A drug delivery approach for a thermoresponsive polymer shows sustained anti-VEGF treatment for AMD

Researchers in an independent Australian federal research agency (CSIRO), Victoria, Australia, have demonstrated that a novel polymer synthesizing two anti-VEGF treatments (bevacizumab and aflibercept) may be used to extend drug delivery release profiles over a 183 day period.  As anti-VEGF intravitreal injections generally require burdensome monthly treatments, the new reverse thermoresponsive polymer (RTP) may significantly benefit patients in minimizing the number of clinical visits needed.  While currently pre-clinical work is focused in cell and animal models to date, the Australian researchers hope that future human clinical studies will use sustained release treatments for several indications, including AMD and diabetic macular edema.


At present, anti-VEGF treatments for patients can require continual intravitreal injections for up to approx. 12 clinical visits per year.  This can impact both patient and clinician, in addition to increase significant supports for administration, transport, time and costs.  To improve such care, researchers have now aimed to prepare in-vitro release kinetics for both bevacizumab and aflibercept.  The new thermoresponsive polymer has developed a 30% concentration and 1.8% drug content of the anti-VEGF agents. According to the researchers, both bevacizumab (Genentech) and aflibercept (Regeneron) have a similar release mechanisms comprising of two phases of release: an initial diffusion-controlled phase where the loosely bound drug diffuses from a polymer gel, followed then by a degradation-controlled release phase as the polymer degrades.  Studies of the pre-clinical research showed that bevacizumab has a higher burst release during the initial 14 day diffusion period. The initial burst release was 67% of bevacizumab during the first 14 days, as compared to 10% release of aflibercept for the same time period.  Thereafter, it was estimated that approximately 95% of bevacizumab and 25% of aflibercept was released over the 183-day period.  In addition, the studies indicated that there were no adverse effects to the polymer on cell viability in human and animal cell lines and no evidence of associated inflammation or elevated intraocular pressure.


In conclusion of the studies, the researchers stated, “the drug and vehicle can be mixed at room temperature and injected in liquid form into the eye, using conventional intravitreal injection technique, where they combine to form a gel capable of delayed anti-VEGF drug release”. The research team also confirmed that the work “serves as the basis for further studies to explore the use of thermoresponsive polymers in the treatment of people with ocular disorders such as AMD and diabetic macular edema who require ongoing anti-VEGF therapy”.