Hydrogel-based ocular drug delivery systems: Emerging fabrication strategies, applications, and bench-to-bedside manufacturing considerations

Abstract

The physiological barriers of the eye pose challenges to the delivery of the array of therapeutics for ocular diseases. Hydrogels have been widely explored for medical applications and introduce possible solutions to overcoming the medication challenges of the ocular environment. While the innovations in drug encapsulation and release mechanisms, biocompatibility, and treatment duration have become highly sophisticated, the challenge of widespread application of hydrogel formulations in the clinic is still apparent. This article reviews the latest hydrogel formulations and their associated chemistries for use in ocular therapies, spanning from external anterior to internal posterior regions of the eye in order to evaluate the state of recent research. This article discusses the utility of hydrogels in soft contact lens, wound dressings, intraocular lens, vitreous substitutes, vitreous drug release hydrogels, and cell-based therapies for regeneration. Additional focus is placed on the pre-formulation, formulation, and manufacturing considerations of the hydrogels based on individual components (polymer chains, linkers, and therapeutics), final hydrogel product, and required preparations for clinical/commercial applications, respectively.

Keywords: Drug delivery; Hydrogel; Injectable; Sterilization; Topical.

Figure 1

Regions of the eye where hydrogels are currently used. Reprinted with permission from (Kirchhof et al., 2015). Copyright 2015 Elsevier Inc.

Figure 2

Examples of physical and chemical hydrogel formation. Reprinted with permission from (Ghobril and Grinstaff, 2015). Copyright 2015 The Royal Society of Chemistry.

Figure 3

Sterilization and disinfection methods during hydrogel manufacturing. Reprinted with permission from (Galante et al., 2018). Copyright 2017 Wiley Periodicals, Inc.

Figure 4

Hybrid dendrimer/PLGA hydrogel for the codelivery of brimonidine and timolol maleate Reprinted with permission from (Yang et al., 2012). Copyright 2012 American Chemical Society.

Figure 5

Chemical structures of the individual components of DuraSealTM hydrogel, (A) trilysine crosslinker and (B) tetrafunctional PEG capped with N-Hydroxysuccinimide. Reprinted with permission from (Ghobril and Grinstaff, 2015). Copyright 2015 The Royal Society of Chemistry.

Figure 6

Diagram of drug eluting IOL by incorporating drug-loaded poly(L-lactide-co-ɛ-caprolactone) (PLC) polymer depot between the IOL and haptic (Tan et al., 2016).

Figure 7

Schematic of injectable dendrimer hydrogel. Drug molecule is added during the gelation process between alkyne and azide groups. Reprinted with permission from (Xu et al., 2017). Copyright 2017 American Chemical Society.