Synthesis and Characterisation of Photocrosslinked poly(ethylene glycol) diacrylate Implants for Sustained Ocular Drug Delivery

Abstract

PurposeTo investigate the sustained ocular delivery of small and large drug molecules from photocrosslinked poly(ethylene glycol) diacrylate (PEGDA) implants with varying pore forming agents.MethodsTriamcinolone acetonide and ovalbumin loaded photocrosslinked PEGDA implants, with or without pore-forming agents, were fabricated and characterised for chemical, mechanical, swelling, network parameters, as well as drug release and biocompatibility. HPLC-based analytical methods were employed for analysis of two molecules; ELISA was used to demonstrate bioactivity of ovalbumin.ResultsRegardless of PEGDA molecular weight or pore former composition all implants loaded with triamcinolone acetonide released significantly faster than those loaded with ovalbumin. Higher molecular weight PEGDA systems (700 Da) resulted in faster drug release of triamcinolone acetonide than their 250 Da counterpart. All ovalbumin released over the 56-day time period was found to be bioactive. Increasing PEGDA molecular weight resulted in increased system swelling, decreased crosslink density (Ve), increased polymer-water interaction parameter (χ), increased average molecular weight between crosslinks (Mc) and increased mesh size (ε). SEM studies showed the porosity of implants increased with increasing PEGDA molecular weight. Biocompatibility showed both PEGDA molecular weight implants were non-toxic when exposed to retinal epithelial cells over a 7-day period.ConclusionPhotocrosslinked PEGDA implant based systems are capable of controlled drug release of both small and large drug molecules through adaptations in the polymer system network. We are currently continuing evaluation of these systems as potential sustained drug delivery devices.

A Hydrogel Vitreous Substitute that Releases Antioxidant

“…The cells cultured in the hydrogel extracts were not statistically different than the control cells cultured in normal culture media. This result is unsurprising since PEGDA and PEGMA, being PEG derivatives, have been shown to be biocompatible in previous studies for ophthalmic applications . ARPE‐19 cells appeared to not be as sensitive to hydrogen peroxide as LECs.…”

“…The hydrogel stability study showed that PEGDA and PEGDA‐ co ‐PEGMA were stable and retained their solidity in enzymatic solutions at simulated physiological conditions (pH 7.4 and 37 °C) for at least 4 weeks (Figure ). Similarly, PEGDA implants were recently reported for sustained ocular drug delivery . These PEGDA implants, which were composed of the same components as our PEGDA hydrogel, swelled in water but did not dissolve.…”

A Non-Cytotoxic Resin for Micro-Stereolithography for Cell Cultures of HUVECs

“…The materials specifically chosen for this work have been investigated and used in biological applications outside the field of 3D printing previously. Low molecular weight acrylates such as PEGDA 250 and PEGDA 575 have been used for cultivating mammalian cells and in tissue engineering [22]. In another example, it has been shown that polymerized PEGDA has low binding toward proteins [23].…”

Additive Manufacturing of Personalized Pharmaceutical Dosage Forms via Stereolithography

“…Poly(ethylene glycol) (PEG) is a well-established synthetic polymeric material with PEG based hydrogels being well documented within the literature [29,[47][48][49][50] owing to the exceptional properties they afford, such as being nontoxic, biocompatible, and having notable tunability, in addition to being approved by the FDA for use in a variety clinical uses [51,52]. PEGDA has been shown to be a beneficial polymer in drug delivery applications and was investigated by McAvoy et al [53] to evaluate its potential to fabricate implants via UV polymerization in the release of both small and large drug molecules with the former being released at a greater rate than that of the latter. This indicates that by the careful selection of drugs it may be feasible to manipulate and control the rate at which they are released from the fabricated dosage form.…”