A biocompatible reverse thermoresponsive polymer for ocular drug delivery

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss, the treatment of which may require monthly intravitreal injections. This is a burden on patients and health services, and new delivery modalities that reduce injection frequency are required. To that end, we investigated the suitability of a novel reverse thermoresponsive polymer (RTP) as an ocular drug-delivery vehicle. In this work, we detail the structure and synthesis of a novel RTP, and determine drug release curves for two drugs commonly used in the treatment of AMD, bevacizumab and aflibercept. Biocompatibility of the RTP was assessed in vitro in human and rat cell lines and in vivo following intravitreal injection in rats. Bevacizumab demonstrated a more appropriate release profile than aflibercept, with 67% released within 14 days and 78% released in total over a 183-day period. No toxic effects of RTP were seen in human or rat cells in up to 14 days of co-culture with RTP. Following intravitreal injection, intraocular pressure was unaffected by the presence of RTP and no changes in retinal function or structure were observed at 1 week or 1 month post-injection. RTP injection did not cause inflammation, gliosis or apoptosis in the retina. This work demonstrates the potential suitability of the novel RTP as a sustained-release vehicle for ocular drug delivery for anti-neovascular therapies. Optimization of polymer chemistry for optimal drug loading and release is needed.

Advancing the stimuli response of polymer-based drug delivery systems for ocular disease treatment

“…In another study, a thermo-responsive polymer, prepared via functionalization of PEG with polyester polyol (PP), was able to provide a sustained release profile of bevacizumab for over 183 days. 125 The PEG/PP thermo-responsive polymer solution did not exhibit toxic effects in human and rat cells in vitro. Also, at 1-month post-injection, no changes in IOP, and no alterations in the retinal function and structure were observed.…”

Considerations for Polymers Used in Ocular Drug Delivery

“…To overcome these challenges, significant effort has been invested in the development of intravitreal drug delivery systems. Recent examples include a thermoresponsive polymer made of a combination of pentaerythritol, lactic acid, and ε-caprolactone functionalized with PEG and another thermoresponsive hydrogel made of PEG-poly(serinol hexamethylene urethane), which can be injected into the intraocular space to serve as a controlled-release system for extended drug delivery (226,228). Researchers have also investigated a variety of polymer nanoparticles, using materials such as PCL and PLGA to develop drug-loaded nanoparticles for intravitreal injection (226,227).…”

Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update

“…Among these, hydrogels have obtained considerable attention because of their versatile features [ 121 , 122 ]. These polymeric materials could absorb high quantities of water and have the ability to modify their physical characteristics, e. g. transitioning from solution-to-gel, or gel-to-solution, in response to external stimuli, for example, temperature, pH, magnetic field, and ionic strength [ 123 , 124 ]. In the following, two classes of polymeric-based materials for the treatment of ocular diseases will be discussed.…”