Potential Drug Delivery Approaches for XFS-associated and XFS-associated Glaucoma

Abstract

Key tissue targets in treating exfoliation syndrome (XFS) and the associated glaucoma include lens, iris, and ciliary body, which produce the exfoliative material, and the trabecular meshwork, which may be impaired by the exfoliative material. In addition to antiglaucoma drug therapy, strategies for treating the disease include approaches for preventing formation of exfoliative material as well as those aimed at digesting exfoliative material. A variety of drug molecules including small molecules, protein drugs, and nucleic acids are potential candidates for treating XFS. Potential drug classes include antioxidants, lysyl oxidase-like 1 enhancers, antifibrotics, anti-inflammatory agents, proteases, and chaperones. However, the delivery of these agents to the target tissues in the anterior segment is hindered by protective static and dynamic barriers of the eye. Thus, unique drug delivery approaches are needed for each drug type (small molecules, proteins, and nucleic acids). In addition, there is a need for sustaining drug therapy for treating XFS, which can potentially be addressed by using nanoparticles, microparticles, implants, and contact lens delivery systems. This article provides an overview of drug delivery challenges and opportunities in treating XFS with the focus being on nanomedicines.

Attenuation of experimental autoimmune neuritis with locally administered lovastatin‐encapsulating poly(lactic‐co‐glycolic) acid nanoparticles

“…PLGA nanoparticles are ideal biodegradable candidates with which to efficiently encapsulate hydrophobic compounds for controlled and sustained release (Astete and Sabliov ; Kulkarni and Kompella ). Previous studies from our laboratory have shown that a short‐term high‐dose course of intraperitoneally administered statins markedly restricts the transendothelial trafficking of autoreactive leukocytes into peripheral nerves of adult male Lewis rats and safely attenuates the development and progression of EAN.…”

“…Here, we report that a one-time localized perineural application of lovastatin-encapsulating PLGA nanoparticles significantly attenuates the clinical development of systemic experimental autoimmune neuritis (EAN), a well-established animal model of AIDP/GBS. PLGA nanoparticles are ideal biodegradable candidates with which to efficiently encapsulate hydrophobic compounds for controlled and sustained release (Astete and Kulkarni and Kompella 2014). Previous studies from our laboratory have shown that a short-term high-dose course of intraperitoneally administered statins markedly restricts the transendothelial trafficking of autoreactive leukocytes into peripheral nerves of adult male Lewis rats and safely attenuates the development and progression of EAN.…”

“…; Sirtori ). Poly(lactic‐co‐glycolic) acid (PLGA) nanoparticles are ideal biodegradable candidates which efficiently encapsulate hydrophobic compounds for controlled and sustained release (Astete and Sabliov ; Kulkarni and Kompella ). Local administration of statin‐encapsulating PLGA nanoparticles accelerates healing in pre‐clinical bone fracture models by increasing transcription of BMP‐2 at the site of injury (Garrett et al .…”

“…Nanotechnology-based drug delivery represents a relatively new and innovative approach by which to administer therapeutic compounds exhibiting low bioavailability, high systemic toxicity, and/or poor water solubility, including statins (Wischke and Schwendeman 2008;Romana et al 2014;Sirtori 2014). Poly(lactic-co-glycolic) acid (PLGA) nanoparticles are ideal biodegradable candidates which efficiently encapsulate hydrophobic compounds for controlled and sustained release (Astete and Sabliov 2006;Kulkarni and Kompella 2014). Local administration of statin-encapsulating PLGA nanoparticles accelerates healing in pre-clinical bone fracture models by increasing transcription of BMP-2 at the site of injury (Garrett et al 2007;Ho et al 2011).…”

Nanotechnology Applications for Glaucoma

“…This form of treatment could use several proposed disease-specific molecules as therapeutic agents, including antioxidants (superoxide dismutase, catalase, curcumin), LOXL1 enhancers (polypeptides and nucleic acids), anti-inflammatory agents, antiaggregation agents (chaperones such as clusterin and crystallins), small molecule chaperones, and proteases (MMP-2 and MMP-9). 57,58 As suggested by Kulkarni et al, 58 therapeutic agents could be delivered to the anterior capsule in a targeted way and designed to be uptaken rapidly and released in a controlled manner by using nanosystems. Similarly, we recently suggested the selection of tissuespecific peptides either to dissolve the fibrillar structures or to be used as drug-targeting molecules.…”