Controlled Release of Vancomycin From a Thermoresponsive Hydrogel System for the Prophylactic Treatment of Postoperative Acute Endophthalmitis

Dosmar, Emily; Liu, Wenqiang; Patel, Geeya; Rogozinski, Alison; Mieler, William F.; Kang-Mieler, Jennifer J.

doi:10.1167/tvst.8.3.53

Cited by 12 publications

(15 citation statements)

References 40 publications

(64 reference statements)

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“…It should be noted that in a previous study, this DDS was evaluated in a rodent model and was able to successfully prevent infection in the vitreous within the first 24 h following exposure to Staphylococcus aureus bacteria and placement in the subconjunctival space. These results suggest that the minimum therapeutic dose can be and is achieved in vivo [44].…”

Section: Discussionmentioning

confidence: 70%

“…An amount of 34 mg of VAN was successfully encapsulated into 1 mL PNIPAAm-PEG-DA thermo-responsive hydrogels following washing (data previously published [44]), yielding an EE of 57%. The initial VAN releases from these hydrogels were 23% ± 0.1, 31% ± 0.95 and 36% ± 0.06 at 6, 12 and 24 h, respectively (Figure 2A).…”

Section: In Vitro Drug Delivery System Resultsmentioning

confidence: 99%

Section: Compartmental Modelmentioning

confidence: 99%

“…Thresholds: We have previously determined, empirically, the minimum therapeutic dose for VAN [44]. Considering a vitreous size of 1 cm 2 , 0.007 mg/mL is considered a therapeutic does to kill bacteria on the total surface area [44]. A study completed by Souli et al (2001) measured a peak VAN concentration of 24.82 µg/mL ± 3.55 µg/mL in the human aqueous humor following bolus subconjunctival injections [10].…”

Section: Compartmental Modelmentioning

confidence: 99%

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Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Dosmar

Vuotto

et al. 2021

Pharmaceutics

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The purpose of this study was to examine antibiotic drug transport from a hydrogel drug delivery system (DDS) using a computational model and a 3D model of the eye. Hydrogel DDSs loaded with vancomycin (VAN) were synthesized and release behavior was characterized in vitro. Four different compartmental and four COMSOL models of the eye were developed to describe transport into the vitreous originating from a DDS placed topically, in the subconjunctiva, subretinally, and intravitreally. The concentration of the simulated DDS was assumed to be the initial concentration of the hydrogel DDS. The simulation was executed over 1500 and 100 h for the compartmental and COMSOL models, respectively. Based on the MATLAB model, topical, subconjunctival, subretinal and vitreous administration took most (~500 h to least (0 h) amount of time to reach peak concentrations in the vitreous, respectively. All routes successfully achieved therapeutic levels of drug (0.007 mg/mL) in the vitreous. These models predict the relative build-up of drug in the vitreous following DDS administration in four different points of origin in the eye. Our model may eventually be used to explore the minimum loading dose of drug required in our DDS leading to reduced drug use and waste.

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Section: Discussionmentioning

confidence: 70%

Section: In Vitro Drug Delivery System Resultsmentioning

confidence: 99%

Section: Compartmental Modelmentioning

confidence: 99%

Section: Compartmental Modelmentioning

confidence: 99%

See 2 more Smart Citations

Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Dosmar

Vuotto

et al. 2021

Pharmaceutics

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“…6 and Table 1). 84 The PEG-DA/PNIPAAm copolymer released VAN at a steady rate for 2 weeks before reaching a plateau regimen after 3 weeks. The conjunctivas and corneas of animals receiving the VAN-loaded PEG-DA/PNIPAAm formulations were effectively treated as verified by the eyes without observable signs of infection (such as clouding of the cornea and redness in the conjunctiva) throughout the follow-up period of 72 h. These results were further confirmed by the results of histopathological sections of the vitreous body.…”

Section: Ocular Infectionmentioning

confidence: 99%

Advancing the stimuli response of polymer-based drug delivery systems for ocular disease treatment

Nguyen

Lai

2020

Polym. Chem.

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Vision Defense: Efficient Antibacterial AIEgens Induced Early Immune Response for Bacterial Endophthalmitis

Cai

et al. 2022

Advanced Science

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Bacterial endophthalmitis (BE) is an acute eye infection and potentially irreversible blinding ocular disease. The empirical intravitreous injection of antibiotic is the primary treatment once diagnosed as BE. However, the overuse of antibiotic contributes to the drug resistance of pathogens and the retinal toxicity of antibiotic limits its application in clinic. Herein, a cationic aggregation-induced emission luminogens named with triphenylamine thiophen pyridinium (TTPy) is reported for photodynamic treatment of BE. TTPy can selectively discriminate and kill bacteria efficiently over normal ocular cells. More importantly, TTPy shows excellent antibacterial ability in BE rat models infected by Staphylococcus aureus. Meanwhile, the bacterial killing behavior triggered by TTPy induces innate immune response at an early stage of infection, limiting subsequent robust inflammation and protecting retina from bacterial toxins and inflammation-induced bystander damage. In addition, TTPy performs better antibacterial ability than commercially used Rose Bengal, suggesting its excellent capability of vision salvage in acute BE. This study exhibits an efficient photodynamic antibacterial treatment to BE, which induces an early intraocular immune response and saves useful vision, endowing TTPy a promising potential for clinical application of ocular infections.

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Controlled Release of Vancomycin From a Thermoresponsive Hydrogel System for the Prophylactic Treatment of Postoperative Acute Endophthalmitis

Abstract: Mieler JJ. Controlled release of vancomycin from a thermoresponsive hydrogel system for the prophylactic treatment of postoperative acute endophthalmitis.

Cited by 12 publications

References 40 publications

Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Compartmental and COMSOL Multiphysics 3D Modeling of Drug Diffusion to the Vitreous Following the Administration of a Sustained-Release Drug Delivery System

Advancing the stimuli response of polymer-based drug delivery systems for ocular disease treatment

Vision Defense: Efficient Antibacterial AIEgens Induced Early Immune Response for Bacterial Endophthalmitis

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