An Anti‐angiogenic Reverse Thermal Gel as a Drug‐Delivery System for Age‐Related Wet Macular Degeneration

Abstract

Reverse thermal gels have numerous biomedical implications, as they undergo physical gelation upon temperature increases and can incorporate biomolecules to promote tissue repair. Such a material is developed for the sustained release of bevacizumab (Avastin), a drug used to treat age-related macular degeneration. The polymer, poly(ethylene glycol)-poly-(serinol hexamethylene urethane) (ESHU), forms a physical gel when heated to 37 °C and shows good cytocompatibility with ocular cells. ESHU is capable of sustaining bevacizumab release over 17 weeks in vitro, and the release kinetics can be altered by changing the drug dose and the ESHU concentration. These results suggest that ESHU is biologically safe, and suitable for ocular drug delivery.

Injectable Chemically Crosslinked Hydrogel for the Controlled Release of Bevacizumab in Vitreous: A 6-Month In Vivo Study

“…17 Among these approaches, in situ hydrogels have gained increasing attention in the recent 2 years because of the mild encapsulation condition and the hydrophilic nature of the network. [18][19][20][21][22][23] Different from our approach of using chemically crosslinked polymer-polymer in situ gel, a majority of other studies utilized physically crosslinked thermosensitive hydrogels as the controlled release vehicles. However, although promising in vitro protein release has been demonstrated by this approach, 19,21 the in vivo performance was not satisfactory and has only been demonstrated in one study.…”

“…[18][19][20][21][22][23] Different from our approach of using chemically crosslinked polymer-polymer in situ gel, a majority of other studies utilized physically crosslinked thermosensitive hydrogels as the controlled release vehicles. However, although promising in vitro protein release has been demonstrated by this approach, 19,21 the in vivo performance was not satisfactory and has only been demonstrated in one study. 22 Moreover, hydrophobic interaction between protein and the polymer may potentially affect the chemical or physical stability of the protein.…”

Biocompatible Reverse Thermal Gel Sustains the Release of Intravitreal Bevacizumab In Vivo

“…19 Cells were suspended in Dulbecco's modified Eagle's medium (DMEM; Invitrogen) supplemented with 10% fetal bovine serum (Hyclone, Logan, UT), penicillin/streptomycin, gentamicin, and amphotericin B, then incubated at 378C in 5% CO 2 until cells were 90% confluent. For in vitro cytotoxicity assays, cells were exposed to one of four experimental conditions: serum-free media (control), 15% wt/vol ESHU in DMEM, perfluorooctane (PFO), or 5000 cs silicone oil.…”

“…18,19 To prepare bevacizumab-loaded ESHU, the desired amount of polymer was measured out and sterilized via ethylene oxide (12-hour cycle, 208C, >35% relative humidity). The sterilized ESHU polymer then was dissolved in a solution of 25 mg/mL bevacizumab, or PBS for control gels, at 48C in the dark at a polymer concentration of 15% wt/vol.…”

“…18 We hypothesized that ESHU would be a suitable platform for intraocular drug delivery and demonstrated that it is compatible with cells from ocular sources, and capable of releasing bevacizumab over a 17-week period in vitro. 19 The aim of the present study was to demonstrate sustained bevacizumab release in vivo when compared to a standard, bolus injection. Additionally, we compared the cytocompatibility of ESHU to other commonly-used ocular biomaterials and assessed the in vivo biocompatibility of the gel.…”