Search Results (336)

Background: The release study is a standard tool for the development, evaluation, and control of dosage forms. In the case of traditional drug delivery systems, it is conducted in accordance with the established principles available in the European and American Pharmacopoeias or guidelines proposed by registration agencies. The problem is the study of modern carriers, not yet described in compendia, which require adjustments to traditionally used methods. Objectives: The present study focuses on developing an optimal method for testing the release of cyclosporine (Cs, 0.5–4%) incorporated in solid lipid microparticles (SLM) dispersions (10%) intended for administration in the form of eye drops. This is a multicompartment lipid carrier that provides prolonged release of the active substance. Methods: Three methods of testing the release were compared: the dialysis bag method, the horizontal cells technique, and a method without a membrane. Results: During the analyses, the proper membrane was selected and the effect of the lysozyme enzyme on the release profile was analyzed. The effect of the composition of the acceptor fluid on the obtained results was also assessed. In the model without a membrane, up to 60% of the Cs was released within 30 min due to the burst effect. In horizontal chambers, no formulation released more than 14% of the Cs over 96 h, while at the same time, 60–70% of the Cs was released from the dialysis bag. Conclusions: Based on the obtained results, the dialysis bag method was selected to study the release of Cs from SLM without the need to use multicomponent artificial tear fluid as an acceptor medium. Full article

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Microneedle arrays (MNAs) are becoming increasingly popular due to their ease of use and effectiveness in drug delivery and diagnostic applications. Improvements in three-dimensional (3D) printing techniques have made it possible to fabricate MNAs with high precision, intricate designs, and customizable properties, expanding their potential in medical applications. While most studies have focused on transdermal applications, non-transdermal uses remain relatively underexplored. This review summarizes recent developments in 3D-printed MNAs intended for non-transdermal drug delivery and diagnostic purposes. It includes a literature review of studies published in the past ten years, organized by the target delivery site—such as the brain and central nervous system (CNS), oral cavity, eyes, gastrointestinal (GI) tract, and cardiovascular and reproductive systems, among other emerging areas. The findings show that 3D-printed MNAs are more adaptable than skin-based delivery, opening up exciting new possibilities for use in a variety of organs and systems. To guarantee the effective incorporation of polymeric non-transdermal MNAs into clinical practice, additional research is necessary to address current issues with materials, manufacturing processes, and regulatory approval. Full article

Sjögren’s syndrome (SS) is a chronic autoimmune disease primarily affecting the lacrimal and salivary glands, characterized by ocular and oral dryness. Beyond exocrine dysfunction, SS may also involve multiple organs and systems, contributing to systemic complications that impair a patient’s quality of life. Among these, ocular inflammation represents a significant clinical challenge, manifesting as dry eye disease and other vision-affecting complexities. Despite advances in SS understanding, the inflammatory mechanisms driving ocular manifestations remain incompletely elucidated. This review aims to clarify the key inflammatory pathways underlying ocular complications in SS and the clinical implications. Additionally, it discusses both conventional and novel therapeutic strategies focusing on mitigating SS-associated ocular inflammation, including targeted immunomodulatory agents, regenerative medicine, and innovative drug delivery systems. By integrating current knowledge from recent studies, this review attempts to provide researchers and clinicians with a comprehensive resource for optimizing SS treatment approaches. The advancement of targeted therapies and emerging mitigation strategies holds promise for improving patient outcomes and enhancing SS management. Full article

Retinal diseases can result in blindness and visual impairment. They represent a significant medical burden and adversely affect life expectancy. Recently, antibody- and nucleic acid-based pharmaceuticals have increasingly been used to treat retinal diseases, with improvement or cure as the goal; however, these drugs are currently only administered by intravitreal injection. In this study, we present a novel approach to treating retinal diseases using eye drops that contain PnkRNA, a single-stranded RNA nucleic acid. PnkRNA-loaded liposomes were shown to effectively deliver retinal drugs and significantly inhibit retinal thickening in a mouse retinal-vein occlusion model. Cationic modification of the liposome surface enhanced the delivery of nucleic acids and therapeutic efficacy. Moreover, to reduce the frequency of eye-drop administration, liposomes were incorporated into the thermoresponsive gels. This formulation provided sustained retinal delivery and exhibited superior therapeutic efficacy compared with liposomal eye drops. This nucleic acid retinal delivery technology represents a significant advancement in drug-delivery technology, offering a safe and simple treatment for retinal diseases. Full article

Cataracts, characterized by the opacification of the eye lens, remain a leading cause of reversible blindness globally. Age and diabetes are key risk factors, and with the increasing aging and diabetic population, the global burden of cataracts is projected to rise significantly. Current treatment is predominantly surgical; however, pharmacological strategies could offer a non-invasive alternative with the potential to delay, prevent, or even reverse cataract progression. Recent research has enhanced our understanding of cataractogenesis, emphasizing oxidative stress as a key underlying mechanism, but also including other processes such as calcium dysregulation and altered lens homeostasis or specific events induced by hyperglycemia in diabetic cataracts. New therapeutic approaches have emerged considering the molecular mechanisms involved in cataracts, most of which focus on pharmacological agents with antioxidant properties. Additionally, small-molecule chaperones, aldose reductase inhibitors, and protein aggregation inhibitors have also demonstrated potential in stabilizing or restoring lens protein structure and transparency. While experimental results have shown encouraging results, further research is needed to optimize drug delivery systems to the lens, assess long-term safety, and confirm the clinical efficacy of these treatments. This article reviews current progress in pharmacological treatments for cataracts, outlining challenges and prospects for future integration into clinical practice. Full article

Ocular diseases including glaucoma, diabetic retinopathy and age-related macular degeneration represent a growing global health burden, with current treatments often providing only symptomatic relief. Through an integrated approach combining preclinical models, molecular biology, and clinical insights, this review synthesizes 25 years of my translational research to advance therapeutic strategies for these conditions. Key findings demonstrate the following: (1) the dual neuroprotective and intraocular pressure-lowering effects of natural compounds (EGCG, forskolin) in glaucoma models; (2) successful development of Uparant, a first-in-class peptide inhibitor of pathological angiogenesis with efficacy in retinal disease models; and (3) innovative drug delivery systems (melatonin nanomicelles, liposomal sprays) that enhance ocular bioavailability. Notably, some of these approaches have progressed to early-phase clinical trials, demonstrating translational potential. Significant challenges remain in optimizing sustained drug delivery and addressing the heterogeneity of ocular diseases through personalized approaches. Future directions include combinatorial therapies and the application of artificial intelligence for treatment optimization. Collectively, this work establishes a framework for developing multi-target therapies that address both the molecular mechanisms and clinical needs in ophthalmology. Full article

Ocular drug delivery presents a persistent clinical challenge due to the protective anatomical structure of the eye, physiological barriers such as reflex blinking, and continuous tear fluid turnover. These factors significantly limit the bioavailability of topically applied medications, reducing the therapeutic effectiveness of conventional formulations, such as eye drops, ointments, and suspensions, particularly in the management of chronic ocular disorders, including dry eye syndrome, diabetic retinopathy, and age-related macular degeneration. Drug-eluting contact lenses (DECLs) offer a promising alternative, enabling sustained, localized, and controlled drug release directly at the ocular surface. While several reviews have addressed contact lenses as drug delivery platforms, this work provides a distinct perspective by focusing specifically on biodegradable polymer-based systems. Emphasis is placed on recent advances in the design and fabrication of DECLs using natural and synthetic biodegradable polymers, which offer superior biocompatibility, customizable degradation kinetics, and the capacity for programmable drug release. This review discusses the selection criteria for polymer matrices, strategies for drug incorporation, and key factors influencing release profiles. Moreover, this study highlights innovative methodologies and therapeutic approaches that differentiate it from the existing literature, providing a timely and comprehensive resource for researchers developing next-generation polymeric ocular drug delivery systems. Full article

Background/Objectives: The management of ocular tumours is faced with the challenge of developing a suitable treatment strategy with consideration of the anatomical and physiological protective barriers of the eye. Interferon alpha has been employed to treat patients with ocular tumours for decades; however, its short half-life and poor tolerability necessitate frequent administration. This study focuses on the design of an injectable pH-responsive and protective nanoparticle system dispersed into a thermo-responsive hydrogel for site-specific sustained delivery of interferon alpha (IFN-α2b) in the treatment of ocular surface tumours. Methods: The synthesis of a poly(ethylene glycol)-poly(caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG) triblock copolymer (PECE) was undertaken. The IFN-α2b was encapsulated in poly(β-amino ester) (PBAE) nanoparticles (NP) with pH-responsive characteristics to proposedly release the IFNα-2b in response to the acidic nature of the tumour microenvironment. This was followed by characterisation via Fourier transform infrared spectroscopy (FT-IR), ¹H-nuclear magnetic resonance (¹H-NMR) analysis, differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) analysis, thermogravimetric analysis (TGA), and thermal-transition analysis of the PECE hydrogels. Results: Release studies demonstrated that the PBAE nanoparticulate PEG-PCL-PEG hydrogel was both pH-responsive, while providing controlled release of IFN-α2b, and thermo-responsive. Release analysis highlighted that IFN-α2b-loaded NP dispersed into the hydrogel (IFNH) further prolonged the release of IFN-α2b with a pH-responsive yet controlled release rate in an acidic environment simulating a tumour microenvironment. The developed system proved to be biocompatible with human retinal pigment epithelial cells and the released IFN-α demonstrated bioactivity in the presence of an A172 glioblastoma cell line. Conclusions: In conclusion, the PECE hydrogel has promising potential for application as an ocular drug delivery system for the treatment of ocular tumours and could potentially overcome and prevent the drawbacks associated with the commercially available IFN-α2b injection. Full article

Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm², 5.446 ± 0.390 μg/cm²) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article

Background: Sjögren’s syndrome (SS) is a systemic autoimmune condition marked by significant dry eye disease (DED), leading to considerable corneal changes. These modifications, encompassing punctate epithelial erosions, chronic epithelial abnormalities, and corneal ulcers, significantly impact eyesight and quality of life. Progress in comprehending the corneal pathophysiology associated with SS has prompted innovative diagnostic and treatment approaches. Aim: This narrative review aims to examine developing trends in the pathogenesis, diagnostic methods, and treatment strategies for Sjögren’s syndrome-associated corneal changes. Methods: The study was based on a narrative review of the current literature available on PubMed and Cochrane from Jan 2000 to December 2024. Results: Corneal changes associated with Sjögren’s syndrome result from a multifactorial interaction of ocular surface inflammation, tear film instability, and epithelium degradation. Recent research underscores the significance of immune-mediated pathways, such as T-cell-induced inflammation and cytokine dysregulation, as crucial factors in corneal disease. Innovations in diagnostic instruments, including in vivo confocal microscopy and tear proteomics, provide earlier and more accurate identification of subclinical alterations in the corneal epithelium and stroma. Therapeutic developments concentrate on meeting the specific requirements of SS-related DED. Biological treatments, especially tailored inhibitors of interleukin-6 and tumor necrosis factor-alpha, show potential in mitigating inflammation and facilitating epithelial repair. Moreover, regenerative approaches, such as autologous serum tears and mesenchymal stem cell therapies, provide innovative methods to repair ocular surface integrity. Advanced drug delivery technologies, including nanoparticle-loaded eye drops, enhance bioavailability and therapeutic efficacy. Conclusion: Recent developments in comprehending SS-related corneal changes have transformed the management approach to precision medicine. The combination of improved diagnostics and innovative therapy approaches offers potential for reducing disease progression, maintaining corneal health, and enhancing patient outcomes. Subsequent investigations ought to concentrate on enhancing these tactics and examining their long-term safety and effectiveness. Clinicians and researchers must adopt these developments to successfully tackle the difficulties of SS-related corneal illness, providing hope for improved care and higher quality of life for those affected. Full article

Complex anatomical and physiological barriers make the eye a challenging organ to treat from a drug delivery perspective. Currently available treatment methods (topical eyedrops) for anterior segment diseases pose several limitations in terms of bioavailability and patient compliance. Conventional drug delivery methods to treat posterior segment ocular diseases are primarily intravitreal injection (IVT) of solutions. IVT is highly invasive and leads to retinal toxicity, endophthalmitis, and intraocular inflammation, frequently requiring professional administration and frequent clinical visits. Advanced drug delivery treatment strategies could improve patient compliance and convenience. Long-acting drug delivery platforms (biodegradable or nonbiodegradable) provide sustained/controlled release of drugs for at least four to six months. Smart drug delivery alternatives, for instance, in situ forming implants, are injectable formulations that form semisolid-to-solid implants in response to the various stimuli of pH, light, osmolarity, and temperature. Additionally, nanoparticulate drug delivery systems, contact lenses, electrospun patches, and microneedle-based drug delivery systems provide minimally invasive treatment options for ocular disorders. This comprehensive review focuses on advanced drug delivery options for the management of ocular disorders. Full article

Glaucoma, a primary cause of irreversible blindness, is most effectively managed by reducing intraocular pressure (IOP). Topical eye drops, which are conventional treatments, frequently encounter constraints regarding patient compliance, inconsistent dosage, and tolerability. Slow-release drug delivery systems have emerged as a promising innovation in response to these challenges. The objective of these systems is to enhance the efficacy of treatment and patient compliance by ensuring the consistent and sustained delivery of therapeutic agents over extended periods. Implantable devices, injectable formulations, and external applications are all categorized as slow-release therapies. By delivering medication directly to the target tissues in a controlled manner, these technologies have the potential to circumvent common issues associated with traditional regimens, such as forgotten doses or improper administration. These systems have been shown to obtain clinically meaningful reductions in IOP in studies, with some demonstrating efficacy that is comparable to that of established daily topical treatments. Despite their potential, slow-release therapies encounter obstacles that necessitate resolution. Potential complications during implantation or removal, long-term biocompatibility, and the cost of treatment are all areas of concern. Furthermore, further investigation is required to comprehensively assess their relative economic feasibility, patient acceptability, and long-term safety profiles in comparison to conventional treatments. This review summarizes the most recent findings in the scientific literature, underlining the role and possible limits of slow-release therapies in glaucoma with the aim of offering a comprehensive understanding of their potential clinical applications and challenges. This emphasizes the potential for these innovations to revolutionize care by addressing current knowledge gaps, while also emphasizing the areas in which further development and research are required. Full article

Retina, a light-sensitive layer of tissue of the eye, requires high levels of oxygen for its physiology. Retinal ischemia occurs due to inadequate supply of blood to the retina and choroid. Retinal ischemia is implicated in the development or progression of many ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). To date, anti-vascular endothelial growth factor (VEGF) treatment has been widely used to manage neovascular diseases associated with retinal ischemia. Nonetheless, a substantial number of patients with DR or AMD still suffer from incomplete response and adverse effects related to its therapy with limitations. Therefore, research scientists have been developing and finding novel treatments to protect against or prevent vision loss in those diseases. In this review article, we summarize the recent novel therapeutic approaches for the treatment of ischemic retinopathy (e.g., cell therapy, advanced molecular targeting, or drug delivery). This summary enables further research to obtain more solid evidence of novel effective drug development in retinal ischemic diseases. Full article

Background: The incorporation of polymers into drug delivery vehicles has been shown to be an effective strategy to prolong the residence time of active ingredients in the precorneal tear film and to increase ocular bioavailability. Objectives: The aim of this study was to develop novel, viscous eye drops containing olopatadine (OCH) as the active ingredient, polysaccharides hydroxypropyl guar gum (HPG), and sodium hyaluronate (SH), individually, and in combination as functional polymers. Methods: Viscous eye drops containing 0.1% OCH in combination with HPG (0.25%) and SH (0.4%), were prepared and evaluated for their physicochemical properties, rheological behavior, mucoadhesion, and preliminary stability. A novel rheological method was used to evaluate the resistance of the eye drops under simulated blinking conditions. In vivo efficacy was evaluated using an ocular itch test in mice to compare the formulations with a commercial product. Results: The formulations remained stable and transparent, with physicochemical parameters within acceptable ranges. Rheological studies confirmed pseudoplastic flow, with the HPG-SH combination exhibiting enhanced viscosity and shear-thinning properties for prolonged retention in the eye. Mucoadhesion was highest in SH-HPG formulations. During simulated blinking cycles, eye drops containing a combination of SH and HPG polymers fully regained their initial viscosity during the resting periods. Preliminary stability studies indicate that the formulated eye drops exhibit satisfactory physicochemical stability under various storage conditions. In vivo, OCH-SH and OCH-HPG-SH drops provided prolonged antipruritic and analgesic effects compared to the reference product. Conclusions: Polysaccharide-based innovative formulations improve OCH retention, enhancing therapeutic efficacy and patient compliance in the treatment of allergic conjunctivitis. Full article