Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration

Kambhampati, Siva P.; Bhutto, Imran Ahmed; Wu, Tony; Ho, Katie; McLeod, D. Scott; Lutty, Gerard A.; Kannan, Rangaramanujam M.

doi:10.1016/j.jconrel.2021.05.035

Cited by 34 publications

(31 citation statements)

References 72 publications

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“…A second example of PAMAM hydroxyl dendrimers stochastically functionalized concerned the grafting of known drugs suitable for treating diverse eye diseases. A recent paper published this concept using triamcinolone-acetonide as drug conjugated to the dendrimer and tested in models of age-related macular degeneration [ 52 ]. However, the drug presently under clinical trials is a generation-four PAMAM hydroxyl dendrimer partly functionalized with Sunitinib, an inhibitor of vascular endothelial growth factor receptors (simplified structure in Figure 6 B).…”

Section: Clinical Trials With Pamam Dendrimersmentioning

confidence: 99%

Dendrimers, an Emerging Opportunity in Personalized Medicine?

Caminade

2022

JPM

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Dendrimers are highly branched macromolecules tailorable at will to fulfil precise requirements. They have generated a great many expectations and a huge number of publications and patents in relation to medicine, including in relation to personalized medicine, but have resulted in very poor clinical translation up to now. As clinical trials are the first steps in view of developing new compounds for (a personalized) medicine, this review focusses on the clinical trials carried out with dendrimers. Many of these clinical trials have been recently posted (2020–2022); thus, only very few concern phase 3. The safety and efficiency of essentially two main types of dendrimers, based on polylysine and polyamidoamide scaffolds, have been assessed up to now. These dendrimers were tested with the aim of treating mainly bacterial vaginosis, cancers, and COVID-19.

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Section: Clinical Trials With Pamam Dendrimersmentioning

confidence: 99%

Dendrimers, an Emerging Opportunity in Personalized Medicine?

Caminade

2022

JPM

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“…The application of trimethoprim for anti-VEGF was limited by intraocular injection, which caused side effects such as increased intraocular pressure and retinal toxicity following local crystallization (Yu, Damico et al, 2006;Sonmez and Ozturk 2012). Hydroxyl-terminated polyamidoamine dendrimer-triamcinolone acetonide conjugate (D-TA) was used in AMD rats (Kambhampati, Bhutto et al, 2021). A single intravenous dose of 3 mg/kg was more effective than a 10-fold dose of free triamcinolone acetonide in preventing choroidal neovascularization (CNV).…”

Section: Polymer Nanoparticlesmentioning

confidence: 99%

“…Nano-drug delivery systems are also considered to be superior to conventional drug therapy in the anterior and posterior segment of the eyes (Yadav, Rajpurohit et al, 2019;Jumelle, Gholizadeh et al, 2020;Kambhampati, Bhutto et al, 2021;Li Q et al, 2021). NPs for drug delivery are mainly classified into organic and inorganic NPs .…”

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confidence: 99%

Nanoparticles in ocular applications and their potential toxicity

Cao

Yang

et al. 2022

Front. Mol. Biosci.

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Nanotechnology has been developed rapidly in recent decades and widely applied in ocular disease therapy. Nano-drug delivery systems overcome the bottlenecks of current ophthalmic drug delivery and are characterized with strong biocompatibility, stability, efficiency, sustainability, controllability, and few side effects. Nanoparticles have been identified as a promising and generally safe ophthalmic drug-delivery system based on the toxicity assessment in animals. Previous studies have found that common nanoparticles can be toxic to the cornea, conjunctiva, and retina under certain conditions. Because of the species differences between humans and animals, advanced in vitro cell culture techniques, such as human organoids, can mimic the human organism to a certain extent, bringing nanoparticle toxicity assessment to a new stage. This review summarizes the advanced application of nanoparticles in ocular drug delivery and the potential toxicity, as well as some of the current challenges and future opportunities in nanotoxicological evaluation.

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“…These infiltrating cells further secrete cytokines, proteases and free radicals to damage local tissues. NPs have been demonstrated to inhibit the aggregation of various immune cells at inflammatory sites, including macrophages, eosinophils, lymphocytes, and plasma cells [11,14,29,33,40,57]. NPs may implement this feature by downregulating all kinds of chemotactic molecules [14,39,40,58].…”

Section: Inhibiting Immune Cell Infiltrationmentioning

confidence: 99%

“…Conventional eye drops are often degraded by tears and blinking, which causes much drug wastage, with less than 1-5% of the doses of these drops being delivered to the target tissue [9][10][11][12]. Intravitreal injections run the risk of causing pain, intraocular infections and even partial retinal detachment [13,14]. Hence, novel materials and drug delivery routes need to be developed to replace traditional therapeutic strategies for better treatment effects.…”

Section: Introductionmentioning

confidence: 99%

Immune modulating nanoparticles for the treatment of ocular diseases

Fang

Liu

et al. 2022

J Nanobiotechnol

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Ocular diseases are increasingly influencing people’s quality of life. Complicated inflammatory mechanisms involved in the pathogenic process of ocular diseases make inflammation-targeting treatment a potential therapeutic approach. The limited efficacy of conventional anti-inflammatory therapeutic strategies, caused by various objective factors, such as complex ocular biological barriers, and subjective factors, such as poor compliance, are promoting the development of new therapeutic methods. With the advantages of considerable tissue permeability, a controllable drug release rate, and selective tissue targeting ability, nanoparticles have successfully captured researchers’ attention and have become a research hotspot in treating ocular diseases. This review will focus on the advantages of nanosystems over traditional therapy, the anti-inflammation mechanisms of nanoparticles, and the anti-inflammatory applications of nanoparticles in different ocular diseases (ocular surface diseases, vitreoretinopathy, uveal diseases, glaucoma, and visual pathway diseases). Furthermore, by analyzing the current situation of nanotherapy and the challenges encountered, we hope to inspire new ideas and incentives for designing nanoparticles more consistent with human physiological characteristics to make progress based on conventional treatments. Overall, some progress has been made in nanoparticles for the treatment of ocular diseases, and nanoparticles have rather broad future clinical translation prospects.

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Systemic dendrimer nanotherapies for targeted suppression of choroidal inflammation and neovascularization in age-related macular degeneration

Cited by 34 publications

References 72 publications

Dendrimers, an Emerging Opportunity in Personalized Medicine?

Dendrimers, an Emerging Opportunity in Personalized Medicine?

Nanoparticles in ocular applications and their potential toxicity

Immune modulating nanoparticles for the treatment of ocular diseases

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