Differentially cleaving peptides as a strategy for controlled drug release in human retinal pigment epithelial cells

Casteleijn

Biochemistry and Biophysics Reports

et al. 2019

Self Cite

Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H 2 O 2 ) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells.

Section: Discussionmentioning

confidence: 99%

CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration

Casteleijn

Biochemistry and Biophysics Reports

et al. 2019

Self Cite

“…Particle stability in vitreous. Vitreous humor was isolated from porcine eyes [17,18] that were obtained from the local slaughterhouse in Finland and was used as the matrix to study stability of the polymeric micelles and polymersomes. Briefly, the porcine vitreous was mixed with polymersomes and polymer micelles at ratio of 1:1 and incubated at 37 • C. The samples at various time points were analyzed for hydrodynamic radius using asymmetric flow field-flow fractionation, multi-angle light scattering, and quasi elastic light scattering (AF4-MALS-QELS).…”

Section: Preparation and Physical Properties Of Self-assembling Nanoparticlesmentioning

confidence: 99%

Intravitreal Polymeric Nanocarriers with Long Ocular Retention and Targeted Delivery to the Retina and Optic Nerve Head Region

et al. 2021

Self Cite

Posterior eye tissues, such as retina, are affected in many serious eye diseases, but drug delivery to these targets is challenging due to various anatomical eye barriers. Intravitreal injections are widely used, but the intervals between invasive injections should be prolonged. We synthesized and characterized (1H NMR, gel permeation chromatography) block copolymers of poly(ethylene glycol), poly(caprolactone), and trimethylene carbonate. These polymers self-assembled to polymersomes and polymeric micelles. The mean diameters of polymersomes and polymeric micelles, about 100 nm and 30–50 nm, respectively, were obtained with dynamic light scattering. Based on single particle tracking and asymmetric flow field-flow fractionation, the polymeric micelles and polymersomes were stable and diffusible in the vitreous. The materials did not show cellular toxicity in cultured human umbilical vein endothelial cells in the Alamar Blue Assay. Pharmacokinetics of the intravitreal nanocarriers in the rabbits were evaluated using in vivo fluorophotometry. The half-lives of the polymersomes (100 nm) and the micelles (30 nm) were 11.4–32.7 days and 4.3–9.5 days. The intravitreal clearance values were 1.7–8.7 µL/h and 3.6–5.4 µL/h for polymersomes and polymeric micelles, respectively. Apparent volumes of distribution of the particles in the rabbit vitreous were 0.6–1.3 mL for polymeric micelles and 1.9–3.4 mL for polymersomes. Polymersomes were found in the vitreous for at least 92 days post-dosing. Furthermore, fundus imaging revealed that the polymersomes accumulated near the optic nerve and retained there even at 111 days post-injection. Polymersomes represent a promising technology for controlled and site-specific drug delivery in the posterior eye segment.

“…The presence of enzymes such as metalloproteinases, heparinase etc. could contribute in the polymeric degradation however sparse information is available on the elimination route of non-degradable implants [139][140][141][142]. Gels are used in drug delivery owing to their sustained drug release into the vitreous region.…”

Section: Nanomedicinementioning

confidence: 99%

Non-invasive multimodal imaging of Diabetic Retinopathy: A survey on treatment methods and Nanotheranostics

Sadasivam¹,

Gopinath²,

Shakya³

et al. 2021

Nanotheranostics

Diabetes Retinopathy (DR) is one of the most prominent microvascular complications of diabetes. It is one of the pre-eminent causes for vision impairment followed by blindness among the working-age population worldwide. The de facto cause for DR remains challenging, despite several efforts made to unveil the mechanism underlying the pathology of DR. There is quite less availability of the low cost pre-emptive theranostic imaging tools in terms of in-depth resolution, due to the multiple factors involved in the etiology of DR. This review work comprehensively explores the various reports and research works on all perspectives of diabetic retinopathy (DR), and its mechanism. It also discusses various advanced non-destructive imaging modalities, current, and future treatment approaches. Further, the application of various nanoparticle-based drug delivery strategies used for the treatment of DR are also discussed. In a nutshell, the present review work bolsters the pursuit of the development of an advanced non-invasive optical imaging modal with a nano-theranostic approach for the future diagnosis and treatment of DR and its associated ocular complications.