Nanodelivery Approaches of Phytoactives for Skin Cancers: Current and Future Perspectives.

In recent years, there has been an increase in skin cancers due to external factors, especially environmental factors, and studies on treatment alternatives have gained importance. Nanomaterials are common, from sunscreen formulas to formulations designed to treat skin cancers at various stages. Using bioactives has multiple effects in treating skin cancers, which provides many advantages. In this regard, many phytochemicals gain importance with their antioxidant, anti-proliferative, anti-inflammatory, antiangiogenic, and analgesic effects. Their delivery with nanocarriers is on the agenda for phytochemicals to gain the targeted stability, effectiveness, and toxicity/safety properties. This review presents types of skin cancers, phytochemicals effective in skin cancers, and their nanocarrier-loaded studies from an up-to-date perspective.

Vesicular Drug Delivery Systems: Promising Approaches in Ocular Drug Delivery.

Ocular drug delivery poses unique challenges due to the complex anatomical and physiological barriers of the eye. Conventional dosage forms often fail to achieve optimal therapeutic outcomes due to poor bioavailability, short retention time, and off-target effects. In recent years, vesicular drug delivery systems have emerged as promising solutions to address these challenges. Vesicular systems, such as liposome, niosome, ethosome, transfersome, and others (bilosome, transethosome, cubosome, proniosome, chitosome, terpesome, phytosome, discome, and spanlastics), offer several advantages for ocular drug delivery. These include improved drug bioavailability, prolonged retention time on the ocular surface, reduced systemic side effects, and protection of drugs from enzymatic degradation and dilution by tears. Moreover, vesicular formulations can be engineered for targeted delivery to specific ocular tissues or cells, enhancing therapeutic efficacy while minimizing off-target effects. They also enable the encapsulation of a wide range of drug molecules, including hydrophilic, hydrophobic, and macromolecular drugs, and the possibility of combination therapy by facilitating the co-delivery of multiple drugs. This review examines vesicular drug delivery systems, their advantages over conventional drug delivery systems, production techniques, and their applications in management of ocular diseases.

A new approach for the treatment of Alzheimer's disease: insulin-quantum dots.

The potential use of insulin supplementation for Alzheimer's Disease (AD) was aimed to investigate and explore CQDs as an alternative delivery system. CQDs were produced by microwave and characterised. Insulin-loaded Ins-CQDs and in-situ Gel-Ins-CQDs were developed. The in vitro release kinetics, penetrations of insulin through excised sheep nasal mucosa were determined. Toxicity of CQDs were calculated on SH-SY5Y cells. The stability and usability of the prepared formulations were assessed. The insulin release from the solution was 70.75% after 3 hours, while it was 37.51% for in-situ Gel-Ins-CQDs. IC50 value was 52 µM. The mean particle diameters of Ins-CQDs and in-situ Gel-Ins-CQDs varied between 8.35 ± 0.19 to 8.75 ± 0.03 nm during a 6-month period. Zeta potentials ranged from -31.51 ± 1.39 to -24.43 ± 0.26 mV, and PDI values were between 9.8 ± 0.01 to 5.3 ± 3.2%(SD, n = 3) for Ins-CQDs and in-situ Gel-Ins-CQDs, respectively.Our results show that Gel-Ins-CQDs represented a controlled release over time and can be used for AD through the nasal route.

Determination of the Toxicity Preferences of Ocular Drug Delivery System by Comparing Two Different Toxicity Bioassays.

Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol®ATO5, and Pluronic® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays.

Systematic Screening Study for the Selection of Proper Stabilizers to Produce Physically Stable Canagliflozin Nanosuspension by Wet Milling Method.

One of the crucial approaches to managing the low solubility and weak bioavailability of drugs is via nanocrystal technology. Through this technology, drug particles have an increased solubility and a faster dissolution rate due to high surface free energy, which requires an appropriate stabilizer(s) to prevent instabilities during the manufacturing process and storage of the nanosuspension. This study aimed to establish a scientific predictive system for properly selecting stabilizers or to reduce the attempts on a trial-and-error basis in the wet-milling method. In total, 42 experiments were performed to examine the effect of critical material attributes on the wettability of the drug, the saturation solubility in the stabilizer solutions or combinations thereof and the dynamic viscosity of stabilizer solutions. All data were evaluated by Minitab 19® and an optimization study was performed. The optimized formulation at a certain concentration of stabilizer combination was ground by Dyno Mill® with 0.3 mm beads for one hour. The optimized nanosuspension with a particle size of 204.5 nm was obtained in short milling time and offered 3.05- and 3.51 times better dissolution rates than the marketed drug product (Invokana® 100 mg) in pH 4.5 and pH 6.8 as non-sink conditions, respectively. The formulation was monitored for three months at room temperature and 4 °C. The parameters were 261.30 nm, 0.163, -14.1 mV and 261.50 nm, 0.216 and -17.8 mV, respectively. It was concluded that this approach might indicate the appropriate selection of stabilizers for the wet-milling process.

Polymeric-Micelle-Based Delivery Systems for Nucleic Acids.

Nucleic acids can modulate gene expression specifically. They are increasingly being utilized and show huge potential for the prevention or treatment of various diseases. However, the clinical translation of nucleic acids faces many challenges due to their rapid clearance after administration, low stability in physiological fluids and limited cellular uptake, which is associated with an inability to reach the intracellular target site and poor efficacy. For many years, tremendous efforts have been made to design appropriate delivery systems that enable the safe and effective delivery of nucleic acids at the target site to achieve high therapeutic outcomes. Among the different delivery platforms investigated, polymeric micelles have emerged as suitable delivery vehicles due to the versatility of their structures and the possibility to tailor their composition for overcoming extracellular and intracellular barriers, thus enhancing therapeutic efficacy. Many strategies, such as the addition of stimuli-sensitive groups or specific ligands, can be used to facilitate the delivery of various nucleic acids and improve targeting and accumulation at the site of action while protecting nucleic acids from degradation and promoting their cellular uptake. Furthermore, polymeric micelles can be used to deliver both chemotherapeutic drugs and nucleic acid therapeutics simultaneously to achieve synergistic combination treatment. This review focuses on the design approaches and current developments in polymeric micelles for the delivery of nucleic acids. The different preparation methods and characteristic features of polymeric micelles are covered. The current state of the art of polymeric micelles as carriers for nucleic acids is discussed while highlighting the delivery challenges of nucleic acids and how to overcome them and how to improve the safety and efficacy of nucleic acids after local or systemic administration.

Development of an Antiviral Ion-Activated In Situ Gel Containing 18ß-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus.

The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18ß-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% w/w gellan gum and 0.5% w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC50) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC50 = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC50 = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication.

Biopolymer-Based Nanogel Approach in Drug Delivery: Basic Concept and Current Developments.

Due to their increased surface area, extent of swelling and active substance-loading capacity and flexibility, nanogels made from natural and synthetic polymers have gained significant interest in scientific and industrial areas. In particular, the customized design and implementation of nontoxic, biocompatible, and biodegradable micro/nano carriers makes their usage very feasible for a range of biomedical applications, including drug delivery, tissue engineering, and bioimaging. The design and application methodologies of nanogels are outlined in this review. Additionally, the most recent advancements in nanogel biomedical applications are discussed, with particular emphasis on applications for the delivery of drugs and biomolecules.

A Novel Semi-Solid Self-Emulsifying Formulation of Aprepitant for Oral Delivery: An In Vitro Evaluation.

Aprepitant is the first member of a relatively new antiemetic drug class called NK1 receptor antagonists. It is commonly prescribed to prevent chemotherapy-induced nausea and vomiting. Although it is included in many treatment guidelines, its poor solubility causes bioavailability issues. A particle size reduction technique was used in the commercial formulation to overcome low bioavailability. Production with this method consists of many successive steps that cause the cost of the drug to increase. This study aims to develop an alternative, cost-effective formulation to the existing nanocrystal form. We designed a self-emulsifying formulation that can be filled into capsules in a melted state and then solidified at room temperature. Solidification was achieved by using surfactants with a melting temperature above room temperature. Various polymers have also been tested to maintain the supersaturated state of the drug. The optimized formulation consists of CapryolTM 90, Kolliphor® CS20, Transcutol® P, and Soluplus®; it was characterized by DLS, FTIR, DSC, and XRPD techniques. A lipolysis test was conducted to predict the digestion performance of formulations in the gastrointestinal system. Dissolution studies showed an increased dissolution rate of the drug. Finally, the cytotoxicity of the formulation was tested in the Caco-2 cell line. According to the results, a formulation with improved solubility and low toxicity was obtained.

Nanofibers in Ocular Drug Targeting and Tissue Engineering: Their Importance, Advantages, Advances, and Future Perspectives.

Nanofibers are frequently encountered in daily life as a modern material with a wide range of applications. The important advantages of production techniques, such as being easy, cost effective, and industrially applicable are important factors in the preference for nanofibers. Nanofibers, which have a broad scope of use in the field of health, are preferred both in drug delivery systems and tissue engineering. Due to the biocompatible materials used in their construction, they are also frequently preferred in ocular applications. The fact that they have a long drug release time as a drug delivery system and have been used in corneal tissue studies, which have been successfully developed in tissue engineering, stand out as important advantages of nanofibers. This review examines nanofibers, their production techniques and general information, nanofiber-based ocular drug delivery systems, and tissue engineering concepts in detail.

Loteprednol-Loaded Nanoformulations for Corneal Delivery by Quality-by-Design Concepts: Optimization, Characterization, and Anti-inflammatory Activity.

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye.

Development of lipid nanoparticles for transdermal loteprednol etabonate delivery.

AIM: Loteprednol etabonate (LE) is a new generation corticosteroid that is used for the treatment of inflammatory and allergic conditions of the eye. Therefore, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were attempted to improve transdermal LE delivery for the first time. METHODS: SLN and NLC were produced by hot homogenisation and ultrasonication technique. Their physical stability was monitored for 3 months of storage. Drug release and permeation of SLN and NLC through the porcine skin were investigated. RESULTS: It was determined that SLN and NLC mean particle size of 139.1 nm had a homogeneous particle size distribution (∼0.169 PI) and the mean charge was -23.6. They were found to be stable both physically and chemically at room temperature. CONCLUSION: SLN and NLC formulations of LE can be stated among the systems that can be an alternative to conventional systems with fewer side-effects in the treatment of inflammatory problems.

Optimization of the Micellar-Based In Situ Gelling Systems Posaconazole with Quality by Design (QbD) Approach and Characterization by In Vitro Studies.

BACKGROUND: Fungal ocular infections can cause serious consequences, despite their low incidence. It has been reported that Posaconazole (PSC) is used in the treatment of fungal infections in different ocular tissues by diluting the oral suspension, and successful results were obtained despite low ocular permeation. Therefore, we optimized PSC-loaded ocular micelles and demonstrated that the permeation/penetration of PSC in ocular tissues was enhanced. METHODS: The micellar-based in situ gels based on the QbD approach to increase the ocular bioavailability of PSC were developed. Different ratios of Poloxamer 407 and Poloxamer 188 were chosen as CMAs. Tsol/gel, gelling capacity and rheological behavior were chosen as CQA parameters. The data were evaluated by Minitab 18, and the formulations were optimized with the QbD approach. The in vitro release study, ocular toxicity, and anti-fungal activity of the optimized formulation were performed. RESULTS: Optimized in situ gel shows viscoelastic property and becomes gel form at physiological temperatures even when diluted with the tear film. In addition, it has been shown that the formulation had high anti-fungal activity and did not have any ocular toxicity. CONCLUSIONS: In our previous studies, PSC-loaded ocular micelles were developed and optimized for the first time in the literature. With this study, the in situ gels of PSC for ocular application were developed and optimized for the first time. The optimized micellar-based in situ gel is a promising drug delivery system that may increase the ocular permeation and bioavailability of PSC.

Posaconazole micelles for ocular delivery: in vitro permeation, ocular irritation and antifungal activity studies.

Posaconazole (PSC) is a triazole group anti-fungal agent with the widest spectrum. Although there is no commercially available ocular dosage form, its diluted oral suspension preparation (Noxafil®) is used as off-label in topical treatment of severe keratitis and sclerokeratitis in the clinic. However, ocular bioavailability of PSC suspension form is extremely low due to its highly lipophilic character. Thus, there is a clinical need to improve its ocular bioavailability and to develop novel delivery system for the treatment of ocular fungal infections. Herein, we studied ex vivo permeation, penetration, anti-fungal activity, and Hen's Egg Test-Chorioallantoic Membrane (HET-CAM) toxicity tests in order to assess ocular targeting of PSC micelles, which were optimized in our previous study. The results indicated that micellar carrier system increased the permeability of PSC to eye tissues. Micelles showed higher affinity to ocular tissues than that of commercial oral suspension of PSC (Noxafil®). In vitro anti-fungal activity data also confirmed the efficacy of PSC loaded micellar formulations against Candida. albicans strains. The relative safety of the optimized micelles on the ocular tissue was shown with the HET-CAM toxicity test. In conclusion, micellar systems could be a promising strategy for the effective and safe delivery of PSC in the treatment of ocular fungal infections.

In Vitro Evaluation of a Solid Supersaturated Self Nanoemulsifying Drug Delivery System (Super-SNEDDS) of Aprepitant for Enhanced Solubility.

Aprepitant (APR) belongs to Class II of the Biopharmaceutical Classification System (BCS) because of its low aqueous solubility. The objective of the current work is to develop self-nanoemulsifying drug delivery systems (SNEDDS) of APR to enhance its aqueous solubility. Preformulation studies involving screening of excipients for solubility and emulsification efficiency were carried out. Pseudo ternary phase diagrams were constructed with blends of oil (Imwitor® 988), cosolvent (Transcutol® P), and various surfactants (Kolliphor® RH40, Kolliphor® ELP, Kolliphor® HS15). The prepared SNEDDS were characterized for droplet size and nanoemulsion stability after dilution. Supersaturated SNEDDS (super-SNEDDS) were prepared to increase the quantity of loaded APR into the formulations. HPMC, PVP, PVP/VA, and Soluplus® were used as polymeric precipitation inhibitors (PPI). PPIs were added to the formulations at 5% and 10% by weight. The influence of the PPIs on drug precipitation was investigated. In vitro lipolysis test was carried out to simulate digestion of formulations in the gastrointestinal tract. Optimized super-SNEDDS were formulated into free-flowing granules by adsorption on the porous carriers such as Neusilin® US2. In vitro dissolution studies of solid super-SNEDDS formulation revealed an increased dissolution rate of the drug due to enhanced solubility. Consequently, a formulation to improve the solubility and potentially bioavailability of the drug was developed.

Estimating the Optimal Dexketoprofen Pharmaceutical Formulation with Machine Learning Methods and Statistical Approaches.

OBJECTIVES: Orally disintegrating tablets (ODTs) can be utilized without any drinking water; this feature makes ODTs easy to use and suitable for specific groups of patients. Oral administration of drugs is the most commonly used route, and tablets constitute the most preferable pharmaceutical dosage form. However, the preparation of ODTs is costly and requires long trials, which creates obstacles for dosage trials. The aim of this study was to identify the most appropriate formulation using machine learning (ML) models of ODT dexketoprofen formulations, with the goal of providing a cost-effective and timereducing solution. METHODS: This research utilized nonlinear regression models, including the k-nearest neighborhood (k-NN), support vector regression (SVR), classification and regression tree (CART), bootstrap aggregating (bagging), random forest (RF), gradient boosting machine (GBM), and extreme gradient boosting (XGBoost) methods, as well as the t-test, to predict the quantity of various components in the dexketoprofen formulation within fixed criteria. RESULTS: All the models were developed with Python libraries. The performance of the ML models was evaluated with R2 values and the root mean square error. Hardness values of 0.99 and 2.88, friability values of 0.92 and 0.02, and disintegration time values of 0.97 and 10.09 using the GBM algorithm gave the best results. CONCLUSIONS: In this study, we developed a computational approach to estimate the optimal pharmaceutical formulation of dexketoprofen. The results were evaluated by an expert, and it was found that they complied with Food and Drug Administration criteria.

A Solid Ultra Fine Self-Nanoemulsifying Drug Delivery System (S-SNEDDS) of Deferasirox for Improved Solubility: Optimization, Characterization, and In Vitro Cytotoxicity Studies.

The research work was designed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of deferasirox (DFX). According to the solubility studies of DFX in different components, Peceol, Kolliphor EL, and Transcutol were selected as excipients. Pseudo-ternary phase diagrams were constructed, and then SNEDDS formation assessment studies and solubility of DFX in selected SNEDDSs formulations were performed. DFX loaded SNEDDS were prepared and characterized. The optimum DFX-SNEDDS formulations were developed. The relative safety of the optimized SNEDDS formulation was examined in a human immortalized myelogenous leukemia cell line, K562 cells, using the MTT cell viability test. Cytotoxicity studies revealed more cell viability (71.44%) of DFX loaded SNEDDS compared to pure DFX (3.99%) at 40 µM. The selected DFX-SNEDDS formulation was converted into S-SNEDDS by adsorbing into porous carriers, in order to study its dissolution behavior. The in vitro drug release studies indicated that DFX release (Q5%) from S-SNEDDS solidified with Neusilin UFL2 was significantly higher (93.6 ± 0.7% within 5 min) compared with the marketed product (81.65 ± 2.10%). The overall results indicated that the S-SNEDDS formulation of DFX could have the potential to enhance the solubility of DFX, which would in turn have the potential to improve its oral bioavailability as a safe novel delivery system.

In Vitro Skin Permeation and Antifungal Activity of Naftifine Microemulsions.

OBJECTIVES: Microemulsions are fluid, isotropic, colloidal systems that have been widely studied as drug delivery systems. The percutaneous transport of active agents can be enhanced by their microemulsion formulation when compared to conventional formulations. The purpose of this study was to evaluate naftifine-loaded microemulsions with the objective of improving the skin permeation of the drug. MATERIALS AND METHODS: Microemulsions comprising oleic acid (oil phase), Kolliphor EL or Kolliphor RH40 (surfactant), Transcutol (co-surfactant), and water were prepared and physicochemical characterization was performed. In vitro skin permeation of naftifine from microemulsions was investigated and compared with that of its conventional commercial formulation. Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to evaluate the interaction between the microemulsions and the stratum corneum lipids. Candida albicans American Type Culture Collection (ATCC) 10231 and Candida parapsilosis were used to evaluate the antifungal susceptibility of the naftifine-loaded microemulsions. RESULTS: The microemulsion formulation containing Kolliphor RH40 as co-surfactant increased naftifine permeation through pig skin significantly when compared with the commercial topical formulation (p<0.05). ATR-FTIR spectroscopy showed that microemulsions increased the fluidity of the stratum corneum lipid bilayers. Drug-loaded microemulsions possessed superior antifungal activity against Candida albicans ATCC 10231 and Candida parapsilosis. CONCLUSION: This study demonstrated that microemulsions could be suggested as an alternative topical carrier with potential for enhanced skin delivery of naftifine.

Micelles: Promising Ocular Drug Carriers for Anterior and Posterior Segment Diseases.

Micelles have been studied in the targeting of drug substances to different tissues as a nano-sized delivery system for many years. Sustained drug release, ease of production, increased solubility, and bioavailability of drugs with low water solubility are the most important superiorites of micellar carriers. These advantages paved the way for the use of micelles as a drug delivery system in the ocular tissues. The unique anatomical structure of the eye as well as its natural barriers and physiology affect ocular bioavailability of the drugs negatively. Conventional dosage forms can only reach the anterior segment of the eye and are used for the treatment of diseases of this segment. In the treatment of posterior segment diseases, conventional dosage forms are administered sclerally, via an intravitreal injection, or systemically. However, ocular irritation, low patient compliance, and high side effects are also observed. Micellar ocular drug delivery systems have significant promise for the treatment of ocular diseases. The potential of micellar systems ocular drug delivery has been demonstrated by in vivo animal experiments and clinical studies, and they are continuing extensively. In this review, the recent research studies, in which the positive outcomes of micelles for ocular targeting of drugs for both anterior and posterior segment diseases as well as glaucoma has been demonstrated by in vitro, ex vivo, or in vivo studies, are highlighted.

Optimization and Characterization of Aqueous Micellar Formulations for Ocular Delivery of an Antifungal Drug, Posaconazole.

BACKGROUND: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. OBJECTIVE: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. METHODS: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. RESULTS: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. CONCLUSION: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.