Utilization of Apatinib-Loaded Nanoparticles for the Treatment of Ocular Neovascularization

Halasz, Kathleen; Kelly, Shannon; Iqbal, Muhammad Tajwar; Pathak, Yashwant; Sutariya, Vijaykumar

doi:10.2174/1567201815666181017095708

Cited by 10 publications

(4 citation statements)

References 55 publications

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“…Apatinib, (Apa) a novel and selective inhibitor of VEGF receptor 2, has been demonstrated recently to exhibit anticancer efficacy by inhibiting the VEGF-signaling pathway. 21 , 22 Kim and Suh 23 investigated its antiangiogenic effect on oxygen-induced retinopathy. This was explained by its selective binding to VEGF receptor 2 that plays a crucial role in angiogenesis by stimulating auto-phosphorylation at the carboxy terminal tail and kinase-insert region, which is the most pro-angiogenic effect.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

Radwan¹,

El-Kamel²,

Zaki³

et al. 2021

IJN

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Purpose Apatinib (Apa) is a novel anti-vascular endothelial growth factor with the potential to treat diabetic retinopathy (DR); a serious condition leading to visual impairment and blindness. DR treatment relies on invasive techniques associated with various complications. Investigating topical routes for Apa delivery to the posterior eye segment is thus promising but also challenging due to ocular barriers. Hence, the study objective was to develop Apa-loaded bovine serum albumin nanoparticles (Apa-BSA-NPs) coated with hyaluronic acid (HA); a natural polymer possessing unique mucoadhesive and viscoelastic features with the capacity to actively target CD44 positive retinal cells, for topical administration in DR. Methods Apa-BSA-NPs were prepared by desolvation using glutaraldehyde for cross-linking. HA-coated BSA-NPs were also prepared and HA: NPs ratio optimized. Nanoparticles were characterized for colloidal properties, entrapment efficiency (EE%), in vitro drug release and mucoadhesive potential. In vitro cytotoxicity on rabbit corneal epithelial cells (RCE) was assessed using MTT assay, while efficacy was evaluated in vivo in a diabetic rat model by histopathological examination of the retina by light and transmission electron microscopy. Retinal accumulation of fluorescently labeled BSA-NP and HA-BSA-NP was assessed using confocal microscope scanning. Results Apa-HA-BSA-NPs prepared under optimal conditions showed size, PdI and zeta potential: 222.2±3.56 nm, 0.221±0.02 and −37.3±1.8 mV, respectively. High EE% (69±1%), biphasic sustained release profile with an initial burst effect and mucoadhesion was attained. No evidence of cytotoxicity was observed on RCE cells. In vivo histopathological studies on DR rat model revealed alleviated retinal micro- and ultrastructural changes in the topical HA-Apa-BSA-NP treated eyes with normal basement membrane and retinal thickness comparable to normal control and intravitreally injected nanoparticles. Improved retinal accumulation for HA-BSA-NP was also observed by confocal microscopy. Conclusion Findings present HA-Apa-BSA-NPs as a platform for enhanced topical therapy of DR overcoming the devastating ocular complications of the intravitreal route.

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Section: Introductionmentioning

confidence: 99%

Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

Radwan¹,

El-Kamel²,

Zaki³

et al. 2021

IJN

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“…For the treatment of diabetic retinopathy, one study created topical delivery of hyaluronic acid (HA) NPs loaded with apatinibc (Apa) to obtain better delivery to retinal cells [48]. Apa, a brand-new VEGF receptor 2 selective inhibitor, has recently been demonstrated to have anticancer properties by blocking the VEGF signaling pathway [49]. HA is a biodegradable, nonimmunogenic biopolymer with the ability to interact with multiple retinal cell surface differentiation (CD44) receptor clusters [50].…”

Section: Nps For Treatment Of Retinal Diseasesmentioning

confidence: 99%

Exploration: Nanoparticles in the Diagnosis and Treatment of Retinal Diseases

Wang

Xie

Chen

et al. 2023

Journal of Nanomaterials

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In recent years, research on nanoparticles (NPs) has brought a new phase in the development of medicine. The term “NPs” refers to nanoscale particles, typically between 10 and 1,000 nm in size, that are within the range of cellular and molecular structures. Compared with traditional ophthalmic drugs, NPs can carry drugs to overcome obstacles, target drug delivery, prolong drug release, reduce drug toxicity, and can be used in gene therapy. After a brief introduction to the classification of NPs, we will focus on the potential applications of different NPs in the diagnosis and treatment of different retinal diseases and introduce innovative methods derived from NPs.

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“…13,15,21 The physical state of drug molecule in NPs affects their release and solubility in external medium and so DSC thermograms is helpful in identifying the nature or physical state of the drug alone and while being loaded in NPs. 22 AX showed sharp endothermic peak at around 212°C indicating its specific melting point. This endothermic peak was not present in DSC spectra of AX-NPs approving the complete loading of AX in NPs and confirming amorphous form of loaded AX.…”

Section: Differential Scanning Calorimetrymentioning

confidence: 99%

“…However, in case of nanoparticle formulation, there was an initial low level of VEGF control, which at later time points became stronger as the drug released from the matrix over a longer duration. 22,29 Therefore, sustained inhibitory effect of nanoparticle formulation as compared with drug solution was observed.…”

Section: Anti-vegf Elisamentioning

confidence: 99%

Axitinib-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Age-Related Macular Degeneration: Formulation Development andIn VitroCharacterization

Narvekar

Bhatt

Fnu

et al. 2019

ASSAY and Drug Development Technologies

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Despite all the research aiming to treat ocular diseases, agerelated macular degeneration (AMD) remains one of the serious diseases worldwide, which needs to be treated. Neovascularization is a key factor in AMD and thus antiangiogenic therapy is beneficial in reducing the development of new abnormal blood vessels. Axitinib, multireceptor tyrosine kinase inhibitor, is a small molecule that works by blocking vascular endothelial growth factor receptors (VEGFR) and platelet-derived growth factor receptors (PDGFR) responsible for developing neovascularization. The goal of this study is to develop a sustained release formulation of axitinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles to minimize frequent administration of the drug by intravitreal injection. The nanoparticles were characterized for particle size and zeta potential, as well as using differential scanning calorimetry, transmission electrode microscope, and in vitro drug release profile. The cytotoxicity of the formulation was evaluated on human retinal pigmented epithelium ARPE19 cells by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt] assay. The cellular uptake, antimigration assay, and vascular endothelial growth factor (VEGF) expression levels were found out in vitro using cells. The optimized formulation was 131.33 -31.20 nm in size with -4.63 -0.76 mV zeta potential. Entrapment efficiency was found to be 87.9% -2.7%. The cytotoxicity of ARPE19 cells was <12% for nanoparticles suggesting the in vitro compatibility at 10 lM concentration of drug. Cellular uptake, antimigration assay, and VEGF expression levels for the nanoparticles suggested greater uptake, significant antiangiogenic potential, and inhibition of VEGF activity. The results showed successful development of axitinib-loaded PLGA nanoparticles as an alternative potential treatment for AMD.

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Utilization of Apatinib-Loaded Nanoparticles for the Treatment of Ocular Neovascularization

Cited by 10 publications

References 55 publications

Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

Exploration: Nanoparticles in the Diagnosis and Treatment of Retinal Diseases

Axitinib-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles for Age-Related Macular Degeneration: Formulation Development andIn VitroCharacterization

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