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

Salma El-Sayed Radwan,1 Amal El-Kamel,1 Eiman I Zaki,2 Susi Burgalassi,3 Erica Zucchetti,3 Riham M El-Moslemany1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexand...

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Autores principales:	Radwan SES, El-Kamel A, Zaki EI, Burgalassi S, Zucchetti E, El-Moslemany RM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	retinopathy apatinib bovine serum albumin hyaluronic mucopenetration active targeting Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/67a945896ab24ceebf8226b2bda8145b
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spelling	oai:doaj.org-article:67a945896ab24ceebf8226b2bda8145b2021-12-02T16:51:47ZHyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy1178-2013https://doaj.org/article/67a945896ab24ceebf8226b2bda8145b2021-07-01T00:00:00Zhttps://www.dovepress.com/hyaluronic-coated-albumin-nanoparticles-for-the-non-invasive-delivery--peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Salma El-Sayed Radwan,1 Amal El-Kamel,1 Eiman I Zaki,2 Susi Burgalassi,3 Erica Zucchetti,3 Riham M El-Moslemany1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 3Department of Pharmacy, University of Pisa, Pisa, ItalyCorrespondence: Riham M El-Moslemany 1, Khartoum Square, Azarita, Alexandria, EgyptTel +11 201006020405Email riham.elmoslemany@alexu.edu.egPurpose: 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.Keywords: retinopathy, apatinib, bovine serum albumin, hyaluronic, mucopenetration, active targetingRadwan SESEl-Kamel AZaki EIBurgalassi SZucchetti EEl-Moslemany RMDove Medical Pressarticleretinopathyapatinibbovine serum albuminhyaluronicmucopenetrationactive targetingMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 4481-4494 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	retinopathy apatinib bovine serum albumin hyaluronic mucopenetration active targeting Medicine (General) R5-920
spellingShingle	retinopathy apatinib bovine serum albumin hyaluronic mucopenetration active targeting Medicine (General) R5-920 Radwan SES El-Kamel A Zaki EI Burgalassi S Zucchetti E El-Moslemany RM Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
description	Salma El-Sayed Radwan,1 Amal El-Kamel,1 Eiman I Zaki,2 Susi Burgalassi,3 Erica Zucchetti,3 Riham M El-Moslemany1 1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; 2Department of Histology and Cell Biology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 3Department of Pharmacy, University of Pisa, Pisa, ItalyCorrespondence: Riham M El-Moslemany 1, Khartoum Square, Azarita, Alexandria, EgyptTel +11 201006020405Email riham.elmoslemany@alexu.edu.egPurpose: 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.Keywords: retinopathy, apatinib, bovine serum albumin, hyaluronic, mucopenetration, active targeting
format	article
author	Radwan SES El-Kamel A Zaki EI Burgalassi S Zucchetti E El-Moslemany RM
author_facet	Radwan SES El-Kamel A Zaki EI Burgalassi S Zucchetti E El-Moslemany RM
author_sort	Radwan SES
title	Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
title_short	Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
title_full	Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
title_fullStr	Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
title_full_unstemmed	Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy
title_sort	hyaluronic-coated albumin nanoparticles for the non-invasive delivery of apatinib in diabetic retinopathy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/67a945896ab24ceebf8226b2bda8145b
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Hyaluronic-Coated Albumin Nanoparticles for the Non-Invasive Delivery of Apatinib in Diabetic Retinopathy

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