Search Results (105)

Background/objectives: The efficacy and safety of the XEN45 gel stent implant in patients with glaucoma have been amply demonstrated. XEN63 is a new device that has been developed with a larger bore. This multicenter, observational, retrospective study assessed the efficacy and safety of XEN63 in patients with glaucoma. Methods: Medical records from six participating centers were screened to identify patients meeting the inclusion criteria. The primary outcome was mean IOP at 6 months after surgery. Results: The study included 114 eyes from 102 patients (XEN63 alone: 68 eyes, and XEN63 + Phaco: 46 eyes); 92% of patients had primary open-angle glaucoma. Baseline IOP for all patients was a median of 23.0 mmHg (IQR: 18.5–27.5 mmHg), which decreased significantly on day one post-surgery to 7.0 mmHg (IQR: 4.5–9.5 mmHg) and gradually stabilized at around 13.5 mmHg (IQR: 10.5–16.5 mmHg) by 6 months with no significant differences between groups at 6 months. The number of ocular hypertensive medications (OHMs) reduced significantly from a baseline median of 2.7 ± 1.1 to 0.5 ± 1.0 at 6 months in the entire cohort. The XEN63 alone group showed a significantly lower need for OHMs at 3 and 6 months. The surgical success rate was comparable between the two groups (54.4% vs. 47.8%, p = 0.05, XEN63 alone and XEN63 + Phaco). There was no statistically significant difference in survival outcomes between the XEN63 (0.59, 95% CI: 0.49–0.73) and XEN63 + Phaco groups (0.55, 95% CI: 0.42–0.72) (p = 0.89). Conclusions: In the largest study with XEN63 to date, the device appears to significantly decrease the IOP and the OHMs. Simultaneous XEN63 implant and phacoemulsification showed similar outcomes compared to XEN63 alone. Full article

Nanoemulsions (NEs) have emerged as effective drug delivery systems over the past few decades due to their multifaceted nature, offering advantages such as enhanced bioavailability, protection of encapsulated compounds, and low toxicity. In the present review, we focus on advancements in drug delivery over the last five years across (trans)dermal, oral, ocular, nasal, and intra-articular administration routes using NEs. Rational selection of components, surface functionalization, incorporation of permeation enhancers, and functionalization with targeting moieties are explored for each route discussed. Additionally, apart from NEs, we explore NE-based drug delivery systems (e.g., NE-based gels) while highlighting emerging approaches such as vaccination and theranostic applications. The growing interest in NEs for drug delivery purposes is reflected in clinical trials, which are also discussed. By summarizing the latest advances, exploring new strategies, and identifying critical challenges, this review focuses on developments for efficient NE-based therapeutic approaches. Full article

Purpose: To fabricate 3D-printed, biodegradable conjunctival gelatin methacrylate (GelMA) inserts that can release polyvinyl alcohol (PVA) when exposed to an ocular surface enzyme. Method: In this work, biodegradable conjunctival inserts were 3D-printed using a stereolithography-based technique. The release of PVA from these insert formulations (containing 10% GelMA and 5% PVA (P-Gel-5%)) was assessed along with different mathematical models of drug release. The biodegradation rates of these inserts were studied in the presence of a tear-film enzyme (matrix metalloproteinase-9; MMP9). The morphology of the inserts before and after enzymatic degradation was monitored using scanning electron microscopy. Results: The 3D-printed P-Gel-5% inserts formed a semi-interpenetrating network, which was mechanically stronger than GelMA inserts. The PVA release graphs demonstrate that at the end of 24 h, 222.7 ± 20.3 µg, 265.5 ± 27.1 µg, and 242.7 ± 30.4 µg of PVA were released when exposed to 25, 50, and 100 µg/mL of MMP9, respectively. The release profiles of the P-Gel-5% containing hydrogels in the presence of different concentrations of MMP9 showed the highest linearity with the Korsmeyer–Peppas model. The results suggest that the degradation rate over 24 h is a function of MMP9 enzyme concentration. Over 80% of P-Gel-5% inserts were degraded at the end of 8 h, 12 h, and 24 h in the presence of 100, 50, and 25 µg/mL MMP9 enzyme solutions, respectively. Conclusions: These results demonstrate the potential for 3D printing of GelMA for use as conjunctival inserts. These inserts could be used to deliver PVA, which is a well-known therapeutic agent for dry eye disease. PVA release is influenced by multiple mechanisms, including diffusion and enzymatic degradation, which is supported by morphological studies and biodegradation results. Full article

The topical administration of in situ hydrogels for ocular pathologies is a promising application strategy for providing high effectiveness and patient compliance. Curcumin, a natural polyphenol, possesses all the prerequisites for successful therapy of ophthalmic diseases, but unfortunately its physicochemical properties hurdle the practical use. Applying a composite in situ thermoresponsive hydrogel formulation embedded with polymer nanoparticles is a potent strategy to overcome all the identified drawbacks. In the present work we prepared uniform spherical nanoparticles (296.4 ± 3.1 nm) efficiently loaded with curcumin (EE% 82.5 ± 2.3%) based on the biocompatible and biodegradable poly-(lactic-co-glycolic acid). They were thoroughly physicochemically characterized in terms of FTIR, SEM, TGA, and DLS, in vitro release following Fickian diffusion (45.62 ± 2.37%), and stability over 6 months. Their lack of cytotoxicity was demonstrated in vitro on HaCaT cell lines, and the potential for antioxidant protection was also outlined, starting from concentrations as low as 0.1 µM and reaching 41% protection at 5 µM. An in situ thermoresponsive hydrogel (17% w/v poloxamer 407 and 0.1% Carbopol) with suitable properties for ophthalmic application was optimized with respect to gelation temperature (31.40 ± 0.36 °C), gelling time (8.99 ± 0.28 s) upon tears dilution, and gel erosion (90.75 ± 4.06%). Upon curcumin-loaded nanoparticle embedding, the in situ hydrogels demonstrated appropriate pseudoplastic behavior and viscosity at 35 °C (2129 ± 24 Pa∙s), 6-fold increase in the permeation, and prolonged release over 6 h. Full article

Ocular diseases affecting the anterior and posterior segments of the eye are major causes of global vision impairment. Curcumin, a natural polyphenol, exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties, making it a promising candidate for ocular therapy. However, its clinical use is hindered by low aqueous solubility, poor bioavailability, and rapid systemic elimination. This review comprehensively highlights advances in curcumin delivery systems aimed at overcoming these challenges. Emerging platforms, including proniosomal gels, transferosomes, and cyclodextrin complexes, have improved solubility, permeability, and ocular retention. Nanoparticle-based carriers, such as hybrid hydrogels and biodegradable nanoparticles, enable sustained release and targeted delivery, supporting treatments for posterior segment diseases like diabetic retinopathy and age-related macular degeneration. For anterior segment conditions, including keratitis and dry eye syndrome, cyclodextrin-based complexes and mucoadhesive systems enhance corneal permeability and drug retention. Mechanistically, curcumin modulates key pathways, such as NF-κB and TLR4, reducing oxidative stress, angiogenesis, and apoptosis. Emerging strategies like photodynamic therapy and neuroprotective approaches broaden their application to eyelid conditions and neuroinflammatory ocular diseases. These advancements address curcumin’s pharmacokinetic limitations, supporting its clinical translation into ophthalmic therapies. This work underscores curcumin’s potential in ocular disease management and advocates clinical trials to validate its safety, efficacy, and therapeutic relevance. Full article

Itraconazole (ITZ) is a potent antifungal agent. Its oral administration is associated with systemic toxicity, and its efficacy in ocular formulations is limited. This study aims to enhance ITZ’s ocular permeation and antifungal efficacy by loading it into deformable liposomes (DLs) based on Tween 80 (T) or Poloxamer 188 (P). Moreover, ITZ was loaded into biopolymer-coated DLs to augment its ocular availability. ITZ-loaded DLs were coated with hyaluronic acid (HA-DLs), chitosan (CS-DLs), or a layer-by-layer coating (CS/HA-DLs). These formulations were further laden into pH-sensitive in situ gels to provide a hybrid system to intensify their ocular adhesion properties. The prepared DLs were successfully prepared with vesicle sizes in nonorange (<200 nm). The zeta potential values of DLS were negative before coating and shifted to high negativity with HA coating and positivity with CS and CS/HA bilayer coating. These variations of zeta potential indicate successful CS and HA coatings. The optimized A high EE% was achieved with DLs-T: 89% (CS/HA-DLs-T), 86% (CS-DLs-T), 85% (HA-DLs-T), and 79% (HA-DLs-T). Therefore, DLs-T were incorporated into in situ gels, displaying optimal gelling capacity and viscosity. The release rate of ITZ from the coated DLs-laden in situ gels was slower than that observed with the uncoated DLs-gel. CS/HA-DLs-T laden-in situ gels showed the highest ex vivo transcorneal permeability and antifungal efficacy. These data suggest that the layer-by-layer-CS/HA-DLs-T presents a hopeful strategy for the ocular delivery of ITZ, offering a promising approach for managing ocular fungal infections. Full article

Fungal keratitis is a severe ocular infection caused by pathogenic fungi, leading to potential vision loss if untreated. Current antifungal treatments face limitations such as low solubility, poor corneal penetration, and limited therapeutic options. This study aimed to develop a thermosensitive in situ gel incorporating ketoconazole nanoparticles (NPs) to enhance drug solubility, stability, and antifungal activity. Ketoconazole NPs were prepared using the solvent displacement method, achieving a particle size of 198.25 ± 27.51 nm, encapsulation efficiency of 94.08 ± 0.51%, polydispersity index of 0.42 ± 0.08, and a positive zeta potential value of +10.08 ± 0.19 mV. The NPs exhibited sustained zero-order release kinetics. The optimized NPs were incorporated into a poloxamer-based in situ gel, demonstrating a gelation temperature of 34.67 ± 0.58 °C and the shortest gelation time. The formulation provided a 5-fold increase in solubility and a 10-fold improvement in drug release compared to pure ketoconazole. Stability studies confirmed the gel retained its physicochemical and rheological properties for three months under various storage conditions. The in situ gel showed sustained release, effective antifungal activity against Malassezia furfur, and good tolerability, suggesting it as a promising alternative for treating fungal keratitis with improved bioavailability and patient compliance. Full article

The study investigates the development and characterization of dual-loaded niosomes incorporated into ion-sensitive in situ gel as a potential drug delivery platform for ophthalmic application. Cannabidiol (CBD) and epigallocatechin-3-gallate (EGCG) simultaneously loaded niosomes were prepared via the thin film hydration (TFH) method followed by pulsatile sonication and were subjected to comprehensive physicochemical evaluation. The optimal composition was included in a gellan gum-based in situ gel, and the antimicrobial activity, in vitro toxicity in a suitable corneal epithelial model (HaCaT cell line), and antioxidant potential of the hybrid system were further assessed. Dual-loaded niosomes based on Span 60, Tween 60, and cholesterol (3.5:3.5:3 mol/mol) were characterized by appropriate size (250 nm), high entrapment efficiency values for both compounds (85% for CBD and 50% for EGCG) and sustained release profiles. The developed hybrid in situ gel exhibited suitable rheological characteristics to enhance the residence time on the ocular surface. The conducted microbiological studies reveal superior inhibition of methicillin-resistant Staphylococcus aureus (MRSA) adhesion by means of the niosomal in situ gel compared to the blank gel and untreated control. Regarding the antioxidant potential, the dual loading of CBD and EGCG in niosomes enhances their protective properties, and the inclusion of niosomes in gel form preserves these effects. The obtained outcomes indicate the developed niosomal in situ gel as a promising drug delivery platform in ophthalmology. Full article

In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance. Full article

Eye disorders affect a substantial portion of the global population, yet the availability of efficacious ophthalmic drug products remains limited. This can be partly ascribed to a number of factors: (1) inadequate understanding of physiological barriers, treatment strategies, drug and polymer properties, and delivery systems; (2) challenges in effectively delivering drugs to the anterior and posterior segments of the eye due to anatomical and physiological constraints; and (3) manufacturing and regulatory hurdles in ocular drug product development. The present review discusses innovative ocular delivery and treatments, encompassing implants, liposomes, nanoparticles, nanomicelles, microparticles, iontophoresis, in situ gels, contact lenses, microneedles, hydrogels, bispecific antibodies, and gene delivery strategies. Furthermore, this review also introduces advanced manufacturing technologies such as 3D printing and hot-melt extrusion (HME), aimed at improving bioavailability, reducing therapeutic dosages and side effects, facilitating the design of personalized ophthalmic dosage forms, as well as enhancing patient compliance. This comprehensive review lastly offers insights into digital healthcare, market trends, and industry and regulatory perspectives pertaining to ocular product development. Full article

Nebivolol hydrochloride (NEB), a 3rd-generation beta-blocker, was recently explored in managing open-angle glaucoma due to its mechanism of action involving nitric oxide release for the vasodilation. To overcome the issue of low ocular bioavailability and the systemic side effects associated with conventional ocular formulation (aqueous suspension), we designed and optimized polycaprolactone polymeric nanoparticles (NEB-PNPs) by applying design of experiments (DoE). The particle size and drug loading of the optimized NEB-PNPs were 270.9 ± 6.3 nm and 28.8 ± 2.4%, respectively. The optimized NEB-PNPs were suspended in a dual-sensitive in situ gel prepared using a mixture of P407 + P188 (as a thermo-sensitive polymer) and κCRG (as an ion-sensitive polymer), reported previously by our group. The NEB-PNPs-loaded in situ gel (NEB-PNPs-ISG) formulation was characterized for its rheological behavior, physical and chemical stability, in vitro drug release, and in vivo efficacy. The NEB-PNPs-loaded in situ gel, in ocular pharmacokinetic studies, achieved higher aqueous humor exposure (AUC_0–t = 329.2 ng × h/mL) and for longer duration (mean residence time = 9.7 h) than compared to the aqueous suspension of plain NEB (AUC_0–t = 189 ng × h/mL and mean residence time = 6.1 h) reported from our previous work. The pharmacokinetic performance of NEB-PNPs-loaded in situ gel translated into a pharmacodynamic response with 5-fold increase in the overall percent reduction in intraocular pressure by the formulation compared to the aqueous suspension of plain NEB reported from our previous work. Further, the mean response time of NEB-PNPs-loaded in situ gel (12.4 ± 0.6 h) was three times higher than aqueous suspension of plain NEB (4.06 ± 0.3 h). Full article

The primary source of hard fiber globally is Agave sisalana Perrine, also known as sisal. In areas where sisal is grown, the roots of the plant are usually left in the field after it has stopped producing, which leads to soil degradation and decreased sisal productivity. It is, therefore, critical to find alternatives to reuse this waste. This study explores the potential use of sisal waste in the cosmetic industry by incorporating a hydroethanolic extract (HER) into a cream–gel formulation, taking advantage of the plant’s recognized ethnopharmacological value. The study involves analyzing the extract’s phytochemical composition (flavonoids) and evaluating its cytotoxicity. Subsequently, the antioxidant and antiglycation activities of the extract and cream–gel are evaluated, as well as ex vivo ocular toxicity, photoprotective activity, and preliminary stability analyses. The HER extract showed a flavonoid composition (catechin, kaempferol, isorhamnetin, and chrysin) and maintained cell viability above 70% throughout all time points analyzed in the MTT assay. Furthermore, the extract and the formulation demonstrated proven antioxidant and antiglycation activities. The cream–gel’s UVB and UVA protection effectiveness with the HER was comparable to that of synthetic UVB/UVA sunscreens, with the samples proving nonirritating and stable. In conclusion, the extract has a significant presence of flavonoids, and the cream–gel developed with it did not present cytotoxicity and met the stability requirements, indicating phytocosmetic potential with antioxidant, antiglycation, and photoprotective properties. Full article

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs’ solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson–Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB. Full article

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye’s surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel–water interactions, indicating that HA affects the water–polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain. Full article

In situ poloxamer-based gels are increasingly being explored as ocular drug delivery carriers to extend the release of active substances, thereby enhancing bioavailability. The objective of this study was to develop thermally stable in situ gels incorporating balsam poplar bud extract, propolis extract, and p-coumaric acid solution and to evaluate the physicochemical parameters of these gelified eye drops. This research assessed the compatibility of poloxamer-based eye drops with active components, their physicochemical properties, stability post-sterilization and during storage, and the release profiles of the active compounds. Fifteen eye drop formulations were prepared and categorized into three groups based on active components. One of the active components was propolis extract. As an alternative to propolis, eye drops containing the plant precursor, balsam poplar bud extract, were developed. The third group’s active component was p-coumaric acid, a dominant phenolic acid in propolis and balsam poplar bud extracts. The study reported phenolic contents of 76.63 CAE mg/g for propolis and 83.25 CAE mg/g for balsam poplar bud aqueous extracts, with balsam poplar bud extracts showing higher SPF values (14.0) compared to propolis (12.7), while p-coumaric acid solution exhibited the highest SPF values (25.5). All eye drops were transparent, with pH values meeting the requirements for ocular drops. Formulations containing 8–10% poloxamer 407 met the criteria for in situ gels. All formulations remained stable for 90 days. Conclusion: The study results indicate that the formulated gels possess suitable physicochemical properties, are resistant to applied autoclaving conditions, and exhibit an extended release of active compounds with an increase in poloxamer content. Full article