Advanced drug delivery and targeting technologies for the ocular diseases

Abstract

Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies need to be further advanced to get better compliance and higher clinical impacts. Conclusion: Despite mankind successful battle on ocular diseases, our challenge will continue to battle the ocular disease that happen with aging. Yet, we need to understand the molecular aspects of eye diseases in a holistic way and develop ultimate treatment protocols preferably as non-invasive systems.

Functional intercalated nanocomposites with chitosan-glutathione-glycylsarcosine and layered double hydroxides for topical ocular drug delivery

“…The chemical structures of CG-GS and intermediates were characterized by 1 H NMR, as shown in Figure 1. The peaks at chemical shifts 3.5-4.5, 3.0 and 2.0 ppm were ascribed to the H2, H3-H6 and acetyl protons in the CTS skeleton (Figure 1h), respectively.…”

“…[1][2][3][4][5] However, topical administration remains the most preferred route of ocular drug delivery, because it is noninvasive, painless and convenient. 6 Topically applied drug/formulation may not only reach anterior tissues but also reach back-of-the-eye tissues.…”

“…[8][9][10] Increasing the retention time in the precorneal area and improving the permeability across ocular tissues of drugs are two major key aspects to enhance ocular bioavailability. 1 Ban et al developed positively charged chitosan (CTS)-coated solid lipid nanoparticles with high ocular bioavailability, which was ascribed to the electrostatic interaction between the positively charged nanoparticles and the negatively charged ocular surface. 11 Furthermore, CTS derivatives, especially thiolated CTS, with good mucoadhesivity and enhanced trans-cornea drug penetration have been widely used in topical ocular drug delivery.…”

Emerging Trends in Ocular Drug Delivery: A Review on Recent Updates

“…Because frequent samplings of drug from eye chambers is very dangerous and usually not recommended. Especially, the aqueous and vitreous humor are not good places to collect samples from [6]. Hence, most of the studies are conducted in small animals and correlated to humans.…”

“…Blood-aqueous barrier in anterior segment of the eye, and blood vessels in iris body have tight junctions which prevent free distribution of molecules in between anterior and posterior chambers. Because of these and other complex structure limitations, drug molecules cannot pass to the posterior chamber from anterior chambers [6]. However, the formulation/compound will not be completely or significantly absorbed into the intraocular tissues due to the rapid pre-corneal mechanisms.…”