Fungal Keratitis Research Articles

Bacterial and Fungal Keratitis in a Tertiary Care Hospital from Romania.

Infectious keratitis is a significant global problem that can lead to corneal blindness and visual impairments. This study aimed to investigate the etiology of infectious bacterial and fungal keratitis, identify the causative pathogens and their antimicrobial resistance patterns, and analyze the risk factors associated with the development of infectious keratitis. The study was observational and retrospective, involving 226 eyes from 223 patients presented at the Ophthalmology Clinic of the County Clinical Emergency Hospital of Craiova, Romania. The inclusion criteria included corneal ulceration/abscess/infiltrate present on slit-lamp examination and positive microbiological sampling for bacteria or fungi. The study found that the most common causes of infectious keratitis were coagulase-negative staphylococci (35.40%), Staphylococcus aureus (11.06%), and Pseudomonas aeruginosa (14.16%). The Gram-positive bacteria showed high resistance rates to penicillin, moderate rates to gentamycin and clindamycin, and low resistance to chinolones. The Gram-negative bacteria were highly resistant to ampicillin and amoxicillin-clavulanic acid, while third-generation cephalosporins, quinolones, and carbapenems were effective. Systemic antibiotics, such as vancomycine, piperacillin-tazobactam, amikacin, and ceftazidime, show promise against keratitis with low resistance rates, whereas carbapenems and topical aminoglycosides had higher resistance, leaving moxifloxacin as a potential topical option for Gram-positive bacteria and Pseudomonas aeruginosa, albeit with resistance concerns for Klebsiella spp. Although fungal keratitis was rare, Fusarium spp. and Candida albicans were the leading fungal pathogens, with incidences of 2.65% and 2.21%, respectively. Candida albicans was broadly susceptible to most antifungals, while Fusarium solani, Curvularia lunata, and Alternaria alternata exhibited resistance to many antifungals. Amphotericin B and caspofungin can be used as systemic antifungals in fungal keratitis. The study also identified risk factors for keratitis such as ocular trauma (65.92%, OR: 2.5), contact lens wear (11.94%, OR: 1.8), and corneal scarring/leukoma (10.17%, OR: 1.6). Keratitis was more frequent in individuals over 60 years old. The findings of this study have implications for the development of effective diagnostic, therapeutic, and preventive strategies for infectious keratitis.

Nanomicelles empower natamycin in treating fungal keratitis: An in vitro, ex vivo and in vivo study

Fungal infections of cornea are important causes of blindness especially in developing nations with tropical climate. However, the challenges associated with current treatments are responsible for poor outcome. Natamycin is the only FDA-approved antifungal drug to treat fungal keratitis, but unfortunately due to its poor water solubility, it is available as suspension. The marketed suspension (5% Natamycin) has rapid precorneal clearance, poor corneal permeability, a higher frequency of administration, and corneal irritation due to undissolved suspended drug particles. In our study, we developed clear and stable natamycin-loaded nanomicelles (1% Natcel) to overcome the above challenges. We demonstrated that 1% Natcel could permeate the cornea better than 5% suspension. The developed 1% Natcel was able to provide sustained release for up to 24 h. Further, it was found to be biocompatible and also improved the mean residence time (MRT) than 5% suspension in tears. Therefore, the developed 1% Natcel could be a potential alternative treatment for fungal keratitis.

Extracellular vesicles from Candida albicans modulate immune cells function and play a protective role in fungal keratitis

Fungal keratitis (FK) is a highly blinding infectious corneal disease caused by pathogenic fungi. Candida albicans (C. albicans) is one of the main pathogens of fungal keratitis. Extracellular vesicles (EVs), lipid bilayer compartments released by almost all living cells, including fungi, have garnered attention for their role in pathogenic microbial infection and host immune responses in recent years. Studies have reported that pretreating the host with fungal EVs can reduce the inflammatory response of the host when attacked by fungi and reduce the lethality of fungal infection. However, there are no studies that have evaluated whether C. albicans EVs can modulate the inflammatory response associated with C. albicans keratitis. Our study revealed that C. albicans EVs could activate the polymorphonuclear cells (PMNs) and promote their secretion of proinflammatory cytokines and nitric oxide (NO), enhance their phagocytic and fungicidal abilities against C. albicans. C. albicans EVs also induced a proinflammatory response in RAW264.7 cells, which is characterized by increased production of inflammatory cytokines and elevated expression of the chemokine CCL2. Similarly, stimulation of C. albicans EVs to RAW264.7 cells also enhanced the phagocytosis and killing ability of cells against C. albicans. Besides, in vivo experiments, after receiving subconjunctival injection of C. albicans EVs, C57BL/6 mice were infected with C. albicans. The results demonstrated that pre-exposure to C. albicans EVs could effectively diminish the severity of keratitis, reduce fungal load and improve prognosis. Overall, we conclude that C. albicans EVs can modulate the function of immune cells and play a protective role in C. albicans keratitis.

An Overview of Prevalence and Treatment of Mycotic Keratitis in India and other Countries in the Indian Subcontinent

An Overview of Prevalence and Treatment of Mycotic Keratitis in India and other Countries in the Indian Subcontinent

Schizophyllum Commune- A Rare Cause of Fungal Keratitis- Case Report and Review of Literature

Abstract We present a 57-year-old male patient with keratitis, he was initially started on topical 0.5% moxifloxacin eye drops, but his symptoms did not resolve and infiltrate continued to increase. Corneal scrapings and microbiological reports suggested the diagnosis of the fungus, Schizophyllum commune, the patient was then switched to topical 5% natamycin eye drops hourly for 1 week followed by eight times per day for 2 weeks and oral tablet fluconazole 200 mg twice daily, following which the infiltrate was reduced, hypopyon resolved and visual acuity improved after 2 weeks of treatment.

A case of Phialemoniopsis curvata keratitis and literature review

We reported the case of a keratomycosis caused by an extremely rare filamentous fungus. A patient with a history of phacoemulsification and intraocular lens implantation surgery followed by bullous keratopathy and was wearing a bandage contact lens presented with signs of keratitis. Microbiological examinations revealed a filamentous fungus identified as Phialemoniopsis curvata. Penetrating keratoplasty was performed due to spontaneous corneal perforation during the treatment. P. curvata is an extremely rare agent of fungal keratitis. Although the course of infection is serious, recovery without sequela may be possible with early diagnosis and appropriate treatment.

Development and Clinical Evaluation of a CRISPR/Cas12a-Based Nucleic Acid Detection Platform for the Diagnosis of Keratomycoses

ObjectiveThe objective of this study was to develop a rapid and accurate CRISPR/Cas12a-based molecular diagnostic assay (Rapid Identification of Mycoses using CRISPR, RID-MyC Assay) to detect fungal nucleic acids and to compare it with existing conventional mycologic methods for the diagnosis of fungal keratitis (FK). DesignThis study was structured as a development and validation study focusing on the creation and assessment of the RID-MyC assay as a novel diagnostic modality for FK. SubjectsParticipants comprised 142 individuals presenting with suspected microbial keratitis at three tertiary care institutions in South India. MethodsThe RID-MyC assay utilized recombinase polymerase amplification (RPA) targeting the 18S rRNA gene for isothermal amplification, followed by a CRISPR/Cas12a reaction. This was benchmarked against microscopy, culture, and polymerase chain reaction (PCR) for the diagnosis of FK. Main Outcome MeasuresThe primary outcome measures focused on the analytical sensitivity and specificity of the RID-MyC assay in detecting fungal nucleic acids. Secondary outcomes measured the assay's diagnostic sensitivity and specificity for FK, including its concordance with conventional diagnostic methods. ResultsThe RID-MyC assay exhibited a detection limit ranging from 13.3 to 16.6 genomic copies across four common fungal species. In patients with microbial keratitis, the RID-MyC assay showed substantial agreement with microscopy (kappa = 0.714) and fair agreement with culture (kappa = 0.399). The assay demonstrated a sensitivity of 93.27% (95% CI, 86.62% - 97.25%) and a specificity of 89.47 % (95% CI, 66.86 % - 98.70 %) for FK diagnosis, with a median diagnostic time of 50 minutes (range, 35 - 124 minutes). ConclusionThe RID-MyC assay, utilizing CRISPR-Cas12a technology, offers high diagnostic accuracy for FK. Its potential for point-of-care use could expedite and enhance the precision of fungal diagnostics, presenting a promising solution to current diagnostic challenges.

Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Traumatic implantation keratitis caused by Schizophyllum commune in Central India

We present two cases with a history of trauma to the cornea and after a few days patients developed symptoms of corneal ulcers with one showing hypopyon as well. Due to strong suspicion of fungal keratitis both cases were treated with topical and intravenously voriconazole. Fungal culture showed white fluffy growth which was identified as Schizophyllum commune by conventional and molecular methods. In both cases surgical intervention was essential. Therapeutic keratoplasty was done in both cases but failed. Unfortunately, both patients lost vision in the affected eyes.

Cathelicidin boosts the antifungal activity of neutrophils and improves prognosis during Aspergillus fumigatus keratitis.

Aspergillus fumigatus (A. fumigatus) is one of the common pathogens of fungal keratitis. Fungal growth and invasion cause excessive inflammation and corneal damage, leading to severe vision loss. Neutrophils are the primary infiltrating cells critical for fungal clearance. Cathelicidin [LL-37 in humans and cathelicidin-related antimicrobial peptide (CRAMP) in mice], a natural antimicrobial peptide, can directly inhibit the growth of many pathogens and regulate immune responses. However, the role of cathelicidin and its effect on neutrophils in A. fumigatus keratitis remain unclear. By establishing A. fumigatus keratitis mouse models, we found that cathelicidin was increased in A. fumigatus keratitis. It could reduce fungal loads, lower clinical scores, and improve corneal transparency. Restriction of CRAMP on fungal proliferation was largely counteracted in CD18-/- mice, in which neutrophils cannot migrate into infected sites. When WT neutrophils were transferred into CD18-/- mice, corneal fungal loads were distinctly reduced, indicating that neutrophils are vital for CRAMP-mediated resistance. Furthermore, cathelicidin promoted neutrophils to phagocytose and degrade conidia both in vitro and in vivo. CXC chemokine receptor 2 (CXCR2) was reported to be a functional receptor of LL-37 on neutrophils. CXCR2 antagonist SB225002 or phospholipase C (PLC) inhibitor U73122 weakened LL-37-induced phagocytosis. Meanwhile, LL-37 induced PLC γ phosphorylation, which was attenuated by SB225002. SB225002 or the autophagy inhibitors Bafilomycin-A1 and 3-Methyladenine weakened LL-37-induced degradation of conidia. Transmission electron microscopy (TEM) observed that LL-37 increased autophagosomes in Aspergillus-infected neutrophils. Consistently, LL-37 elevated autophagy-associated protein expressions (Beclin-1 and LC3-II), but this effect was weakened by SB225002. Collectively, cathelicidin reduces fungal loads and improves the prognosis of A. fumigatus keratitis. Both in vitro and in vivo, cathelicidin promotes neutrophils to phagocytose and degrade conidia. LL-37/CXCR2 activates PLC γ to amplify neutrophils' phagocytosis and induces autophagy to eliminate intracellular conidia.

Clinical efficacy of cyclosporin and natamycin for fungal keratitis.

To investigate the clinical efficacy of cyclosporin (CYSP) and natamycin (NAT) as a combination therapy in patients with fungal keratitis. This is a retrospective study. A total of 64 patients (64 eyes) with fungal keratitis treated by Baoding No.1 Central Hospital between December 2018 and May 2022 according to their treatment methods were divided into a monotherapy (MT) group receiving NAT eye drops solely and a combination therapy (CT) group given CYSP eye drops in addition to the exact treatment provided for the MT group. The clinical responses, visual acuity changes, severity of eye symptoms, and adverse reactions were compared between the two groups. At two and four weeks post-treatment, the CT group had an overall response rate (ORR) significantly higher than that of the MT group (P< 0.05, respectively); both groups showed improved visual acuity and eye symptoms compared with the pre-treatment condition, and these improvements were more pronounced in the CT group (P < 0.05, respectively). Compared with the MT group, the CT group experienced a significantly shorter duration of eye symptoms (P < 0.05). The adverse reaction rate(ARR) was 9.38% in the CT group and 6.25% in the MT group, and the difference was not significant (P > 0.05). Using CYSP and NAT as a combination therapy for fungal keratitis can substantially heighten the therapeutic effects, promote visual acuity recovery, and induce rapid remission of eye symptoms without increasing the risk of adverse reactions.

Deoxynivalenol Damages Corneal Epithelial Cells and Exacerbates Inflammatory Response in Fungal Keratitis.

Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals. The aim of this study was to explore a possible pathogenic role of DON in FK. We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured. The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas. DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.

A rare case of fungal keratitis caused by Tintelnotia destructans

A rare case of fungal keratitis caused by Tintelnotia destructans

Differentiation of acanthamoeba keratitis from other non-acanthamoeba keratitis: Risk factors and clinical features.

Infectious Keratitis is one of the most common ocular emergencies seen by ophthalmologists. Our aim is to identify the risk factors and clinical features of Acanthamoeba Keratitis (AK). This retrospective chart review study was conducted at King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia, and included all the microbial keratitis cases, male and female patients of all ages. The main outcome is the differentiation between various microbial keratitis types. We included 134 consecutive eyes of 126 persons. We had 24 cases of acanthamoeba keratitis, 22 bacterial keratitis, 24 fungal keratitis, 32 herpetic keratitis, and 32 bacterial co-infection. Contact lens wear was found in 33 eyes (24.6%). Among acanthamoeba keratitis patients, 73% were ≤ 39 years of age, and 73% were females (P <0.001). Also, in AK cases, epithelial defect was found in all cases (100%), endothelial plaques were found in 18 eyes (69.2%), 12 cases had radial keratoneuritis (46.2%), and ring infiltrate was found in 53.8% of AK cases. We determined the factors that increase the risk of acanthamoeba infection and the clinical characteristics that help distinguish it from other types of microbial keratitis. Our findings suggest that younger females and patients who wear contact lenses are more likely to develop acanthamoeba keratitis. The occurrence of epitheliopathy, ring infiltrate, radial keratoneuritis, and endothelial plaques indicate the possibility of acanthamoeba infection. Promoting education on wearing contact lenses is essential to reduce the risk of acanthamoeba infection, as it is the most significant risk factor for this infection.

Spectrum and antibiotic sensitivity of bacterial keratitis: a retrospective analysis of eight years in a Tertiary Referral Hospital in Southwest China.

The objective of this study was to investigate the epidemiological characteristics, distribution of isolates, prevailing patterns, and antibiotic susceptibility of bacterial keratitis (BK) in a Tertiary Referral Hospital located in Southwest China. A retrospective analysis was conducted on 660 cases of bacterial keratitis occurring between January 2015 and December 2022. The demographic data, predisposing factors, microbial findings, and antibiotic sensitivity profiles were examined. Corneal trauma emerged as the most prevalent predisposing factor, accounting for 37.1% of cases. Among these cases, bacterial culture results were positive in 318 cases, 68 species of bacteria were identified. The most common Gram-Positive bacteria isolated overall was the staphylococcus epidermis and the most common Gram-Negative bacteria isolated was Pseudomonas aeruginosa. Methicillin-Resistant Staphylococci accounted for 18.1% of all Gram-Positive bacteria. The detection rate of P. aeruginosa showed an increasing trend over time (Rs=0.738, P=0.037). There was a significant decrease in the percentage of Gram-Negative microorganisms over time (Rs=0.743, P=0.035). The sensitivity of Gram-Positive bacteria to linezolid, vancomycin, tigecycline, quinupristin/dalfopristin, and rifampicin was over 98%. The sensitivity rates of Gram-Negative bacteria to amikacin, meropenem, piperacillin/tazobactam, cefoperazone sodium/sulbactam, ceftazidime, and cefepime were all above 85%. In patients with a history of vegetative trauma, the possibility of BK should be taken into account in addition to the focus on fungal keratitis. The microbial composition primarily consists of Gram-Positive cocci and Gram-Negative bacilli. Among the Gram-Positive bacteria, S. epidermidis and Streptococcus pneumoniae are the most frequently encountered, while P. aeruginosa is the predominant Gram-Negative bacteria. To combat Gram-Positive bacteria, vancomycin, linezolid, and rifampicin are considered excellent antimicrobial agents. When targeting Gram-Negative pathogens, third-generation cephalosporins exhibit superior sensitivity compared to first and second-generation counterparts. As an initial empirical treatment for severe cases of bacterial keratitis and those unresponsive to fourth-generation fluoroquinolones in community settings, the combination therapy of vancomycin and tobramycin is a justifiable approach. Bacterial keratitis can be better managed by understanding the local etiology and antibacterial drug susceptibility patterns.

Exploring Heparanase Levels in Tears: Insights From Herpes Simplex Virus-1 Keratitis Patients and Animal Studies.

Heparanase (HPSE) cleaves heparan sulfate proteoglycans during herpes simplex virus-1 (HSV-1) infection, aiding in viral egress and disease progression. Its action has been well established in in vitro and in vivo models, but its relevance in human patients remains unclear. This study aimed to specifically evaluate tear HPSE levels of patients with herpes simplex keratitis (HSK) and to correlate these findings with a commonly used murine model. Tear samples from patient and mice samples were collected at LV Prasad Eye Institute, Hyderabad, India, and at the University of Illinois, Chicago, IL, respectively. Tears were collected from HSV-1 patients, bacterial/fungal keratitis cases, and healthy individuals. For in vivo study, C57BL/6 mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). The HSV-1, bacterial keratitis, fungal keratitis, and healthy control groups each had 30 patients. There was a significant difference in HPSE expression in the HSV-1 infected eyes (1.55 ± 0.19 units/mL) compared to HSV-1 contralateral eyes (1.23 ± 0.13 units/mL; P = 0.82), bacterial keratitis eyes (0.87 ± 0.15 units/mL; P = 0.0078), fungal keratitis eyes (0.64 ± 0.09 units/mL; P < 0.00001), and normal controls (0.53 ± 0.06 units/mL; P < 0.00001). C57BL/6 mice tear HPSE expression in infected eyes was 0.66 to 5.57 ng heparan sulfate (HS) removed per minute when compared to non-infected eye (range, 0.70-3.67 ng HS removed per minute). To the best of our knowledge, this study is the first to report elevated HPSE levels in the tears of patients with different forms of HSV-1 keratitis, and it confirms similar findings in a murine model, providing a valuable basis for future in vivo and clinical research on HSV-1 ocular infection.

Mesoporous zinc oxide-based drug delivery system offers an antifungal and immunoregulatory strategy for treating keratitis

Fungal keratitis is a refractory eye disease that is prone to causing blindness. Fungal virulence and inflammatory responses are two major factors that accelerate the course of fungal keratitis. However, the current antifungal drugs used for treatment usually possess transient residence time on the ocular surface and low bioavailability deficiencies, which limit their therapeutic efficacy. In this work, natamycin (NATA)-loaded mesoporous zinc oxide (Meso-ZnO) was synthesized for treating Aspergillus fumigatus keratitis with excellent drug-loading and sustained drug release capacities. In addition to being a carrier for drug delivery, Meso-ZnO could restrict fungal growth in a concentration-dependent manner, and the transcriptome analysis of fungal hyphae indicated that it inhibited the mycotoxin biosynthesis, oxidoreductase activity and fungal cell wall formation. Meso-ZnO also promoted cell migration and exhibited anti-inflammatory role during fungal infection by promoting the activation of autophagy. In mouse models of fungal keratitis, Meso-ZnO/NATA greatly reduced corneal fungal survival, alleviated tissue inflammatory damage, and reduced neutrophils accumulation and cytokines expression. This study suggests that Meso-ZnO/NATA can be a novel and effective treatment strategy for fungal keratitis.

Locality is the strongest predictor of expert performance in image-based differentiation of bacterial and fungal corneal ulcers from India.

This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography. This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts. Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40). Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.

Fabrication of nanozyme-thixotropic anionic hydrogel coating with multi-enzyme-mimicking activity for the treatment of fungal keratitis

Fungal keratitis is the primary cause of infectious corneal blindness in China. Currently, early-stage treatment mainly involves the frequent administration of antifungal medications to ensure prolonged corneal contact and maintain effective drug concentration. This approach, however, may lead to harmful side effects and increased antifungal resistance due to the substantial use of antifungal agents. Consequently, the development of advanced antifungal strategies is essential. In the study, we fabricated a multi-enzyme-mimicking nanozyme-thixotropic anionic hydrogel coating (NHC) that incorporated voriconazole and copper-proanthocyanidins (CuPC) nanozyme, by the Schiff base reaction of self-synthesized polyaldehyde oligomer (PAO) with amino functionalized hyaluronic acid (AHA), for the treatment of fungal keratitis. The thixotropic anionic hydrogel significantly boosts the retention time and permeability of voriconazole, allowing a low dose to achieve a high therapeutic concentration. Additionally, the inherent antifungal and peroxidase-like activities of CuPC, coupled with the intrinsic characteristics of anionic hydrogel, further enhance the antifungal efficacy of NHC. Moreover, the NHC assists in corneal wound healing through stimulating cell proliferation by HA derivative as well as scavenging ROS via the catalase-like and superoxide dismutase-like activities of CuPC. The in vitro and in vivo studies have illustrated the safety and effectiveness of NHC, indicating its potential in the treatment of fungal keratitis.

Sertaconazole-PLGA nanoparticles for management of ocular keratitis

Ocular fungal infections can pose severe health conditions that may develop into vision impairment and blindness. Sertaconazole (STZ) is a widely used antifungal; however, its low aqueous solubility restricts its topical application for managing ocular keratitis. This investigation aimed to develop polymeric nanoparticles as delivery carriers to improve the ophthalmic availability of STZ for treating fungal keratitis. The impact of STZ solid dispersion incorporation within polymeric nanoparticles for in vitro drug release enhancement was also evaluated. STZ-laden PLGA NPs were formulated via nanoprecipitation technology, using a 24-full factorial layout to optimize the formulation. The formed nanoparticles were assessed for encapsulation efficiency percentage, hydrodynamic size, surface charge, and polydispersity index. The selected formula exhibited a particle size of 305.9 ± 4.36 nm, an entrapment efficiency (EE%) of 98.8 ± 0.008%, a surface charge of 22.57 ± 0.23 mV, and a low polydispersity index, indicating a uniform size distribution. Incorporating STZ in a solid dispersion form with PEG 2000 at a 1:3 w/w drug-to-carrier ratio increased the hydrodynamic size of the PLGA NPs. However, no significant variation in the entrapment efficiency percentage was recorded. The developed STZ-solid dispersion-loaded PLGA NPs have round-shaped structures. DSC and FTIR spectroscopy data indicated drug amorphization with successful loading within the PLGA matrix. Introducing the drug as a solid dispersion within PLGA NPs resulted in enhancing the rate of drug dissolution at initial time intervals, followed by a controlled drug release over 24 h. STZ-PEG2000-laden PLGA NPs enhanced permeability through rabbits’ corneas (Papp), 2.5-fold higher versus STZ-loaded PLGA NPs. The antimycotic activity of the developed formulation was tested against Candida albicans, and a 4-fold reduction in the MIC value was detected upon applying the nanoparticles’ formulation embedding STZ solid dispersion versus that containing the free drug. In conclusion, the formulation of solid dispersions of STZ loaded in PLGA nanoparticles may serve as a starting point for an efficient approach to the ocular delivery of hydrophobic medications and a viable setup for the upcoming research in animal models of fungal keratitis.