Multifunctional nano-in-micro delivery systems for targeted therapy in fundus neovascularization diseases

Abstract

Fundus neovascularization diseases are a series of blinding eye diseases that seriously impair vision worldwide. Currently, the means of treating these diseases in clinical practice are continuously evolving and have rapidly revolutionized treatment opinions. However, key issues such as inadequate treatment effectiveness, high rates of recurrence, and poor patient compliance still need to be urgently addressed. Multifunctional nanomedicine can specifically respond to both endogenous and exogenous microenvironments, effectively deliver drugs to specific targets and participate in activities such as biological imaging and the detection of small molecules. Nano-in-micro (NIM) delivery systems such as metal, metal oxide and up-conversion nanoparticles (NPs), quantum dots, and carbon materials, have shown certain advantages in overcoming the presence of physiological barriers within the eyeball and are widely used in the treatment of ophthalmic diseases. Few studies, however, have evaluated the efficacy of NIM delivery systems in treating fundus neovascular diseases (FNDs). The present study describes the main clinical treatment strategies and the adverse events associated with the treatment of FNDs with NIM delivery systems and summarizes the anatomical obstacles that must be overcome. In this review, we wish to highlight the principle of intraocular microenvironment normalization, aiming to provide a more rational approach for designing new NIM delivery systems to treat specific FNDs.

Keywords: Drug delivery; Fundus neovascular disease; Nano-in-micro (NIM) delivery system; Nanoparticles.

Fig. 1

Ocular therapeutics and NIM delivery strategies for FNDs

Fig. 2

The schematic illustration: (A) Physiological barriers in the eye. (B) Common methods of drug administration to the eyes

Fig. 3

Schematic depiction of hybrid cell membrane-coated biomimetic nanoparticles intended for non-invasive targeted therapy of laser-induced CNV. (A) Process of preparing [RBC-REC]NPs by encapsulating polymeric cores with integrated RBC-REC membranes. (B) Capture of proangiogenic factors by intravenous administration of [RBC-REC]NPs, inhibiting the effects of these factors on host neovascular endothelial cells

Fig. 4

A nanomicelle drug delivery system composed of copolymer EPC (nEPCs) carrying aflibercept for the treatment of FNDs. (A) Schematic diagram of aflibercept loaded nEPCs administratered ex vivo porcine eye were able to penetrate the cornea and effectively deliver a clinically relevant dose of aflibercept to the retinas with laser-induced choroidal neovascularization (CNV), resulting in regression of CNV. (B) Schematic diagram of biocompatibility of nEPCs in human cornea and RPE cell lines, in porcine corneal tissue, and in mice models. (C) Schematic diagram of the fluorescence leakage degree in choroidal lesion area and the staining of endothelial cells on the choroidal flat mounts

Fig. 5

An illustrated outline of the systemic, precise delivery of dendrimer triamcinolone acetonide (D-TA) to treat AMD. (A) Intravenously administered. D-TA was found to specifically target and transports D-TA to the crucial cells involved in the progression of AMD. (B) This targeted drug delivery approach could significantly reduce inflammation and choroidal neovascularization, ultimately decelerating the progression of the disease

Fig. 6

(A) Diagram illustrating the co-assembled components of MRP@DOX, designated as glycopeptide nanotransformers (GPNTs). (B) The operational steps of treatment

Fig. 7

Schematic illustration of the preparation of an NIM delivery system based on miRNA-223 and its use in gene therapy to regulate anti-inflammatory and anti-angiogenesis properties in patients with retinopathy of prematurity (ROP)