Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated
            into solid lipid nanoparticles and polymeric nanocapsules

Freitas, Luiz Guilherme Azevedo de; Isaac, David Leonardo Cruvinel; Lima, Eliana Martins; Souza, Leonardo Gomes de; Abud, Murilo Alves; Reis, Ricardo Prado Abreu; Tannure, William Thomas; Ávila, Marcos Pereira de

doi:10.5935/0004-2749.20180079

Cited by 17 publications

(4 citation statements)

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“…Abrishami et al injected solid lipid nanoparticle-conjugated diclofenac intravitreally and found that mild improvement in drug efficacy occurred in the intraocular space [102]. After sunitinib-encapsulated solid lipid nanoparticles were administered intravitreally into rabbit eyes, drug efficacy was enhanced [103].…”

Section: Solid Lipid Nanoparticlesmentioning

confidence: 99%

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

2021

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Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.

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Section: Solid Lipid Nanoparticlesmentioning

confidence: 99%

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

2021

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“…Although polymers of nanospheres and nanocapsules are generally non-toxic to the ocular surface, the molecules may cause irritation and immune reactions, especially when applied in intraocular tissues [ 104 , 105 ]. Poly(lactic- co -glycolic acid) (PLGA) nanocapsules have been found to cause cytoplasmic vacuole formation in rabbits [ 106 ]. Intravitreal injection of nude PLGA nanospheres could cause foreign body reactions and induction of monocyte chemoattractant protein 1, macrophage inflammatory protein 1α (MIP-1α), MIP-1β, interleukin-8, tumor necrosis factor-α, interleukin-6, and interleukin-1ra in non-human primates [ 107 ].…”

Section: Innovations That Increase Intraocular Bioavailability Of Topical Drugsmentioning

confidence: 99%

The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye

Wang

Zhou

Zhang³

2021

Ophthalmol Ther

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The prevalence of chronic fundus diseases is increasing with the aging of the general population. The treatment of these intraocular diseases relies on invasive drug delivery because of the globular structure and multiple barriers of the eye. Frequent intraocular injections bring heavy burdens to the medical care system and patients. The use of topical drugs to treat retinal diseases has always been an attractive solution. The fast development of new materials and technologies brings the possibility to develop innovative topical formulations. This article reviews anatomical and physiological barriers of the eye which affect the bioavailability of topical drugs. In addition, we summarize innovative topical formulations which enhance the permeability of drugs through the ocular surface and/or extend the drug retention time in the eye. This article also reviews the differences of eyes between different laboratory animals to address the translational challenges of preclinical models. The fast development of in vitro eye models may provide more tools to increase the clinical translationality of topical formulations for intraocular diseases. Clinical successes of topical formulations rely on continuous and collaborative efforts between different disciplines.

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“…66 Intravitreal injected sunitinib-encapsulated solid lipid nanoparticles exhibited good ocular safety profiles in rabbits. 122 Apaolaza et al reported that, when the reporter green fluorescent protein (GFP) and retinoschisin-loaded solid lipid nanoparticles were intravitreally or subretinally injected to the Rs1h-deficient mice, GFP and retinoschisin were expressed throughout the retinal layers except the outer nuclear layer (ONL), and the expression could maintain for more than two months after the subretinal injection. 65 A partial recovery of the retina in Rs1hdeficient mice was also found.…”

Section: Nanoparticle Drug Delivery To the Retinamentioning

confidence: 99%

“…Tobramycin-encapsulated solid lipid nanoparticles were able to reach the retina 1 h after topical administration or intravenous injection, while nearly no drug could be detected in the retina after topical instillation of the commercially marketed tobramycin (Tobral) or intravenous injection of tobramycin solution at the same concentration . Intravitreal injected sunitinib-encapsulated solid lipid nanoparticles exhibited good ocular safety profiles in rabbits . Apaolaza et al reported that, when the reporter green fluorescent protein (GFP) and retinoschisin-loaded solid lipid nanoparticles were intravitreally or subretinally injected to the Rs1h-deficient mice, GFP and retinoschisin were expressed throughout the retinal layers except the outer nuclear layer (ONL), and the expression could maintain for more than two months after the subretinal injection .…”

Section: Nanoparticle Drug Delivery To the Retinamentioning

confidence: 99%

Nanoparticulate Drug Delivery to the Retina

Weng

Wong

et al. 2020

Mol. Pharmaceutics

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Retinal diseases, such as age-related macular degeneration and diabetic retinopathy, are the leading causes of blindness worldwide. The mainstay of treatment for these blinding diseases remains to be surgery, and the available pharmaceutical therapies on the market are limited, partially owing to various biological barriers in hindering the delivery of therapeutics to the retina. The nanoparticulate drug delivery system confers the capability for delivering therapeutics to the specific ocular targets and, hence, potentially revolutionizes the current treatment landscape of retinal diseases. While the research to date indicates the enormous therapeutics potentials of the nanoparticulate delivery systems, the successful translation of these systems from the bench to bedside is challenging and requires a combined understanding of retinal pathology, physiology of the eye, and particle and formulation designs of nanoparticles. To this end, the review begins with an overview of the most prevalent retinal diseases and related pharmacotherapy. Highlights of the current challenges encountered in ocular drug delivery for each administration route are provided, followed by critical appraisal of various nanoparticulate drug delivery systems for the retinal diseases, including their formulation designs, therapeutic merits, limitations, and future direction. It is believed that a greater understanding of the nano-biointeraction in eyes will lead to the development of more sophisticated drug delivery systems for retinal diseases.

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Retinal changes in rabbit after intravitreal injection of sunitinib encapsulated into solid lipid nanoparticles and polymeric nanocapsules

Cited by 17 publications

References 0 publications

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

The Emerging Role of Topical Ocular Drugs to Target the Posterior Eye

Nanoparticulate Drug Delivery to the Retina

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