Nanocarrier mediated retinal drug delivery: overcoming ocular barriers to treat posterior eye diseases

Abstract

Effective drug delivery to the retina still remains a challenge due to ocular elimination mechanisms and complex barriers that selectively limit the entry of drugs into the eye. To overcome these barriers, frequent intravitreal injections are currently used to achieve high drug concentrations in vitreous and retina. However, these repetitive injections may result in several side effects. Recent advancements in the field of nanoparticle-based drug delivery could overcome some of these unmet needs and various preclinical studies conducted to date have demonstrated promising results of nanotherapies in the treatment of retinal diseases. Compared to the majority of commercially available ocular implants, the biodegradable nature of most nanoparticles (NPs) avoids the need for surgical implantation and removal after the release of the payload. In addition, the sustained drug release from NPs over an extended period of time reduces the need for frequent intravitreal injections and the risk of associated side effects. The nanometer size and highly modifiable surface properties make NPs excellent candidates for targeted ocular drug delivery. Studies have shown that nanocarriers enhance the intravitreal half-life and thus bioavailability of a number of drugs including proteins and peptides. In addition, they have shown promising results in delivering genetic material to the retinal tissues by protecting it from possible intravitreal degradation. This review covers the various challenges associated with drug delivery to the posterior segment of the eye, particularly the retina, and highlights the application of nanocarriers to overcome these challenges in context with recent advances in preclinical studies. WIREs Nanomed Nanobiotechnol 2018, 10:e1473. doi: 10.1002/wnan.1473 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

Polysaccharides in Ocular Drug Delivery

“…Even though intravitreal injections are generally safe, the monthly and bimonthly requirements for these injections in long-term treatment may cause problems such as infection and reduced patient compliance [128][129][130][131][132]. For these reasons, intravitreal drug delivery systems are needed that will maintain therapeutic drug concentrations for an extended time, prolong the drug effect, and reduce the required number of applications [128,130,131,[133][134][135]. Obviously, the systems must also be safe and ideally they must be biodegradable, as biodegradable drug delivery systems do not require subsequent surgery to remove them from the eye [133].…”

Association of the Somatostatin Analog Octreotide With Magnetic Nanoparticles for Intraocular Delivery: A Possible Approach for the Treatment of Diabetic Retinopathy

“…The use of nanoparticles as a drug delivery technology for the treatment of ocular diseases such as DR is receiving increasing attention (Amato et al, 2018b;Bisht et al, 2018;Jiang et al, 2018;Huang and Chau, 2019;Wong and Wong, 2019). The present study investigated the feasibility of using MNPs for the delivery of the somatostatin analog OCT to mammalian retinas.…”

Introductory Chapter: Current and Future Trends in the Diagnosis and Management of Uveitis

“…However, their intraocular bioavailability is limited by tear clearance, nasolacrimal drainage, and limited penetration related to the anterior biological barriers including the corneal epithelium and the hemato-aqueous barrier. Moreover, protein binding and enzymatic degradation also account for the limited absorption into target tissues [13]. Many different drug delivery strategies, including prodrugs, chemical permeability enhancers, stimuli-responsive in situ gels, and drug delivery carriers like liposomes are being developed to counter the elimination mechanisms mentioned before [14].…”