus, methicillin-resistant S. aureus (MRSA) and clinical isolates of vancomycin-intermediate S. aureus (VISA) was investigated by minimum inhibitory concentration (MIC) and time-killing assays. The localization of Mel on the bacterial cell was visualized by confocal laser scanning microscopy and its effect on the membrane was indicated based on propidium iodide uptake. The non-ionic surfactant vesicle (NISV) or niosome nanocarrier was established for Mel loading (Mel-loaded NISV) by the thin-film hydration method. Physicochemical and in vitro biological properties of Mel-loaded NISVs were characterized. The cellular uptake of Mel-loaded NISVs was evaluated by holotomography analysis. In addition, an ex vivo study was conducted on a porcine ear skin model to assess the permeation ability of Mel-loaded NISVs and their potential to inhibit bacterial skin infection.ResultsThe effective inhibitory activity of Mel on skin pathogens was demonstrated. Among the tested strains, VISA was most susceptible to Mel. Regarding to its function, Mel targeted the bacterial cell envelope and disrupted cell membrane integrity. Mel-loaded NISVs were successfully fabricated with a nano-size of 120–200 nm and entrapment efficiency of greater than 90%. Moreover, Mel-loaded NISVs were taken up and accumulated in the intracellular space. Meanwhile, Mel was released and distributed throughout the cytosol and nucleus. Mel-loaded NISVs efficiently inhibited the growth of bacteria, particularly MRSA and VISA. Importantly, they not only penetrated epidermal and dermal skin layers, but also reduced the bacterial growth in infected skin.ConclusionMel-loaded NISVs have a great potential to exhibit antibacterial activity. Therapeutic application of Mel-loaded NISVs could be further developed as an alternative platform for the treatment of skin infection via dermal and transdermal delivery.

In-vitro characterization of pluronic P 123 based niosome for targeted delivery of doxorubicin

The major downside of conventional chemo-therapeutics is their lenient distribution in the body which brings about consequential knock-on to well cells. As out-turn, the concentration of drug extends to the tumor is bring down, ensuring suboptimal therapeutic efficacy. Non-ionic surfactant vesicles (niosome) were drawn up with a point of upgrading the therapeutic presence of the molecules of the drug by shielding the drug. Doxorubicin (DOX), an anti-cancer drug, from the biological environment, results in controlled drug delivery and better availability. Niosome were formulated by the method of conventional thin-film hydration using cholesterol and pluronic P123. Doxorubicin was enclosed in the niosome with an elevated entrapment efficiency of 88%. Their diameter was about 200 nm. The discharged drug by the vesicles was spotted to be managed and sustained for over 24 h at pH 7.4, followed by a Higuchi kinetic release mechanism. In closing, niosome might be an auspicious delivery for DOX with refined targeted drug delivery.

Niosomes

Niosome are non-ionic surfactant vesicles. These are obtained by hydrating combination of cholesterol and non-ionic surfactants. It is used as carrier for amphiphilic and lipophilic medicine. Niosomes are identity assemble vesicles collected largely of artificial surfactants and cholesterol. Drug delivery potential of niosomes can be enhanced in use of novel drug delivery concepts similar to proniosomes, discomes and aspasomes. By reducing the clearance the rate of noisomes they provide better help in analytic imaging and as a vaccine adjuvant. As well as they supply better support in analytic imaging and as a vaccine adjuvant. This short communication reviews the niosomes.

Nonionic surfactant vesicles as a novel drug delivery system for increasing the oral bioavailability of Ginsenoside Rb1

In the present study, a novel nonionic surfactant vesicles (NSVs) system consisting of cholesterol, Tween 80 and Span 80 was developed for the delivery of Ginsenoside Rb1 with an improved oral bioavailability. The prepared vesicles were hollow and spherically shaped with acceptable diameter (264.68 ± 4.17 nm), zeta potential (−11.58 ± 0.87 mV) and encapsulation efficiency (69.034 ± 0.045%). XRD analysis provided affirmed the encapsulation of Rb1 in the vesicles. The in vitro release profile of Rb1 from the vesicles in the two different media (double distilled water, pH 7.0, phosphate buffer solution, pH 7.4) showed statistical insignificant difference when compared with the free Ginsenoside Rb1. Notably, the pharmacokinetic analysis of optimized Ginsenoside Rb1-NSVs exhibited a higher Cmax (9.55 ± 0.5 μg/mL versus 6.22 ± 0.53 μg/mL) with 1.82-fold increase in relative oral bioavailability. Collectively, these findings revealed that the developed vesicles could be a novel alternative in improving the oral bioavailability of Ginsenoside Rb1 and extending its application in the clinical setting.

Enhanced antibacterial activity and wound healing by a novel collagen blended ZnO nanoparticles embedded niosome nanocomposites

The developments in nanotechnology can offer novel approaches capable of delivering their desired activities. The goal of this present study is to develop novel nanocomposites based on collagen (Coll) and non-ionic surfactant vesicles (niosomes (Nio)) and zinc oxide nanoparticles (ZnO NPs) to be used for rapid wound healing and as an antimicrobial agent. The ZnO NPs, niosomes, collagen and collagen-blended zinc oxide nanoparticles embedded niosomes (Coll-Nio-ZnO) nanocomposites were characterized using different techniques, such as SEM, FTIR, XRD, particle size analysis and zeta potential measurement. The ZnO nanoparticles are quasi-spherical in form, with a diameter of <100 nm. The respective average hydrodynamic size and the zeta potential of the nanocomposite are 3 μm and −42.2 ± 0.8 mV. In addition, ZnO NPs, niosomes, collagen, and nanocomposites were evaluated for their antibacterial activity against pathogenic Gram + ve and Gram –ve bacteria such as Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. They were highly sensitive to Coll-Nio-ZnO nanocomposites. The Coll-Nio-ZnO nanocomposite exhibited good cytocompatibility against normal fibroblast 3T3 cell and also facilitated faster wound healing of 3T3 cell and high potential for skin regeneration.

In-Vitro Application of Magnetic Hybrid Niosomes: Targeted siRNA-Delivery for Enhanced Breast Cancer Therapy.

Even though the administration of chemotherapeutic agents such as erlotinib is clinically established for the treatment of breast cancer, its efficiency and the therapy outcome can be greatly improved using RNA interference (RNAi) mechanisms for a combinational therapy. However, the cellular uptake of bare small interfering RNA (siRNA) is insufficient and its fast degradation in the bloodstream leads to a lacking delivery and no suitable accumulation of siRNA inside the target tissues. To address these problems, non-ionic surfactant vesicles (niosomes) were used as a nanocarrier platform to encapsulate Lifeguard (LFG)-specific siRNA inside the hydrophilic core. A preceding entrapment of superparamagnetic iron-oxide nanoparticles (FexOy-NPs) inside the niosomal bilayer structure was achieved in order to enhance the cellular uptake via an external magnetic manipulation. After verifying a highly effective entrapment of the siRNA, the resulting hybrid niosomes were administered to BT-474 cells in a combinational therapy with either erlotinib or trastuzumab and monitored regarding the induced apoptosis. The obtained results demonstrated that the nanocarrier successfully caused a downregulation of the LFG gene in BT-474 cells, which led to an increased efficacy of the chemotherapeutics compared to plainly added siRNA. Especially the application of an external magnetic field enhanced the internalization of siRNA, therefore increasing the activation of apoptotic signaling pathways. Considering the improved therapy outcome as well as the high encapsulation efficiency, the formulated hybrid niosomes meet the requirements for a cost-effective commercialization and can be considered as a promising candidate for future siRNA delivery agents.

Galactose-Modified PH-Sensitive Niosomes for Controlled Release and Hepatocellular Carcinoma Target Delivery of Tanshinone IIA

Increasing the drug tumor-specific accumulation and controlling their release is considered one of the most effective ways to increase the efficacy of drugs. Here, we developed a vesicle system that can target hepatoma and release drugs rapidly within tumor cells. This non-ionic surfactant vesicle is biodegradable. Galactosylated stearate has been used to glycosylate the vesicles to achieve liver targeting; replacement of a portion (Chol:CHEMS = 1:1) of cholesterol by cholesteryl hemisuccinate (CHEMS) allows for a rapid release of drugs in an acidic environment. In vitro release experiments confirmed that galactose-modified pH-sensitive niosomes loaded with tanshinone IIA had excellent drug release performance in acid medium. In vitro experiments using ovarian cancer cells (A2780), colon cancer cells (HCT8), and hepatoma cell (Huh7, HepG2) confirmed that the preparation had specific targeting ability to hepatoma cells compared with free drugs, and this ability was dependent on the galactose content. Furthermore, the preparation also had a more substantial inhibitory effect on tumor cells, and subsequent apoptosis assays and cell cycle analyses further confirmed its enhanced anti-tumor effect. Results of pharmacokinetic experiments confirmed that the vesicle system could significantly extend the blood circulation time of tanshinone IIA, and the larger area under the curve indicated that the preparation had a better drug effect. Thus, the results of biodistribution experiments confirmed the in vivo liver targeting ability of this preparation. Niosomes designed in this manner are expected to be a safe and effective drug delivery system for liver cancer therapy.

Andrographis paniculata-loaded niosome for wound healing application: Characterisation and in vivo analyses

Andrographis paniculata (A. paniculata) is widely used as a topical treatment due to its medicinal properties, such as anti-inflammatory, antibacterial and collagen synthesis, which are essential for the wound healing process. Non-ionic surfactant vesicles or niosomes can increase the bioavailability of poorly water-soluble drugs through a biological membrane. Therefore, A. paniculata extract was loaded into the niosome, which acts as a nanocarrier to facilitate the active compound in the delivery system. A standard Soxhlet method was used to extract A. paniculata by using water or ethanol as a solvent. Both extracts were subjected to High Pressure Liquid Chromatography (HPLC), antioxidant activity and cell culture analysis to determine the best concentration for niosome encapsulation. Niosome was prepared by proniosome-derived niosomal dispersion and homogenized for size reduction. The resulted niosome was incorporated into carbopol gel and the wound healing efficacy was analysed in vivo to evaluate the macroscopic and histology of treated rats. Extraction of A. paniculata by ethanol shows higher andrographolide content (52 ppm) and antioxidant activity at 2.5 mg/mL. Entrapment efficiency (EE) showed that the formulation 1 (0.6 mmol Span60, 0.4 mmol Cholesterol, 0.1 mmol Labrasol) had the highest EE for water and ethanol extract by 97.75% ± 1.28 and 97.21% ± 1.89, respectively. The optimized concentration of 100 ppm was loaded into niosomal gel because it stimulates the proliferation and migration of human skin fibroblast cells. Wound treated by niosomal gel containing A. paniculata ethanol extracts exhibited total recovery by 100%. Prominent collagen fibres and formation hair follicle were observed at the end of 14 days. The present study demonstrates a beneficial effect of A. paniculata-loaded niosomal gel which effectively assist in the wound healing process and protects the tissue from oxidative stress.

Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer.

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.