In vivo effect of bevacizumab-loaded albumin nanoparticles in the treatment of corneal neovascularization

Redín, Inés Luis de; Boiero, Carolina; Recalde, Sergio; Agüeros, Maite; Allemandi, Daniel Alberto; Llabot, Juan Manuel; García‐Layana, Alfredo; Irache, Juan M.

doi:10.1016/j.exer.2019.107697

Cited by 41 publications

(41 citation statements)

References 45 publications

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“…Reduced inflammation, fibroblast activity and edema were observed when animals were treated with this nanoparticulate system. Despite the bioadhesive properties of polymer PEG, the surface modification in these nanoparticles with this polymer (“ pegylation ”) did not offer any improvement to the antiangiogenic effect of bevacizumab 123 . On the other hand, the preparation of human serum albumin nanoparticles to load bevacizumab with crosslinking agents as stabilizers, was explored.…”

Section: Nanoparticulate Systems For Bd Delivery Intended For Ocular mentioning

confidence: 99%

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Formica

Alfonso

Palma

2021

Pharmacology Res & Perspec

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Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti‐VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off‐label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti‐VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti‐VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti‐VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer‐reviewed published papers relevant to anti‐VEGF treatments and nanoparticles developed as ocular anti‐VEGF delivery system.

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Section: Nanoparticulate Systems For Bd Delivery Intended For Ocular mentioning

confidence: 99%

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Formica

Alfonso

Palma

2021

Pharmacology Res & Perspec

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“…Similar to microparticles, nanoparticles are also synthetic polymeric drug carriers but are nanometer in size. Nanoparticles have mainly been tested in preclinical studies in rats and mice, and showed promise suppressing ocular angiogenesis by topical application (51,60).…”

Section: Micro-and Nanoparticlesmentioning

confidence: 99%

Targeting vascular endothelial growth factor using retinal gene therapy

2021

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Pharmacotherapies targeting vascular endothelial growth factor (VEGF) have revolutionized the management for neovascular retinal disorders including diabetic retinopathy and neovascular age-related macular degeneration. However, the burden of frequent injections, high cost, and treatment resistance in some patients remain unresolved. To overcome these challenges, newer generations of anti-angiogenic biological therapies, engineered proteins, implantable delivery systems, and biopolymers are currently being developed to enable more sustained, longer-lasting treatments. The use of gene therapies for pathologic angiogenesis has garnered renewed interests since the first FDA-approval of a gene therapy to treat inherited retinal diseases associated with biallelic RPE65 mutations. Newer generations of viral vectors and novel methods of intraocular injections helped overcome ocular barriers, improving the efficiency of transduction as well as safety profile. In addition, unlike current anti-VEGF gene therapy strategies which employ a biofactory approach to mimic existing pharmacotherapies, novel genome editing strategies that target proangiogenic factors at the DNA level offer a unique and distinct mechanistic approach that can potentially be more precise and lead to a permanent cure. Here, we review current anti-VEGF therapies and newer pharmacologic agents under development, examine technologies and progress in adapting anti-VEGF gene therapies, and explore the future application of CRISPR-Cas9 technology to suppress ocular angiogenesis.

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“…The addition of PEG on the surface of nanocarriers can avoid non-specific binding with blood components [ 78 ]. PEGylated BCZ-loaded serum albumin nanoparticles ( d = 301 ± 2 nm and ζ potential = −17 ± 1 mV) showed different characteristics compared to non-PEGylated nanoparticles ( d = 207 ± 2 nm and ζ potential = −26 ± 1 mV) [ 58 ]. Besides, the hydrophobicity of PEGylated nanoparticles was 1.5 times lower than that of non-PEGylated nanoparticles.…”

Section: Development Of Nanoparticulate Drug Delivery Systems For Bczmentioning

confidence: 99%

“…The subconjunctival injection of BCZ-loaded PLGA nanoparticles to mice almost completely inhibited corneal neovascularization after 14 days [ 45 ]. Non-PEGylated BCZ-loaded nanoparticles showed a higher antiangiogenic effect (2.4-fold) in rats than free BCZ, and lower values of cornea thickness (288 ± 85.6 µm) than PEGylated nanoparticles (431 ± 38.6 µm) [ 58 ]. In rabbits, BCZ-bearing dexamethasone-loaded PLGA nanoparticles showed a higher inhibitory effect in the neovascularization than free drugs [ 68 ].…”

Section: Pharmacological Applicationsmentioning

confidence: 99%

“…The antiangiogenic activity was maintained after encapsulation or surface conjugation of BCZ analyzed in vitro against cells lines [ 39 , 41 , 45 , 47 , 62 ] or in CAM model [ 55 , 61 , 66 , 68 ]. In animal models, BCZ encapsulated or surface conjugate demonstrated efficacy in the treatment of corneal neovascularization [ 45 , 58 ], choroidal neovascularization [ 68 ], antiangiogenic in a model of diabetes [ 54 ], non-small cell lung cancer [ 65 ], glioblastoma [ 48 ], melanoma [ 74 ], pancreatic adenocarcinoma combined with photodynamic therapy [ 40 ] and colorectal cancer [ 59 ].…”

Section: Limitations and Advantages Of Bcz Nanocarriersmentioning

confidence: 99%

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Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

et al. 2021

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Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance.

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In vivo effect of bevacizumab-loaded albumin nanoparticles in the treatment of corneal neovascularization

Cited by 41 publications

References 45 publications

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Targeting vascular endothelial growth factor using retinal gene therapy

Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications

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