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Review
. 2020 Mar 20:8:228.
doi: 10.3389/fbioe.2020.00228. eCollection 2020.

Hydrogel Biomaterials for Application in Ocular Drug Delivery

Courtney R Lynch  1 , Pierre P D Kondiah  1 , Yahya E Choonara  1 , Lisa C du Toit  1 , Naseer Ally  2 , Viness Pillay  1
Affiliations
Review

Hydrogel Biomaterials for Application in Ocular Drug Delivery

Courtney R Lynch et al. Front Bioeng Biotechnol. .

Abstract

There are many challenges involved in ocular drug delivery. These are a result of the many tissue barriers and defense mechanisms that are present with the eye; such as the cornea, conjunctiva, the blinking reflex, and nasolacrimal drainage system. This leads to many of the conventional ophthalmic preparations, such as eye drops, having low bioavailability profiles, rapid removal from the administration site, and thus ineffective delivery of drugs. Hydrogels have been investigated as a delivery system which is able to overcome some of these challenges. These have been formulated as standalone systems or with the incorporation of other technologies such as nanoparticles. Hydrogels are able to be formulated in such a way that they are able to change from a liquid to gel as a response to a stimulus; known as "smart" or stimuli-responsive biotechnology platforms. Various different stimuli-responsive hydrogel systems are discussed in this article. Hydrogel drug delivery systems are able to be formulated from both synthetic and natural polymers, known as biopolymers. This review focuses on the formulations which incorporate biopolymers. These polymers have a number of benefits such as the fact that they are biodegradable, biocompatible, and non-cytotoxic. The biocompatibility of the polymers is essential for ocular drug delivery systems because the eye is an extremely sensitive organ which is known as an immune privileged site.

Keywords: biomaterials; biopolymers; hydrogel; nanotechnology; ocular drug delivery; safety by design.

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Figures

FIGURE 1
FIGURE 1
Highlighting the potential application for hydrogels in ocular drug delivery. These include the delivery of drugs to both the anterior and posterior segments of the eye which will aid in overcoming the physiological barriers. Possible topical formulations for delivery to the anterior segment include systems which gel upon application (in situ gelling formulations) and contact lenses. Posterior segment formulations include intravitreal injections, which are made more effective by hydrogel technology, and cell carrier systems (adapted with permission from Kirchhof et al., 2015).
FIGURE 2
FIGURE 2
Illustration of the blood–ocular barriers which inhibit the movement of active ingredients into the eye from systemic circulation; namely, the blood–aqueous barrier and the blood–retinal barrier. These barriers result in the need for high systemic dosages of drugs in order to achieve an adequate concentration within the intended tissues. This high dosage can lead to unwanted side effects (adapted with permission from Occhiutto et al., 2012).
FIGURE 3
FIGURE 3
Illustration of the chemical and physical stimuli to which a hydrogel can respond. These stimuli are able to be provided by the body (for example, temperature and/or pH changes between conditions under which the hydrogels are stored and the conditions of the site into which it is administered) or externally (for example, ultrasound waves or a magnetic field). These stimuli can cause or a hydrogel to swell or de-swell, depending on how the formulation is designed. Reversible hydrogels are able to return to their original state when the stimulus is removed (adapted with permission from Fathi et al., 2015).
FIGURE 4
FIGURE 4
Chemical structures of each of the biopolymers; chitosan, hyaluronic acid, gelatin, alginate, methylcellulose, and collagen, for ocular polymeric drug delivery.
FIGURE 5
FIGURE 5
Drug release mechanism from hyaluronic acid-based nanocomposite hydrogel system. The active ingredient is loaded within the liposomes which are in turn loaded into the hydrogel. The drug is then released from the liposomes and diffuses through the hydrogel. It was also found that liposomes themselves were able to be released from the hydrogel. Both of these release mechanisms resulted in the sustained drug release seen in the formulation. This figure also highlights how the liposomes were incorporated into the hydrogel before it was cross-linked (adapted with permission from Widjaja et al., 2015).
FIGURE 6
FIGURE 6
Illustration of the double crosslinking method using β-glycerophosphate disodium and genipin. The β-glycerophosphate disodium negatively charged phosphate groups underwent electrostatic attraction to the positively charged chitosan which gave this formulation the ability to transition between a solution and a gel (adapted with permission from Song et al., 2018).
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References

    1. Agrawal A. K., Das M., Jain S. (2010). In situ systems as “smart” carriers for sustained ocular drug delivery. Exp. Opin. Drug Deliv. 9 383–402. 10.1517/17425247.2012.665367 - DOI - PubMed
    1. Al Khateb K., Ozhmukhametova E. K., Mussin M. N., Seilkhanov S. K., Rakhypbekov T. K., Lau W. M., et al. (2016). In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery. Int. J. Pharm. 502 70–79. 10.1016/j.ijpharm.2016.02.027 - DOI - PubMed
    1. Ameeduzzafar J. A., Ali J., Fazil M., Qumbar M., Khan N., Ali A. (2016). Colloidal drug delivery system: amplify the ocular delivery. Drug Deliv. 23 700–716. 10.3109/10717544.2014.923065 - DOI - PubMed
    1. Attama A., Reichi S., Muller-Goymann C. C. (2008). Diclofenac sodium delivery to the eye: In vitro evaluation of novel solid lipid nanoparticle formulation using human cornea construct. Int. J. Pharm. 355 307–313. 10.1016/j.ijpharm.2007.12.007 - DOI - PubMed
    1. Bain M. K., Bhowmik M., Ghosh S. H., Chattopadhyay D. (2009). In situ fast gelling formulation of methyl cellulose for in vitro ophthalmic controlled delivery of ketorolac tromethamine. J. Appl. Polymer Sci. 113 1241–1246. 10.1002/app.30040 - DOI

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