Therapeutic and Toxicological Evaluations of Cyclosporine A Microspheres as a Treatment Vehicle for Uveitis in Rabbits

He, Yuan; Wang, Jiancheng; Liu, Yuling; Ma, Zhizhong; Zhu, Xiuan; Zhang, Qiang

doi:10.1089/jop.2006.22.121

Cited by 30 publications

(15 citation statements)

References 18 publications

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“…There are many papers concerned with the toxicological and safety profiles of PLGA, and our data concur with these in demonstrating the safety of the materials (Semete et al, 2010;He et al, 2006;Hara et al, 2008). In one example of this, Kang implanted PLGA films into rats and mice, and observed toxicity and biocompatibility over 24 weeks .…”

Section: Tablesupporting

confidence: 80%

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Williams

Branford-White

et al. 2016

European Journal of Pharmaceutical Sciences

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In this work, we sought to generate sustained-release injectable microspheres loaded with the GLP-1 analogue liraglutide. Using water-in-oil-in-water double emulsion methods, poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with liraglutide were prepared. The microspheres gave sustained drug release over 30days, with cumulative release of up to 90% reached in vitro. The microspheres were further studied in a rat model of diabetes, and their performance compared with a group given daily liraglutide injections. Reduced blood sugar levels were seen in the microsphere treatment groups, with the results being similar to those obtained with conventional injections between 10 and 25days after the commencement of treatment. After 5 and 30days of treatment, the microspheres seem a little slower to act than the injections. The pathology of the rats' spleen, heart, kidney and lungs was probed after the 30-day treatment period, and the results indicated that the microspheres were safe and had beneficial effects on the liver, reducing the occurrence of fatty deposits seen in untreated diabetic rats. Moreover, in terms of liver, renal and cardiac functions, and blood lipid and antioxidant levels, the microspheres were as effective as the injections. The expression of several proteases linked to the metabolism of aliphatic acids and homocysteine was promoted by the microsphere formulations. Inflammatory markers in the microsphere treatment groups were somewhat higher than the injection group, however. The liraglutide/PLGA microspheres prepared in this work are overall shown to be efficacious in a rat model of diabetes, and we thus believe they have strong potential for clinical use.

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Section: Tablesupporting

confidence: 80%

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Williams

Branford-White

et al. 2016

European Journal of Pharmaceutical Sciences

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“…However, there are limitations (low bioavailability and systemic side effects) associated with the commonly used formulations of cyclosporine (topically, systemically administered). [266,267] To overcome these limitations, microparticles containing cyclosporine have been under investigation as an alternative system for delivering the drug for a prolonged period of time, thus achieving a prolonged drug action with reduced side effects (Figure 12A). [86,266] In particular, it has been demonstrated that PLGA-based microparticles containing cyclosporine allow for a sustained concentration of the drug in the iris-ciliary body and choroid-retina of healthy rabbits for at least 65 days after injection (Figure 12B).…”

Section: Ocular Diseasesmentioning

confidence: 99%

“…[266,267] To overcome these limitations, microparticles containing cyclosporine have been under investigation as an alternative system for delivering the drug for a prolonged period of time, thus achieving a prolonged drug action with reduced side effects (Figure 12A). [86,266] In particular, it has been demonstrated that PLGA-based microparticles containing cyclosporine allow for a sustained concentration of the drug in the iris-ciliary body and choroid-retina of healthy rabbits for at least 65 days after injection (Figure 12B). [86] Moreover, the mean residence time of the drug loaded in the microparticles was ten times higher than cyclosporine solution.…”

Section: Ocular Diseasesmentioning

confidence: 99%

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Ratay

Bellotti

Gottardi³

et al. 2017

Adv Healthcare Materials

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Dry eye disease (DED), age-related macular degeneration (AMD), and Uveitis are ocular diseases that significantly affect the quality of life of millions of people each year. In these diseases, the action of chemokines, pro-inflammatory cytokines, and immune cells drives a local inflammatory response that results in ocular tissue damage. Multiple therapeutic strategies have been developed to either address the symptoms or abate the underlying cause of these diseases. Herein, we will review the challenges to deliver drugs to the relevant location in the eye for each of these diseases as well as current and innovative therapeutic approaches that attempt to restore homeostasis within the ocular microenvironment.

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“…A PLGA cyclosporine microsphere delivery system significantly decreased severity of cellular infiltrate, leukocyte number, and protein levels in eyes of rabbits with uveitis without long-term toxicity [40]. A separate rabbit study demonstrated that cyclosporine A conjugated to a polycaprolactone (PCL)/PLGA copolymer was more effective in treating chronic uveitis when compared to oral cyclosporine [41].…”

Section: Investigational Implantsmentioning

confidence: 99%

Drug Delivery Implants in the Treatment of Vitreous Inflammation

Wang

Jiang

Joshi

et al. 2013

Mediators of Inflammation

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The eye is a model organ for the local delivery of therapeutics. This proves beneficial when treating vitreous inflammation and other ophthalmic pathologies. The chronicity of certain diseases, however, limits the effectiveness of locally administered drugs. To maintain such treatments often requires frequent office visits and can result in increased risk of infection and toxicity to the patient. This paper focuses on the implantable devices and particulate drug delivery systems that are currently being implemented and investigated to overcome these challenges. Implants currently on the market or undergoing clinical trials include those made of nonbiodegradable polymers, containing ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and ranibizumab, and biodegradable polymers, containing dexamethasone, triamcinolone acetonide, and ranibizumab. Investigational intravitreal implants and particulate drug delivery systems, such as nanoparticles, microparticles, and liposomes, are also explored in this review article.

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Therapeutic and Toxicological Evaluations of Cyclosporine A Microspheres as a Treatment Vehicle for Uveitis in Rabbits

Abstract: The CsA-PLGA-MS preparation might be useful in the treatment of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.

Cited by 30 publications

References 18 publications

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

Modern Therapeutic Approaches for Noninfectious Ocular Diseases Involving Inflammation

Drug Delivery Implants in the Treatment of Vitreous Inflammation

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