Ocular Delivery Research Articles

Formulation And Evaluation Of Biodegradable Microsphere Hydrogel For Ocular Delivery Of Ofloxacin

The objective of the present investigation was to explore the hydrogel microspheres loaded with Ofloxacin to obtain controlled release for ocular delivery. The FTIR spectra of pure drug and the drug excipient mixture revealed no chemical interaction. Ofloxacin loaded hydrogel microspheres were prepared using Chitosan/Pluronic F127 blend and emulsion crosslinking method. F7 with blend ratio 3.33:1 exhibited the highest encapsulation efficiency (77.85%) whereas the lowest encapsulation was witnesses in the formulation F3 (32.10%) which has a blend ratio of 15:1. The particle size ranged from 29.3 µm for F3 to 146.5 µm for F7. The microspheres exhibited negative zeta potential and the value was found to be -17.5mV for F7. F3 exhibited the highest water uptake (316.0 %) whereas F7 exhibited the lowest water uptake (81.0 %). F7 released around 58.4% drug after 24 h. Hence F7 was considered to be the most optimized formulation. The release of Ofloxacin from F7 followed Higuchi mathematical model suggesting Non-Fickian diffusion.

Safety and Efficacy of Adeno-Associated Viral Gene Therapy in Patients With Retinal Degeneration: A Systematic Review and Meta-Analysis.

This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1. Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%). AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up. This systematic review will help to inform and guide future clinical trials.

Preparation of polycaprolactone and polymethacrylate nanofibers for controlled ocular delivery of ketorolac tromethamine: Pharmacokinetic study in Rabbit's Eye

Ophthalmitis is an inflammation of the eye triggered by various conditions including diseases, allergy, trauma, or surgery. Management of this condition usually includes administration of topical anti-inflammatory eye drops such as nonsteroidal anti-inflammatory drugs. To overcome the challenges of conventional eye drops such as frequent administration and low intraocular bioavailability, nanofibrous inserts of Ketorolac tromethamine (KET) were developed in this study. Polycaprolactone and polymethacrylate containing KET were electrospun to prepare biocompatible and biodegradable nanofibers. The inserts were studied for morphology, drug-polymer interaction, physicochemical properties, cell viability, in vitro drug release study and pharmacokinetic study in rabbit's eye. Uniform nanofibers with mean diameters < 350 nm were developed. Suitable mechanical properties with tensile strength up to 2.8 MPa indicated high strength and flexibility of inserts. Nanofibers exhibited controlled drug release for up to 140 h at a concentration more than 50 μg/ml in tears without causing any damage or irritation to the eye. Formulations indicated enhanced pharmacokinetics with 6- to 8-times higher Area Under the Curve (AUC0–144) compared to KET eye drop. Acceptable cell viability confirmed the safety of inserts. Due to the fact that this preservative-free polymer insert can obtain therapeutic concentration in the tear film without fluctuation, it can be a suitable alternative for the treatment of intraocular inflammations with less complications, easier use, and even higher intraocular penetration.

Ocular Mucoadhesive and Biodegradable Sponge-Like Inserts for the Sustained and Controlled Delivery of Voriconazole; Preparation, D-optimal Factorial Optimization and in-vivo Evaluation

The aim of this study was to formulate and optimize by statistical means mucoadhesive and biodegradable sponge-like inserts loaded with voriconazole (VCZ) which increases the contact time of the drug with the eye and sustain its release from the formula in a controlled manner. This avoids the pulsed effect reported for the drug suspension and results in reducing the number of drug instillations in the eye with the result of enhancing the patient compliance. Also, the sponge like nature of the insert reduces the foreign body sensation caused by other ocular solid dosage forms. They were prepared using casting/freeze-drying technique using five polymers namely high molecular weight chitosan (CH), sodium alginate (AL), sodium carboxy methyl cellulose (CMC), gellan gum (GG) and xanthan gum (XG). The prepared inserts were subjected to evaluations of their visual appearance, weight variation, drug content, surface pH, in-vitro release (percent drug released after 1h (Q1 (%)), mean dissolution time (MDT) and dissolution efficiency (DE)) in addition to kinetic analysis of the release data, water uptake, mucoadhesion and rheology of the forming plain polymer solution at the maximum rate of shear. The independent variables of the D-optimal factorial design were the polymer type and concentration while Q1 (%), MDT, DE, % water uptake after 15 minutes and rheology at the maximum rate of shear were chosen as dependant variables. The performed optimization process using design expert software showed an optimum formula consisting of 2 % GG. It showed slow release behavior compared to the drug suspension. FTIR and DSC studies showed that there is no interaction between VCZ and GG. The optimum formula has good in-vitro mucoadhesive properties and pH in the safe ocular range. Moreover, it showed promising in-vivo results of rapid hydration and gelling in addition to good mucoadhesive behavior when instilled in the eye, high ocular safety and biocompatibility, sustained antifungal activity in comparison to the drug suspension and finally biodegradation. So, it may be taken into consideration as an outstanding carrier for the ocular delivery of VCZ.

Ophthalmic Bimatoprost-Loaded Niosomal In Situ Gel: Preparation, Optimization, and In Vivo Pharmacodynamics Study.

This study aimed at formulating the antiglaucoma agent, Bimatoprost (BMT), into niosomal in situ gel (BMT-ISG) for ocular delivery. Niosomes containing cholesterol/span 60 entrapping BMT were fabricated using a thin-film hydration method. The fabricated niosomes were optimized and characterized for entrapment efficiency (%EE) and size. The optimized BMT-loaded niosomal formulation prepared at a cholesterol/span 60 ratio of 1:2 exhibited the highest entrapment (81.2 ± 1.2%) and a small particle size (167.3 ± 9.1 nm), and they were selected for incorporation into in situ gelling systems (BMT-ISGs) based on Pluronic F127/Pluronic F68. Finally, the in vivo efficiency of the BMT-ISG formulation, in terms of lowering the intraocular pressure (IOP) in normotensive male albino rabbits following ocular administration, was assessed and compared to that of BMT ophthalmic solution. All the formulated BMT-ISGs showed sol-gel transition temperatures ranging from 28.1 °C to 40.5 ± 1.6 °C. In addition, the BMT-ISG formulation sustained in vitro BMT release for up to 24 h. Interestingly, in vivo experiments depicted that topical ocular administration of optimized BMT-ISG formulation elicited a significant decline in IOP, with maximum mean decreases in IOP of 9.7 ± 0.6 mm Hg, compared to BMT aqueous solution (5.8 ± 0.6 mm Hg). Most importantly, no signs of irritation to the rabbit's eye were observed following topical ocular administration of the optimized BMT-ISG formulation. Collectively, our results suggested that niosomal in situ gels might be a feasible delivery vehicle for topical ocular administration of anti-glaucoma agents, particularly those with poor ocular bioavailability.

Advances in Therapeutic Contact Lenses for the Management of Different Ocular Conditions.

In the advent of an increasingly aging population and due to the popularity of electronic devices, ocular conditions have become more prevalent. In the world of medicine, accomplishing eye medication administration has always been a difficult task. Despite the fact that there are many commercial eye drops, most of them have important limitations, due to quick clearance mechanisms and ocular barrers. One solution with tremendous potential is the contact lens used as a medication delivery vehicle to bypass this constraint. Therapeutic contact lenses for ocular medication delivery have attracted a lot of attention because they have the potential to improve ocular bioavailability and patient compliance, both with minimal side effects. However, it is essential not to compromise essential features such as water content, optical transparency, and modulus to attain positive in vitro and in vivo outcomes with respect to a sustained drug delivery profile from impregnated contact lenses. Aside from difficulties like drug stability and burst release, the changing of lens physico-chemical features caused by therapeutic or non-therapeutic components can limit the commercialization potential of pharmaceutical-loaded lenses. Research has progressed towards bioinspired techniques and smart materials, to improve the efficacy of drug-eluting contact lenses. The bioinspired method uses polymeric materials, and a specialized molecule-recognition technique called molecular imprinting or a stimuli-responsive system to improve biocompatibility and support the drug delivery efficacy of drug-eluting contact lenses. This review encompasses strategies of material design, lens manufacturing and drug impregnation under the current auspices of ophthalmic therapies and projects an outlook onto future opportunities in the field of eye condition management by means of an active principle-eluting contact lens.

In situ forming hydrogel loaded with predatory bacteria treats drug-resistant corneal infection

The development of potent bactericidal antibiotic alternatives is important to address the current antibiotic crisis. A representative example is the topical delivery of predatory Bdellovibrio bacteriovorus bacteria to treat ocular bacterial infection. However, the direct topical use of B. bacteriovorus suspensions has the problem of easy loss and inactivation. Here, a B. bacteriovorus in situ forming hydrogel (BIG) was constructed for the ocular delivery of B. bacteriovorus. BIGs, as a fluid in their primitive state, were temperature- and cation- dually sensitive, which was rapidly transformed into immobile gels in the ocular environment. BIGs not only kept the activity of B. bacteriovorus but also retained on the ocular surface for a long time. The biosafety of BIGs was good without HCEC cell toxicity and hemolysis. More importantly, BIGs highly inhibited the growth of drug-resistant Pseudomonas aeruginosa whether in vitro or in the infected rat eyes. The ocular infection was completely controlled by BIGs with no corneal ulcers and inflammations. This living bacteria gel is a promising medication for the local treatment of drug-resistant bacteria-induced ocular infection.

Preparation and characteristics of a thermosensitive in situ gel loaded with chitosan nanoparticles for optimal ocular delivery of chloramphenicol

Preparation and characteristics of a thermosensitive in situ gel loaded with chitosan nanoparticles for optimal ocular delivery of chloramphenicol

Fenofibrate loaded nanofibers based thermo-responsive gel for ocular delivery: Formulation development, characterization and in vitro toxicity study

Fenofibrate loaded nanofibers based thermo-responsive gel for ocular delivery: Formulation development, characterization and in vitro toxicity study

Design and Optimization of Ganciclovir Nanosuspension Loaded In Situ Gelling Mucoadhesive Eye Drops for Herpetic Keratitis

Ganciclovir (GCR), an antiviral drug used to treat herpetic keratitis, is less effective because of its poor bioavailability (BCS III). Nanosuspension (NS) is a promising technique for improving solubility and the dissolution of poorly soluble drugs by size reduction. Topical solution or conventional eye drop represents the easiest route to deliver drugs to the anterior eye segment; however, low precorneal retention, high nasolacrimal drainage, and metabolic degradation lead to low bioavailability. To overcome these limitations, incorporating GCR-NS into mucoadhesive in situ gel-forming (ISG) could enhance its ocular permeability and drug bioavailability. Therefore, this study aimed to design and optimize GCR-NS-loaded in situ gelling mucoadhesive eye drops (GCR-NS-loaded mucoadhesive ISG) for improving ophthalmic delivery. Pluronic® F127 (P127), an ophthalmic gel forming, was selected as a polymer due to self-gelling formation by temperature-triggered in situ gelling at ocular temperature. Moreover, hyaluronic acid-modified catechol (HA-cat), a novel mucoadhesive polymer, was combined to achieve the desired ocular mucoadhesion and facilitate ophthalmic delivery. Optimized GCR-NS formulation prepared using the nanoprecipitation technique was selected based on the central composite design (CCD) model by evaluating their particle size, polydispersity index (PDI), and zeta potential, before being loaded into mucoadhesive ISG. The optimal GCR-NS-loaded mucoadhesive ISG (F7) revealed the desired physicochemical properties with better viscosity, mucoadhesion, and gelling capacity at physiological conditions, high ocular permeation with a sustained manner over 24 h compared to eye drop suspension. Accordingly, GCR-NS-loaded mucoadhesive ISG could be a promising ocular delivery system for the effective local delivery of GCR for herpetic keratitis. Keywords: Ganciclovir, Nanosuspension, Mucoadhesive eye drop, Ophthalmic delivery, In situ gelling

THE CURRENT STATUS IN MUCOSAL DRUG DELIVERY SYSTEM (MDDS) AND FUTURE PROSPECTUS IN DELIVERY: A SYSTEMATIC REVIEW

This systematic review aims to provide a comprehensive overview of the current status of mucosal drug delivery systems (MDDS) and explore their future prospects in drug delivery. MDDS have gained significant attention in recent years due to their potential to enhance drug absorption, improve therapeutic efficacy, and minimize systemic side effects. This review critically evaluates the existing literature on MDDS, including various mucosal routes such as oral, nasal, ocular, pulmonary, and vaginal delivery. Additionally, it discusses the challenges associated with MDDS, such as formulation development, stability, and regulatory considerations. Furthermore, this review highlights emerging technologies and innovative strategies that hold promise for the future of MDDS. Overall, this systematic review provides valuable insights into the current landscape of MDDS and offers recommendations for future research and development in this field.

Development of innovative electrospun nepafenac-loaded nanofibers-based ophthalmic inserts

Electrospun nanofibers can be utilized to develop patient-centric ophthalmic formulations with reasonable bioavailability at the targeted site. The current study aimed to develop 0.1 % w/w of nepafenac-loaded electrospun nanofibrous webs as potential candidates for ocular delivery of nepafenac with improved solubility and stability. Nine different formulations were prepared by electrospinning and investigated for morphology, physicochemical properties, drug release, cytocompatibility, and in vitro and ex vivo permeability. The scanning electron microscopy images showed fibrous samples. Fourier transform infrared spectroscopy and X-ray diffraction confirmed the polymer cross-linking and the formation of amorphous solid dispersion. All formulations showed complete and fast release of nepafenac (≤60 min), and the release followed first-order kinetics (β values for all formulations were < 1). The formulations (F3, F6, and F9) showed considerable in vitro and ex vivo permeability. The Raman studies revealed comparable corneal distributions of F3 and the commercial Nevanac® suspension at 60 min (p value = 0.6433). The fibrous composition remains stable under stress conditions (40 ± 2 °C, 75 ± 5 % relative humidity). The formulation composition showed good cytocompatibility with hen eggs tested on the chorioallantoic membrane of chick embryos. The developed nanofiber webs could be a promising candidate for nepafenac-loaded ophthalmic inserts.

AAV-Based Strategies for Treatment of Retinal and Choroidal Vascular Diseases: Advances in Age-Related Macular Degeneration and Diabetic Retinopathy Therapies.

Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are vascular diseases with high prevalence, ranking among the leading causes of blindness and vision loss worldwide. Despite being effective, current treatments for AMD and DR are burdensome for patients and clinicians, resulting in suboptimal compliance and real risk of vision loss. Thus, there is an unmet need for long-lasting alternatives with improved safety and efficacy. Adeno-associated virus (AAV) is the leading vector for ocular gene delivery, given its ability to enable long-term expression while eliciting relatively mild immune responses. Progress has been made in AAV-based gene therapies for not only inherited retinal diseases but also acquired conditions with preclinical and clinical studies of AMD and DR showing promising results. These studies have explored several pathways involved in the disease pathogenesis, as well as different strategies to optimise gene delivery. These include engineered capsids with enhanced tropism to particular cell types, and expression cassettes incorporating elements for a targeted and controlled expression. Multiple-acting constructs have also been investigated, in addition to gene silencing and editing. Here, we provide an overview of strategies employing AAV-mediated gene delivery to treat AMD and DR. We discuss preclinical efficacy studies and present the latest data from clinical trials for both diseases.

Overview of Recent Advances in Nano-Based Ocular Drug Delivery.

Ocular diseases profoundly impact patients' vision and overall quality of life globally. However, effective ocular drug delivery presents formidable challenges within clinical pharmacology and biomaterial science, primarily due to the intricate anatomical and physiological barriers unique to the eye. In this comprehensive review, we aim to shed light on the anatomical and physiological features of the eye, emphasizing the natural barriers it presents to drug administration. Our goal is to provide a thorough overview of various characteristics inherent to each nano-based drug delivery system. These encompass nanomicelles, nanoparticles, nanosuspensions, nanoemulsions, microemulsions, nanofibers, dendrimers, liposomes, niosomes, nanowafers, contact lenses, hydrogels, microneedles, and innovative gene therapy approaches employing nano-based ocular delivery techniques. We delve into the biology and methodology of these systems, introducing their clinical applications over the past decade. Furthermore, we discuss the advantages and challenges illuminated by recent studies. While nano-based drug delivery systems for ophthalmic formulations are gaining increasing attention, further research is imperative to address potential safety and toxicity concerns.

Design, optimization and pharmacokinetic evaluation of PLGA phosphatidylcholine hybrid nanoparticles of triamcinolone acetonide loaded in situ gel for topical ocular delivery

Posterior uveitis (PU), which often has an autoimmune origin, can be treated effectively with synthetic glucocorticoid triamcinolone acetonide (TAA). Due to the limitations of topical TAA administration reaching the posterior segment of the eye, the drug is injected directly into the eye through an intravitreal injection. In this study, we prepared TAA loaded poly(lactic-co-glycolic acid) phosphatidylcholine hybrid nanoparticles (TAA-PLHNPs) using the principles of design of experiments (DoE) for topical ocular administration. The mean particle size (nm) and drug loading efficiency (LE%) for the optimized formulations were 163 ± 2.8 nm and 39 ± 1.9%, respectively. The TAA-PLHNPs were then loaded into the dual responsive in situ gel that we reported in our previous work. In vitro assessments were done to show that the formulations are safe for ocular administration. Finally, in vivo ocular pharmacokinetic studies were performed to compare pharmacokinetic parameters of TAA-PLHNPs and TAA-PLHNPs loaded in situ gel with each other and with the previously reported conventional formulation of TAA (aqueous suspension of TAA with 20% hydroxypropyl β-cyclodextrin (TAA-HP-β-CD-Susp)). TAA-PLHNPs loaded dual responsive in situ gel (TAA-PLHNP-ISG) achieved higher concentrations of TAA in the vitreous humor (Cmax of 946.53 ng/mL) and sustained (MRT0–∞ of 16.26 h) the drug concentrations for longer period of time compared to aqueous suspension of TAA-PLHNPs (TAA-PLHNP-Susp) and TAA-HP-β-CD-Susp.

Lipid nanoparticles with PEG-variant surface modifications mediate genome editing in the mouse retina

Ocular delivery of lipid nanoparticle (LNPs) packaged mRNA can enable efficient gene delivery and editing. We generated LNP variants through the inclusion of positively charged-amine-modified polyethylene glycol (PEG)-lipids (LNPa), negatively charged-carboxyl-(LNPz) and carboxy-ester (LNPx) modified PEG-lipids, and neutral unmodified PEG-lipids (LNP). Subretinal injections of LNPa containing Cre mRNA in the mouse show tdTomato signal in the retinal pigmented epithelium (RPE) like conventional LNPs. Unexpectedly, LNPx and LNPz show 27% and 16% photoreceptor transfection, respectively, with striking localization extending from the photoreceptor synaptic pedicle to the outer segments, displaying pan-retinal distribution in the photoreceptors and RPE. LNPx containing Cas9 mRNA and sgAi9 leads to the formation of an oval elongated structure with a neutral charge resulting in 16.4% editing restricted to RPE. Surface modifications of LNPs with PEG variants can alter cellular tropism of mRNA. LNPs enable genome editing in the retina and in the future can be used to correct genetic mutations that lead to blindness.

Exploring the potential of transethosomes in therapeutic delivery: A comprehensive review

AbstractThe growing need for innovative drug delivery systems has led to extensive research to address the limitations associated with conventional dosage forms. Lipid nanoparticles have become prominent as frontline nanocarriers for the delivery of drugs and vaccine formulations. However, the pursuit of new materials and modifications to improve lipid nanocarrier properties remains ongoing. In this context, transethosomes have gained attention as a promising solution, offering distinct advantages over traditional formulations. Transethosomes minimize plasma fluctuations, first‐pass metabolism, organ toxicity, and poor bioavailability. This comprehensive review provides an in‐depth exploration of transethosomes, starting with an overview of the impact of formulation components on their properties and effective targeting. This article delves into the production techniques and evaluation properties employed to ensure efficient drug delivery. A significant contribution of this review lies in the analysis of various routes of administration for transethosomes, including transdermal, transvaginal, pulmonary, and ocular delivery, showcasing the versatility of transethosome‐loaded with drugs and their potential to target specific tissues to achieve controlled release. Furthermore, the potential of functionalization and photodynamic therapy approaches to enhance drug delivery efficacy are explored. Overall, this review emphasizes the significant potentiality of transethosomes as a promising drug delivery system addressing the challenges associated with conventional drug delivery approaches.

NAD+-associated-hyaluronic acid and poly(L-lysine) polyelectrolyte complexes: An evaluation of their potential for ocular drug delivery

This study details the formation and characterisation of a novel nicotinamide adenine dinucleotide (NAD+)-associated polymeric nanoparticle system. The development of a polyelectrolyte complex (PEC) composed of two natural polyelectrolytes, hyaluronic acid and poly(L-lysine), and an evaluation of its suitability for NAD+ ocular delivery, primarily based on its physicochemical properties and in vitro release profile under physiological ocular flow rates, were of key focus. Following optimisation of formulation method conditions such as complexation pH, mode of addition, and charge ratio, the PEC was successfully formulated under mild formulation conditions via polyelectrolyte complexation. With a size of 235.1 ± 19.0 nm, a PDI value of 0.214 ± 0.140, and a zeta potential value of – 38.0 ± 1.1 mV, the chosen PEC, loaded with 430 µg of NAD+ per mg of PEC, exhibited non-Fickian, sustained release at physiological flowrates of 10.9 ± 0.2 mg of NAD+ over 14 h. PECs containing up to 200 µM of NAD+ did not induce any significant cytotoxic effects on an immortalised human corneal epithelial cell line. Using fluorescent labeling, the NAD+-associated PECs demonstrated retention within the corneal epithelium layer of a porcine model up to 6 h post incubation under physiological conditions. A study of the physicochemical behaviour of the PECs, in terms of size, zeta potential and NAD+ complexation in response to environmental stimuli,highlighted the dynamic nature of the PEC matrix and its dependence on both pH and ionic condition. Considering the successful formation of reproducible NAD+-associated PECs with suitable characteristics for ocular drug delivery via an inexpensive formulation method, they provide a promising platform for NAD+ ocular delivery with a strong potential to improve ocular health.

Flexosomes as a promising nanoplatform for enhancing tolnaftate ocular delivery: Formulation, in vitro characterization, statistical optimization, ex vivo and microbial in vivo studies

The eye is a complex organ with a unique physiology and anatomy. Using novel nanosystems is expected to enhance ocular drug permeation and retention. Hence, this work aimed to study the potential of flexosomes as an ocular delivery system to enhance the corneal permeation and antifungal activity of Tolnaftate (TOL). Different flexosomes formulae were formulated using ethanol injection method, employing a 31.22 full factorial design. The studied formulation variables were: X1: amount of stearyl amine, X2: hydration volume and X3: type of edge activator. Encapsulation efficiency, particle size and zeta potential were selected as dependent variables. FX5 was selected as the optimal TOL flexosomes and showed encapsulation efficiency of 66.08 ± 11.38%, particle size of 154.99 ± 29.11 nm and zeta potential of 42.95 ± 0.64 mV. FX5 was subjected to further ex vivo and in vivo studies which showed that TOL flux was significantly increased through FX5 compared to TOL suspension. Draize test and histopatholoigal tests assured that FX5 is safe to be used for eye.. The in vivo fungal susceptibility testing using Aspergillus niger demonstrated the superior and more durable antifungal activity of FX5 than TOL suspension. Hence, FX5 can be considered as promising nanocarrier for safe and efficient ocular TOL delivery.

Hyperlipidemia and lipid-lowering therapy in diabetic retinopathy (DR): A bibliometric study and visualization analysis in 1993–2023

BackgroundDiabetic retinopathy (DR) is a common complication in diabetic patients. DR is also a neurodegenerative disease. Patients with hyperglycemia, hyperlipidemia, and hypertension are vulnerable to retinopathy development. While the roles of blood glucose and blood pressure in the development of retinopathy have been extensively studied, the relationship between body fat and DR pathogenesis and the impact of lipid-reducing drugs on DR has just emerged as a research hotspot in DR study. We aim to visualize the contributions and cooperation of reporters, organizations, and nations, in addition to the research hotspots and trends in DR-related lipid research from 1993 to 2023, by bibliometric analysis. MethodsWe extracted all publications about DR-related lipid research from 1993 to 2023 from the Web of Science Core Collection, and bibliometric features were studied using VOSviewer and the CiteSpace program. Results1402 documents were retrieved. The number of studies has risen consistently for three decades, from an average of 16.8/year in the 1990s to 28.8/year in the 2000s, 64.5/year in 2010s, and reached 112/year in 2020–2022, confirming they are hot research topic in the field. These reports were from 93 nations/regions, with the USA, China, Japan, Australia, and England taking the leading positions. Diabetes Research and Clinical Practice was the journal that published the most studies, and Diabetes Care was the most quoted. We identified 6979 authors, with Wong TY having the most papers and being the most commonly co-cited. The most popular keyword, according to our research, is diabetic retinopathy. Oxidative stress, diabetic macular edema (DME), lipid peroxidation, and other topics have often been investigated. ConclusionDR-related lipid research is conducted mainly in North America, Asia, Oceania, and Europe. Much study has centered on the relationship between lipid-lowering therapy and DR pathogenesis. These studies strongly support using lipid-reducing medications (fenofibrate, statins, and omega-3 PUFAs), combined with hyperglycemia and hypertension therapy, to prevent and treat DR. However, the impact of fenofibrate or statin on retinopathy is not correlated with their action on blood lipid profiles. Thus, more randomized clinical trials with primary endpoints related to DR in T1D or T2D are merited. In addition, the lipid biomarker for DR (lipid aldehydes, ALEs, and cholesterol crystals), the action of lipid-reducing medicines on retinopathy, the mechanism of lipid-lowering medications preventing or curing DR, and ocular delivery of lipid-lowering drugs to diabetic patients are predicted as the research focus in the future in the DR-related lipid research field.