Abstract
Purpose :
To satisfy the demand for effective eye therapies, injectable hydrogels for controlled drug delivery are attractive. These materials have numerous of advantages including ease of application, precise delivery and the potential for prolonged duration between injections. To be effective, the gelation mechanism must result in the rapid gel formation with minimal drug loss. In this study, ophthalmic drug release from a novel aqueous driven PEG/Vitamin E hydrogel was examined. Gelation is triggered by the presence of water over broad range of temperature and pH and controlled and regulated by formulation composition.
Methods :
Polymerizable N-acryloyl-Vitamin E was synthesized and further copolymerized with methacrylate PEG to form a copolymer. NMR and GPC were used to confirm monomer structure, molecular weight and polymer composition. Formulations were prepared using different Vitamin E, PEG and copolymer contents. 10% (wt/wt) of model drugs including atropine, atropine monosulfate, dexamethasone and BR9910, a novel drug from Bayer GmbH, were loaded into these formulations and drug release examined. Drug only and formulation only samples were tested as controls. Gelation, injection and degradation properties were also investigated.
Results :
NMR confirmed the attachment of the methacrylate group to Vitamin E. Copolymers with molecular weights ranging from 10-56k and PEG/Vitamin E ratios between 1:0.5 – 1:3.9 were successfully prepared. Zero burst and controllable release were observed for the PEG/Vitamin E hydrogels. More polymer and more PEG in the formulations promoted a faster release, while the hydrogels with higher molecular weight copolymer and higher Vitamin E content led to slower release. Less hydrophobic drugs atropine monosulfate and atropine exhibited faster release which lasted only 6 hours and 24 hours respectively. Dexamethasone and the other hydrophobic drug showed a much slower release lasting over 3 months. Optimized formulations can be injected using a 30G needle.
Conclusions :
Model drugs were successfully released from these hydrogels. Burst release was avoided and drug release profiles could be regulated by tuning hydrogel recipes. Thus, controllable and sustained drug release can be achieved using this simple, responsive and safe approach to deliver ophthalmic drugs to back of the eye.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.