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

Abstract

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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“…Moreover, polysaccharides can play a role in increasing the corneal residence time of the topically instilled drugs. Specifically, the bioadhesive properties of HA as well as its interaction with its receptors on the corneal epithelium may result in a prolonged precorneal-retention, as already reported in previous works [58,59]. To assess the bioadhesive properties of HA-CH NHs, both, ex vivo studies by fluorescence microscopy and in-tube analyses with mucin were performed (Figure 3A-E).…”

CuS@BSA-NB2 Nanoparticles for HER2-Targeted Photothermal Therapy

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Nano-Biomaterials for Retinal Regeneration

“…Furthermore, hybrid nanostructures penetrate deeper inside the ocular segments, resulting in the localized delivery of drugs at high dosages, enriching the local drug concentration. Recently, a few studies have shown that nanoparticlebased eye drop formulations can deliver apatinib and triamcinolone acetonide to the rat retina [152,153]. Therefore, improvement of the noninvasive infiltration of nanomaterials through the blood-retinal barrier will be a stepping stone in the field of biomedicine.…”