Hyaluronic acid‐based nanocomposite hydrogels for ocular drug delivery applications

Abstract

Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic applications owing to its unique properties of biocompatibility, biodegradation, and viscoelasticity. HA being a natural component of eye tissue with significant role in wound healing is a natural choice as a carrier for ocular drug delivery, provided the incorporated drugs are released in a sustained manner. However, localized sustained release of drugs inside eye has been difficult to achieve because of the inability to retain carriers for long periods in the eye. Using noncrosslinked (soluble) HA offers limited control over site retention of drugs. In order to obtain prolonged sustained delivery, two HA-based composite hydrogels incorporating nanocarriers, have been synthesized and characterized for swelling, rheology, degradation, and in vitro release of latanoprost, a drug used to reduce intraocular pressure. The HA is first chemically modified, mixed with drug-loaded liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro release study shows longer sustained release of latanoprost from composite hydrogels as compared to liposomes or hydrogels alone indicating additional resistance to drug diffusion because of the incorporation of liposomes inside the hydrogels. It is believed that these nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases.

Hydrogel Biomaterials for Application in Ocular Drug Delivery

“…Hydrogels are able to be utilized in conjunction with other technologies in order to improve ocular drug delivery. This can be seen in a study by Widjaja et al (2015), where a hyaluronic acid-nanocomposite hydrogel was formulated with a sample drug, latanoprost. This system, in which the modified hyaluronic acid was combined with liposomes which contained the drug before crosslinking occurred, showed longer drug release profiles than the hydrogel and liposomes each did on their own.…”

“…The drug release mechanism is shown in Figure 5; it was found that both liposomes with entrapped drug and free drug were released from the hydrogel matrix which is what is believed to be the reason behind the sustained drug delivery profile which was observed. Although only preliminary studies were conducted; with further research, these nanocomposite systems are a potential candidate for the delivery of drugs to the eye after a single administration (Widjaja et al, 2015). Figure 5 shows how the drug is released from the system.…”

“…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).…”

Microparticulated systems based on chitosan and poly(vinyl alcohol) with potential ophthalmic applications

“…Synthetic polymers (polyvinyl alcohol, poloxamers, etc.) and polysaccharides (chitosan, hyaluronic acid, methylcellulose, carboxymethylcellulose, dextran, gellan) are frequently used to obtain ophthalmic drug delivery systems (Patel et al, 2010a;Kadajji and Betageri, 2011;Hermans et al, 2014;Widjaja et al, 2014). If these polymers are mucoadhesive, i.e.…”

Development and in vitro/in vivo Evaluation of Liposomal Gels for the Sustained Ocular Delivery of Latanoprost

“…Latanoprost acid experiences a higher penetration resistance through the lipophilic epithelium and the endothelial cells of the corneal membrane [2,15]. Despite the popularity of latanoprost in the management of glaucoma, a careful literature review revealed only handful studies reporting on the development of sustained release delivery systems [1,2,[16][17][18][19]. Most of these studies used subconjunctival injection of latanoprost liposomes, which prolonged the drug release for up to 120 days.…”