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.

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.

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.

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.

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.

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.

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.

Preparation and in vitro/in vivo evaluation of cyclosporin A-loaded nanodecorated ocular implants for subconjunctival application.

In terms of ocular drug delivery, biodegradable implant systems have several advantages including the ability to provide constant drug concentration at the target site, no necessity for surgical removal, and minimum systemic side effects. Cyclosporin A (CsA) is a neutral, hydrophobic, cyclic peptide of amino acids that frequently used for dry eye disease treatment. The aim of this study was to develop a nanoparticle-loaded implant system for sustained-release CsA delivery following subconjunctival implantation. Poly(lactide-co-glycolide) (85:15) or poly-ε-caprolactone (PCL) were used to prepare two different nanoparticle formulations. These nanoparticles loaded into PCL or poly(lactide-co-caprolactone) implant formulations were prepared by two different methods, which were molding and electrospinning. Size and zeta potential of nanoparticles were determined and the morphology of the formulations were investigated by scanning electron microscopy. CsA-loading efficiencies were calculated and the in vitro degradation and in vitro release studies were performed. MTT test was also performed using L929 fibroblast cells to evaluate the cytotoxicity of the formulations. PCL-PCL-NP-I formulation was implanted to Swiss Albino mice with induced dry eye syndrome to evaluate the efficacy. In vitro release studies showed that the release from the formulations continues between 30 and 60 days, and the cell viability was found to be 77.4%-99.0%. In vivo studies showed that healing is significantly faster in the presence of the selected implant formulation. Results indicated that nanodecorated implants are promising ocular carriers for controlled-release CsA application.