Intravitreal Injection of Liposome-Encapsulated Ganciclovir in a Rabbit Model

Peyman, Gholam A.; Khoobehi, Bahram; Tawakol, Magdy E.; Schulman, Joel A.; Mortada, Hassan Aly; Alkan, Hay At; Fiscella, Richard G.

doi:10.1097/00006982-198707040-00005

Cited by 53 publications

(17 citation statements)

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“…Therefore, attempts have been made to develop controlled drug delivery systems for vitreoretinal tissue that are able to deliver a drug for a long enough time from a single intravitreal injection. To maintain the long-term vitreous concentration of drugs in the therapeutic range, intraocular drug delivery systems have been investigated by many researchers [3][4][5][6][7][8][9][10][11]. Recently, we have developed injectable drug delivery systems using biodegradable, poly(DLlactide-co-glycolide) microspheres and liposomes [4,5].…”

Section: Introductionmentioning

confidence: 99%

Effect of Particle Size of Polymeric Nanospheres on Intravitreal Kinetics

Sakurai¹,

Ozeki²,

Kunou³

et al. 2000

Ophthalmic Res

136

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In this study, we injected nanospheres containing a fluorescein derivative into the vitreous cavity of pigmented rabbit eyes and evaluated their intraocular kinetics as drug carriers in vivo. Polystyrene nanospheres (2 µm, 200 nm and 50 nm in diameter) containing a fluorescein derivative were used in this study. A suspension of each particle was prepared by diluting with distilled water at a concentration of 10 µg/ml equivalent to sodium fluorescein. The suspension of nanospheres was injected once into the vitreous cavity of unilateral eyes of pigmented rabbits. A sodium fluorescein solution of the same concentration was injected once into the vitreous cavity of the other eye as the control. The intraocular kinetics of nanospheres was evaluated by measuring vitreous fluorescence using a scanning fluorophotometer. To investigate elimination pathways of nanospheres in detail, serial cross-sections of the eyes were examined with a fluorescence microscope. The fluorescence derived from nanospheres was observed in the vitreous cavity for over 1 month (2 µm: t_1/2 = 5.4 ± 0.8 days, 200 nm: t_1/2 = 8.6 ± 0.7 days, 50 nm: t_1/2 = 10.1 ± 1.8 days), whereas that in the control eyes completely disappeared within 3 days (t_1/2 = 7.8 ± 0.7 h). The elimination half-life from the vitreous cavity correlated well with the particle diameter (r = –0.997, p = 0.007). Histological studies using a fluorescence microscope revealed that nanospheres with a diameter of 2 µm were seen in the vitreous cavity and trabecular meshwork, while nanospheres with a diameter of smaller than 200 nm were also observed in the retina as well as these tissues. Our findings indicated that nanospheres may be beneficial as a drug carrier to the retina, vitreous and trabecular meshwork.

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Section: Introductionmentioning

confidence: 99%

Effect of Particle Size of Polymeric Nanospheres on Intravitreal Kinetics

Sakurai¹,

Ozeki²,

Kunou³

et al. 2000

Ophthalmic Res

136

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“…This contributes to prevention of peak concentration, and maintains the therapeutic drug level for a longer period of time. Preliminary work in our laboratory [5,9,16,18] and by other investigators [2,20,22] has demonstrated that intravitreally administered liposome-encapsulated drugs have potential in effective drug delivery for various ocular diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Repeated injection, however, can be accompanied by complications such as lens or retinal injury. To avoid these complications, efforts have been made to entrap drugs within liposomes [5,9,16,18,22]. These lipid vesicles release the drug slowly, thereby reducing the toxicity of drugs and maintaining desired drug concentrations for a long period of time.…”

Section: Introduction Methodsmentioning

confidence: 99%

Intravitreal liposome-encapsulated drugs: A preliminary human report

et al. 1988

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Intravitreal liposome-encapsulated antibiotics and antiviral drugs were used in patients with acute toxoplasmosis retinochoroiditis, presumed propionibacterium acne endophthalmitis after cataract surgery, and presumed cytomegalovirus retinitis associated with AIDS. A single intravitreal dose was effective in the treatment of all the conditions. Intravitreal liposomes may prove to be an advantageous drug delivery system for the treatment of chronic intraocular inflammatory disorders.

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“…25 Because of these characteristics, studies have been conducted on the intravitreal injection of drug-bearing liposomes and have demonstrated that the release of the drug can be controlled, the half-life of the drug inside the vitreous body can be prolonged, and the toxicity of the drug can be reduced. [26][27][28][29][30][31] With the goal of eventually using liposome-encapsulated ganciclovir (GCV) for the treatment of cytomegalovirus retinitis in acquired immune deficiency syndrome (AIDS) patients, liposome-encapsulated GCV and free GCV were injected into the vitreous body of rabbits in a previous study. 32 The intraocular concentration of GCV was determined by an enzyme linked immunosorbent assay (ELISA) assay of the vitreous after a single intravitreal injection of different doses of the free drug (0.2-20 mg) or 1 mg of liposomeencapsulated GCV.…”

Section: Liposomesmentioning

confidence: 99%

Liposomes and nanotechnology in drug development: focus on ocular targets

Honda¹,

Asai²,

Oku³

et al. 2013

IJN

125

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Abstract:Poor drug delivery to lesions in patients' eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood-retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/ nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases.

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Intravitreal Injection of Liposome-Encapsulated Ganciclovir in a Rabbit Model

Cited by 53 publications

References 0 publications

Effect of Particle Size of Polymeric Nanospheres on Intravitreal Kinetics

Effect of Particle Size of Polymeric Nanospheres on Intravitreal Kinetics

Intravitreal liposome-encapsulated drugs: A preliminary human report

Liposomes and nanotechnology in drug development: focus on ocular targets

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