Non-Ionic Surfactants (NIOs) in Niosome Drug Delivery: In-Depth Review on Clinical Trials, Patents in Tuberculosis (TB) and Oncology

Targeted drug delivery systems are employed to administer pharmaceutical medication, facilitating the precise delivery of drugs to specific diseased areas. Various delivery methods utilize carriers such as antibodies, transdermal patches, biodegradable polymers, nanoparticles (NPs), liposomes, niosomes, and microspheres. Niosomes, on the other hand, represent a promising and innovative category of vesicular systems. Niosomes are vesicles formed by hydrating a combination of nonionic surfactants (NIOs) and cholesterol. These nonionic surfactant carriers serve as carriers for both lipophilic and amphiphilic drugs. In the drug delivery system using niosomes, the medication is enclosed within a vesicle. The niosomes in tuberculosis (TB) possess biodegradable and biocompatible properties, are nonimmunogenic, and demonstrate versatility in their structural composition. It is a serious and potentially contagious disease originating from the bacteria, Mycobacterium tuberculosis. In a recent update, the WHO still estimated that the number of TB cases was 9.9 million in 2022. The use of niosomes improves the treatment of TB through the use of much more advanced technology and advanced drug nanocarriers. The main aim of this review paper is to summarize the structural compositions of niosomes with silent features and various preparation methods, as well as to complete the discussion about tuberculosis and its treatment/diagnosis. Finally, the comparison of niosomes with liposomes and their current applications in treating TB with several niosomal-drug carriers and treatment with niosomal formulations was performed.

Purpose: To formulate niosomes of cyclosporine A using nonionic surfactants, and to use the attenuated total reflectance/Fourier transform infrared (ATR-FTIR) technique to explore solid/liquid interfacial phenomena as well as compatibility between active drug and pharmaceutical excipients.Methods: Niosomes of cyclosporine A were prepared using the thin-film hydration method. Cholesterol and non-ionic surfactants, including polyethylene glycol sorbitan monostearate (Tween 60) and sorbitan monostearate (Span 60), were used as excipients. The ATR-FTIR spectra of all the ingredients, their physical mixtures, and niosomal formulations were studied. The niosomes were characterized for size, polydispersivity index (PDI), zeta potential, and entrapment efficiency.Results: Six niosomal formulations (F1 – F6) were successfully developed. Niosomal formulation F2 prepared at the ratio of 6:4 surfactant to cholesterol, presented the highest entrapment efficiency of 77.28 %. The ATR-FTIR spectra of niosomal formulations did not show incompatibility. The size of the selected formulation (F2) was 1049 nm while its SEM image displayed a spherical nature of the niosomes.Conclusion: The results show that cyclosporine A can be entrapped in niosomes using non-ionic surfactants and cholesterol. Furthermore, there is no significant interaction between the ingredients of niosomes and cyclosporine A.Keywords: Cyclosporine A, Attenuated total reflectance Fourier transform infrared spectroscopy), Niosomes, Compatibility, Non-ionic surfactants

Niosomes are a vesicular carrier system comprised of a Nonionic surfactant bilayer surrounding an aqueous compartment. Niosomes are presumed to raise the intake of the poorly water-soluble drugs by M cells of Peyer's patches present in the intestine's lymphatic tissues, thereby avoiding the first-pass metabolism and increasing its oral bioavailability. Biodegradability, nonimmunogenic nature, minimal side effects, low cost, good stability, and flexibility to incorporate hydrophilic and lipophilic drugs are other advantages of niosomes. To formulate and evaluate a novel vesicular carrier system of a poorly soluble drug Lurasidone hydrochloride for the enhancement of its solubility and bioavailability. The thin-film hydration technique used to prepare Lurasidone hydrochloride loaded niosomes using different grades of nonionic surfactants like Brij, Span, and Tween. They evaluated for particle size, zeta potential, percent entrapment efficiency, in-vitro drug release, and in-vivo study. Niosomes comprised of Brij S-100 in drug: cholesterol: surfactant (1:1:1) showed particle size (1.15 ± 0.21 μm) and percent entrapment efficiency (97.02 ± 0.21%) and was selected for further studies. Various pharmacokinetic parameters like Cmax (281.27ng/ml), Tmax (5 h), and AUC (2640.197) were found to be significantly improved compared to plain drug solution. The Niosomal formulation could be the promising drug delivery system for the controlled and sustained release of Lurasidone.

Tuberculosis (TB) continues to pose a significant global health threat, with millions of new infections recorded annually. Current treatment strategies, such as Directly Observed Treatment (DOT), face challenges, including patient non-compliance and the emergence of drug-resistant TB strains. In response to these obstacles, innovative approaches utilizing inorganic/metallic nanomaterials have been developed to enhance drug delivery to target alveolar macrophages, where Mycobacterium tuberculosis resides. These nanomaterials have shown effectiveness against various strains of TB, offering benefits such as improved drug efficacy, minimized side effects, and sustained drug release at the infection site. This comprehensive review explores the applications of different metal nanoparticles, metal oxide nanoparticles, and metal-metal oxide hybrid nanoparticles in the management of TB, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. The synergistic effects of combining inorganic nanoparticles with conventional anti-TB drugs have demonstrated promising results in combating TB infections. Further research and development in this field hold great promise for overcoming the challenges faced in current TB therapy and improving patient outcomes.

Background: Nefopam Hydrochloride (NF-HCl) is a centrally acting non-opioid analgesic with limited oral bioavailability due to first-pass metabolism. To overcome this limitation and provide sustained drug release, niosomal drug delivery systems were explored. Objective: To formulate and characterize NF-HCl-loaded niosomes using Span surfactants and cholesterol via Hand Shaking Method (HSM) and Ether Injection Method (EIM), and evaluate their physicochemical and drug release properties. Methods: Twelve niosomal formulations were prepared using three non-ionic surfactants (Span 20, 40, and 60) in 1:1 and 2:1 molar ratios with cholesterol. The formulations were evaluated for entrapment efficiency (EE%), vesicle size, morphology, zeta potential, in vitro drug release, and drug release kinetics. Results: Among the formulations, PNF-9 (Span 60:CH, 1:1, EIM) showed the highest EE (58.94%), sustained drug release (58.82% over 8 hours), and a zeta potential of −64.6 mV. Drug release kinetics followed the Korsmeyer-Peppas model with an R² value of 0.9965, indicating non-Fickian diffusion. Stability studies confirmed greater retention at 4–8°C. Conclusion: The optimized NF-HCl niosomal formulation (PNF-9) prepared via EIM using Span 60 exhibited promising characteristics for sustained and targeted analgesic delivery, potentially enhancing therapeutic efficacy and patient compliance. Keywords: Niosomes, Nefopam Hydrochloride, Span 60, Entrapment Efficiency, Drug Release Kinetics, Ether Injection Method

Curcumin is a poorly water-soluble drug that is used for the treatment of inflammations, tumors, wound healing antioxidant and other diseases. In the current manuscript, it is successfully formulated into proniosome gels. The proniosomes are readily hydrated into niosomal formulations using warm water. Proniosomes were prepared using nonionic surfactants (tween 80, span 60) either solely or in combinations with cholesterol. The produced niosomal formulations were homogenous in size with vesicular sizes >343 and <1800 nm. The encapsulation efficiency percentage “EE%” of curcumin in niosomal formulations was different according to niosomal composition. It increased up to 99.74% in formulations of tween 80/Chol of 200 μmole/mL lipid concentration. Span 60/chol niosomes showed decreased curcumin EE%. Niosomal formulations showed increased SSTF and PC with enhancement ratios of more than 20-fold compared with curcumin suspension form. Kinetically, niosomes fitted to the Korsemeyer-Peppas model with non-Fickian transport according to their calculated n-values where curcumin suspension form showed Korsemeyer-Peppas kinetics with Fickian transport. Niosomal formulations deposited higher curcumin amounts in the skin compared with the suspension form. The best niosomal formulation (F9) was used for niosomal gel and emulgel fabrication. Finally, the anti-inflammatory activity of curcumin in various formulations was evaluated using a rat hind paw edema method and the % of swelling was 17.5% following 24 h in group treated with curcumin niosomal emulgel. In conclusion, this study suggests that the developed niosomal emulgel could significantly enhance the anti-inflammatory effect of curcumin and be an efficient carrier for the transdermal delivery of the drug.

Objective: The purpose of the present investigation was to develop and optimize nitrendipine loaded niosomal gel for transdermal delivery using quality by design approach.&#x0D; Methods: Niosomal formulations were developed by application of the thin-film hydration method using different ratios of span 60, cholesterol, temperature, and optimized by three factors-three levels Box-Behnken statistical design. The independent variables were non-ionic surfactant, cholesterol, and temperature, while vesicle size, polydispersity index, and entrapment efficiency were dependent variables. The nitrendipine loaded optimized formulation was incorporated into gel and evaluated for in vitro release, ex-vivo skin permeation, confocal laser scanning microscopy, and histopathological studies.&#x0D; Results: The optimized formulation showed the vesicular size of 226.1±4.36 nm, polydispersity index of 0.282±0.012, and entrapment efficiency of 95.34±3.18% with spherical morphology. The optimized niosomal gel formulation showed transdermal flux 127.60 µg/cm2h through albino Wistar rat skin. Niosomal gel was proved significantly superior by confocal laser scanning microscopy for satisfactory permeation and distribution of gel, deep into the rat skin. Furthermore, dermal safety was confirmed by histopathological studies for transdermal application.&#x0D; Conclusion: It was concluded that the developed niosomal gel overcomes the limitation of low penetration through rat skin and could be a potential nano vesicular system for transdermal delivery.

Invasive fungal infections require a long treatment schedule; however, treatment has become more cumbersome due to the development of resistance. Most antifungal moieties show systemic toxicity upon oral administration, leading to delivery of antifungal moieties via a topical route. Eberconazole (EBZ) is a BCS class II drug that has poor solubility and high permeability. It is a broad-spectrum imidazole derivative, which acts as a both fungicidal and fungistatic drug by inhibiting ergosterol synthesis. Various topical creams of EBZ are available in the market, but the lack of a proper dosing schedule and rapid removal lead to poor bioavailability. Niosomes are vesicular carriers that can entrap both hydrophilic and lipophilic drugs. Niosomal formulations have been prepared using Span20 (nonionic surfactant) and cholesterol by thin-film hydration (TFH) technique. During preformulation studies, the purity of EBZ was ascertained using FT-IR and melting point studies, while the standard calibration curve was prepared using UV-visible spectroscopy. The prepared niosomal formulations were characterized for their morphology, entrapment efficiency, particle size, and zeta potential. The formulation has shown 86 &plusmn; 0.85% entrapment efficiency, while the noisome appeared in a ring-like structure during its microscopic evaluation. Further evaluations of in vitro and in vivo release studies will be performed in the future for its efficacy and antifungal activity.

The objective of the present work was to develop drug loaded niosomal ophthalmic formulation of timolol maleate (an antiglaucomal drug) for enhanced trans-corneal drug permeation and better ocular bioavailability. Timolol loaded niosomes were prepared by thin film hydration method using rotary evapoarator and ultra-sonicated for size reducation using probe sonicator. The nano-vesicle (niosomal) formulation was optimized by selecting surfactant content, cholesterol content and sonication time as independent variables and particle (vesicle) size, drug entrapment efficiency and % drug release as response variables for optimization studies. The timolol maleate niosomal (TMN) formulation was evaluated for particle size, pH and osmolality and was found to possess the desired properties. The developed TMN formulation was studied for % cumulative in-vitro drug release using bottle rotating apparatus (electrolab) and was found to be 79.98% over 8 hr period exhibiting sustained drug release profile. The ex-vivo trans-corneal drug permeation profile of developed TMN was studied using modified franz-diffusion cell apparatus (Permegear) and the % cumulative drug permeation across freshly excised goat cornea was found to be 65.90 % in 8 hrs duration, which was approximately 1.5 times higher than the conventional eye drop formulation. The developed TMN was also proved to be isotonic and non-irritant in HET-CAM ocular irritancy test. It was therefore, concluded from above studies, that the developed timolol maleate niosomal (TMN) formulation is better than conventional eye drops due to longer corneal retention, sustained drug release and better trans-corneal drug permeation and thereby higher ocular bioavailability, hence, would need less frequent administration.Â

Diacerein is used for symptomatic relief and cartilage regeneration in osteoarthritis. Due to gastrointestinal side effects, poor aqueous solubility and low bioavailability, its clinical usage has been restricted. The objective of the present study was to enhance its dissolution profile and to attain sustained release by designing a novel delivery system based on niosomes. Five niosomal formulations (F1-F5) with non-ionic surfactant (sorbitan monostearate) and cholesterol in varying ratios of 5:5, 6:4, 7:3, 8:2 and 9:1 were developed by the reverse-phase evaporation technique. The size and polydispersivity index (PDI) were found in the range of 0.608 µm to 1.010 µm and 0.409 to 0.781, respectively. Scanning electron microscopy (SEM) of the selected formulation (F3) revealed spherical vesicles, and 79.8% entrapment was achieved with F3 (7:3). Dissolution studies using the dialysis method showed sustained release behaviour for all formulations. The optimized surfactant-to-cholesterol concentration (7:3) in formulation F3sustained the drug-release time (T50%) up to 10 hours. Kinetic modelling exhibited a zero-order release (R2=0.9834) and the release exponent 'n' of the Korsmayer-Peppas model (n=0.90) confirmed non-fickian and anomalous release. The results of this study suggest that diacerein can be successfully entrapped into niosomes using sorbitan monostearate and that these niosomes have the potential to deliver diacerein efficiently at the absorption site.

The aim of the present report was to develop nonionic surfactant vesicles (niosomes) to improve poor and variable oral bioavailability of griseofulvin. Niosomes were prepared by using different nonionic surfactants span 20, span 40, and span 60. The lipid mixture consisted of surfactant, cholesterol, and dicetyl phosphate in the molar ratio of 125:25:1.5, 100:50:1.5, and 75:75:1.5, respectively. The niosomal formulations were prepared by thin film method and ether injection method. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for size distribution and entrapment efficiency for both methods. Result indicated that the niosomes prepared by thin film method with span 60 provided higher entrapment efficiency. The niosomal formulation exhibited significantly retarded in vitro release as compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of griseofulvin in albino rats after a single oral dose. The maximum concentration (Cmax) achieved in case of niosomal formulation was approximately double (2.98 microg/ml) as compared to free drug (1.54 microg/ml). Plasma drug profile also suggested that the developed niosomal system also has the potential of maintaining therapeutic level of griseofulvin for a longer period of time as compared to free griseofulvin. The niosomal formulation showed significant increase in area under the curve0-24 (AUC; 41.56 microg/ml h) as compared to free griseofulvin (22.36 microg/ml h) reflecting sustained release characteristics. In conclusion, the niosomal formulation could be one of the promising delivery system for griseofulvin with improved oral bioavailability and prolonged drug release profiles.

The term homogenise means "to force or provide coalesce". Homogenisation is a process to attain homogenous particle size. The objective of the homogenisation process is to use fluid force to split the fragments or tiny particles contained in the fluids into very small dimensions and form a sustainable dispersion suitable for further production. The databases were collected through Scopus, google patent, science web, google scholar, PubMed on the concept of homogenisation. The data obtained were systematically investigated. The present study focus on the use of the homogenisation in drug delivery system. The aim of homogenisation process is to achieve the particle size in micro-and nano- range as it affects the different parameters in the formulation and biopharmaceutical profile of the drug. The particle size reduction plays a key role in influencing drug dissolution and absorption. The reduced particle size enhances the stability and therapeutic efficacy of the drug. Homogenization technology ensures to achieve effective, clinically efficient and targeted drug delivery with the minimal side effect. Homogenization technology has been shown to be an efficient and easy method of size reduction to increase solubility and bioavailability, stability of drug carriers. This article gives an overview of the process attributes affecting the homogenization process, the patenting of homogeniser types, design, the geometry of valves and nozzles and its role in drug delivery.

Niosome are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or their lipids. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs. Noisome are promising vehicle for drug delivery and being non-ionic; and Niosomes are biodegradable, biocompatible nonimmunogenic and exhibit flexibility in their structural characterization. Niosomes can entrap both hydrophilic and lipophilic drugs and can prolong the circulation of the entrapped drug in body. Proniosomes are dry formulation of water soluble carrier particles that are coated with surfactant. They are rehydrated to form niosomal dispersion immediately before use on agitation in hot aqueous media within minutes. Proniosomes and niosomes are physically stable during the storage and transport. Drug encapsulated in the vesicular structure of proniosomes prolong the existence of drug in the systematic circulation and enhances the penetration into target tissue and reduce toxicity. From a technical point of view, niosomes and proniosomes are promising drug carriers as they possess greater chemical stability and lack of many disadvantages associated with liposomes, such as high- cost and variable purity problems of phospholipids. The present review emphasizes on overall methods of preparation characterization and applicability of niosomes and proniosomes in targeted drug delivery. KEYWORDS: proniosomes, targeted , Niosome,

Breast cancer (BC) remains one of the significant health issues across the globe, being diagnosed in millions of women worldwide annually. Conventional therapeutic options have substantial adverse effects due to their non-specificity and limited drug bioavailability. Niosomes, being novel drug delivery systems formed from non-ionic surfactants, with or without cholesterol and charge-inducing agents, are used as therapeutic options in treating BC. Their formulation by various methods enhances the therapeutic efficacy and bioavailability and minimises side effects. Niosomal formulation of tamoxifen exhibits target drug delivery with enhanced stability, whereas docetaxel and methotrexate show sustained and controlled drug release, respectively. 5-Fluorouracil, doxorubicin, paclitaxel, cyclophosphamide and epirubicin show improved cytotoxic effects against BC when combined with other agents. Furthermore, repurposed niosomal formulations of anti-cancer drugs show improved penetration, reduced tumour volume and significantly enhanced anti-tumour effect. This review article focuses on the composition of niosomes and their application in BC treatment and then examines how niosomes could contribute to BC research.

In the last 2 decades, nanomedicine has gained enormous attention due to its promising potential in various biomedical applications such as targeted drug delivery, molecular imaging, biomarker mapping, and diagnosis. Owing to their low toxicity, and longer half-life, several nano-delivery systems such as nanoparticles, lipid carriers, dendrimers, liposomes, and micelles have been developed with unique functions and properties. With benefits such as size variability, good drug loading capacity, stable interactions, and binding with both hydrophobic and hydrophilic substances, nano-delivery systems are designed to overcome problems that are associated with conventional therapies. In the context of gastrointestinal disorders, nano-drug delivery systems are effective in improving drug efficacy, bioavailability, and sustained drug release with minimal side effects. Despite all these technological advancements, nano-delivery systems encounter potential biological barriers in the form of enzymatic degradation, pH variability, and other barriers that hinder the smooth operations of the delivery process. Targeted delivery to specific receptors, passive accumulation of nanoparticles, and pH-sensitive drug release systems are the counter strategies that researchers have been using. This overview explores the role of nano-delivery systems in the treatment of gastrointestinal disorders, focusing on their therapeutic applications and the biological barriers that may limit their efficacy. Additionally, it summarizes the current research landscape and discusses the future prospects for advancing nano-delivery technologies in the management of gastrointestinal diseases.