Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone

Barcia, Emilia; Herrero-Vanrell, Rocı́o; Díez, Á.; Alvarez-Santiago, Consuelo; López, Isabel Miguel; Calonge, Margarita

doi:10.1016/j.exer.2009.03.012

Cited by 65 publications

(38 citation statements)

References 35 publications

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“…2 Among different biodegradable polymers for ocular drug delivery, PLGA copolymers have been used more frequently as vehicles. 9,10 PLC copolymers are relatively new, and very few ocular applications are reported in the literature.…”

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confidence: 99%

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

Liu

Peng

Lwin

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Liu YC, Peng Y, Lwin NC, Wong TT, Venkatraman SS, Mehta JS. Optimization of subconjunctival biodegradable microfilms for sustained drug delivery to the anterior segment in a small animal model. Invest Ophthalmol Vis Sci. 2013;54:260754: -261554: . DOI: 10.1167 PURPOSE. We evaluated a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly[d,l-lactide-co-e-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics in vitro and in vivo.METHODS. Blank and 40% PA-loaded PLC microfilms with a diameter of 2 mm were fabricated, and the degradation and drug release profiles of the microfilms were characterized in vitro and in vivo. The microfilms were implanted into the subconjunctival space of Lewis rats (n ¼ 48). All eyes were assessed clinically using slit-lamp biomicroscopy, and graded with HackettMcDonald ocular scoring system and anterior segment optical coherence tomography. Histologic and immunohistochemical analyses were performed comparing blank and PAloaded microfilm groups. PA concentrations in the aqueous humor were determined by HPLC.RESULTS. Subconjunctivally-implanted PLC microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/d in vivo. Eyes with either blank or PAloaded implanted microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the microfilms, with significantly less CD11c cells at 2 and 4 weeks (P ¼ 0.001 and P ¼ 0.002), and collagen formation at 2 weeks (P ¼ 0.001) in the PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7 6 5.9, 70.3 6 2.3, and 42.7 6 4.1 ng/mL at 2, 4, and 12 weeks, respectively.CONCLUSIONS. PA-loaded PLC microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, and have the potential to exhibit antifibrotic and antiinflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.

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confidence: 99%

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

Liu

Peng

Lwin

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…These approaches permit a sustained and stable multifold increase in drug concentration to reach the retina without inducing systemic side effects while improving therapeutic outcome. Sustained-drug release intraocular implants for delivery of triamcinalone [146] and polylactic-glycolic acid microspheres to deliver dexamethasone [147] to treat diabetic retinal complications and inflammation have been used successfully [148]. Lipid nanoparticles have been used to deliver bevacizumab directly into the vitreous of rabbits with the result of chronically increasing the concentration and bioavailability of the drug in the vitreous several folds [149].…”

Section: Multiple Options and Opportunities To Minimize Undesirabmentioning

confidence: 99%

Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

Jacot

Sherris

2011

Journal of Ophthalmology

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Novel therapeutics such as inhibitors of PI3K/Akt/mTOR pathway presents a unique opportunity for the management of diabetic retinopathy (DR). Second generation mTOR inhibitors have the prospect to be efficacious in managing various stages of disease progression in DR. During early stages, the mTOR inhibitors suppress HIF-1α, VEGF, leakage, and breakdown of the blood-retinal barrier. These mTOR inhibitors impart a pronounced inhibitory effect on inflammation, an early component with diverse ramifications influencing the progression of DR. These inhibitors suppress IKK and NF-κB along with downstream inflammatory cytokines, chemokines, and adhesion molecules. In proliferative DR, mTOR inhibitors suppress several growth factors that play pivotal roles in the induction of pathological angiogenesis. Lead mTOR inhibitors in clinical trials for ocular indications present an attractive treatment option for chronic use in DR with favorable safety profile and sustained ocular pharmacokinetics following single dose. Thereby, reducing dosing frequency and risk associated with chronic drug administration.

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“…To facilitate the injection of the microspheres, they were suspended in a sterile aqueous solution containing 0.5% HPMC. 19 …”

Section: Preparation Of Microspheresmentioning

confidence: 99%

“…[14][15][16][17] Among various biodegradable polymers, poly(lactic-co-glycolic acid) (PLGA) is the most widely studied and used. 16,18,19 In this study, we first prepared sustained-release voriconazole microspheres (VCZ-MS). Then, choosing Aspergillus fumigatus as our model pathogen due to its powerful pathogenicity, we established an animal model of exogenous fungal endophthalmitis that was similar to human endophthalmitis caused by trauma.…”

Section: Introductionmentioning

confidence: 99%

Anti-Infectious Activity of Intravitreal Injectable Voriconazole Microspheres on Experimental Rabbit Fungal Endophthalmitis Caused by aspergillus fumigatus

Yang

Meng

et al. 2011

Journal of Pharmaceutical Sciences

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Downregulation of endotoxin-induced uveitis by intravitreal injection of polylactic-glycolic acid (PLGA) microspheres loaded with dexamethasone

Cited by 65 publications

References 35 publications

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model

Potential Therapeutic Roles for Inhibition of the PI3K/Akt/mTOR Pathway in the Pathophysiology of Diabetic Retinopathy

Anti-Infectious Activity of Intravitreal Injectable Voriconazole Microspheres on Experimental Rabbit Fungal Endophthalmitis Caused by aspergillus fumigatus

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