Intravitreally Implantable Voriconazole Delivery System for Experimental Fungal Endophthalmitis

Lu, Yang; Dong, Xiaoguang; Wu, Xianggen; Xie, Lixin; Min, Xiaojie

doi:10.1097/iae.0b013e31820d3cd2

Cited by 6 publications

(7 citation statements)

References 42 publications

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“…A literature review indicated that few drug delivery systems have been developed and their efficacy evaluated in animals. In one attempt, the therapeutic effect demonstrated by an intravitreal drug delivery system of voriconazole was superior to intravitreal injection in rabbits [ 7 ]. Chitosan nanoparticles containing daptomycin were developed in ocular treatment of bacterial endophthalmitis.…”

Section: Introductionmentioning

confidence: 99%

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

et al. 2021

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Solid lipid nanoparticles (SLNs) are being extensively exploited as topical ocular carrier systems to enhance the bioavailability of drugs. This study investigated the prospects of drug-loaded SLNs to increase the ocular permeation and improve the therapeutic potential of clarithromycin in topical ocular therapy. SLNs were formulated by high-speed stirring and the ultra-sonication method. Solubility studies were carried out to select stearic acid as lipid former, Tween 80 as surfactant, and Transcutol P as cosurfactant. Clarithromycin-loaded SLN were optimized by fractional factorial screening and 32 full factorial designs. Optimized SLNs (CL10) were evaluated for stability, morphology, permeation, irritation, and ocular pharmacokinetics in rabbits. Fractional factorial screening design signifies that the sonication time and amount of lipid affect the SLN formulation. A 32 full factorial design established that both factors had significant influences on particle size, percent entrapment efficiency, and percent drug loading of SLNs. The release profile of SLNs (CL9) showed ~80% drug release in 8 h and followed Weibull model kinetics. Optimized SLNs (CL10) showed significantly higher permeation (30.45 μg/cm2/h; p < 0.0001) as compared to control (solution). CL10 showed spherical shape and good stability and was found non-irritant for ocular administration. Pharmacokinetics data demonstrated significant improvement of clarithromycin bioavailability (p < 0.0001) from CL10, as evidenced by a 150% increase in Cmax (~1066 ng/mL) and a 2.8-fold improvement in AUC (5736 ng h/mL) (p < 0.0001) as compared to control solution (Cmax; 655 ng/mL and AUC; 2067 ng h/mL). In summary, the data observed here demonstrate the potential of developed SLNs to improve the ocular permeation and enhance the therapeutic potential of clarithromycin, and hence could be a viable drug delivery approach to treat endophthalmitis.

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Section: Introductionmentioning

confidence: 99%

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

et al. 2021

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“…This, in part, could be due to limited or unavailability of appropriate fungal endophthalmitis animal models. However, few earlier studies have utilized guinea pig [21] and rabbit [22,23] models to test the therapeutic efficacy of antifungal agents in Aspergillus fumigatus (AF) endophthalmitis. Similarly, we evaluated isavuconazole for the treatment of AF endophthalmitis in a mouse model [11].…”

Section: Introductionmentioning

confidence: 99%

Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice

et al. 2019

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Despite Aspergillus being the leading cause of exogenous fungal endophthalmitis following traumatic injury to the eye, its pathogenesis is not fully understood. In the current study, we developed a murine model of Aspergillus fumigatus (AF) endophthalmitis and investigated the disease pathobiology. Endophthalmitis was induced by intravitreal injection of Aspergillus spores in immunocompetent and immunocompromised (neutropenic) C57BL/6 mice, and disease severity was assessed by eye exam, fungal burden estimation, and histological examination. Our data showed that AF infection caused a time-dependent increase in corneal haze, opacity, and hypopyon beginning at two days post-infection (DPI). The fungal burden in infected eyes of immunocompetent mice peaked at 2 DPI and declined over 9 DPI. AF-infected neuroretina exhibited induction of innate immune response via upregulation of Toll-like receptors (TLRs) and inflammatory mediators (TNFα, IL-1β, and IL6), and increased polymorphonuclear neutrophil (PMN) infiltration. Histological analysis revealed heavy cellular infiltrates in the vitreous cavity as well as disruption of normal retinal architecture and increased retinal cell death. Neutropenic mice exhibited severe disease pathology with the prolonged fungal burden and increased inflammatory mediators. Our study described the first immunocompetent murine model of exogenous AF endophthalmitis and demonstrated an important role of neutrophils in innate defense against fungal endophthalmitis.

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“…68 Future options for the treatment of Pseudallescheria endophthalmitis could include the use of these compounds, possible combinations of existing antifungal agents, or even novel antifungal delivery devices for fungal endophthalmitis like the use of polylactic-coglycolic acid polymers. 69 In summary, Pseudallescheria endophthalmitis is a devastating condition that is more common than previously described. To ensure the overall care of the patient, involvement of infectious disease specialists and other physicians is crucial.…”

Section: Pseudallescheria Endophthalmitis Moloney and Parkmentioning

confidence: 95%

Pseudallescheria Endophthalmitis

Moloney

Park

2014

Retina

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Intravitreally Implantable Voriconazole Delivery System for Experimental Fungal Endophthalmitis

Abstract: The therapeutic effect of intravitreal VCZ DDS on fungal endophthalmitis appears to be significantly better than intravitreal injection of VCZ. The optimal dose of VCZ in the DDS in this study was 1.2 mg.

Cited by 6 publications

References 42 publications

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Clarithromycin Solid Lipid Nanoparticles for Topical Ocular Therapy: Optimization, Evaluation and In Vivo Studies

Pathobiology of Aspergillus Fumigatus Endophthalmitis in Immunocompetent and Immunocompromised Mice

Pseudallescheria Endophthalmitis

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