Purchase this article with an account.
Britta Rauck, Carlos Medina-Mendez, Thomas Friberg, Yadong Wang; Characterization of the In Vitro Release Kinetics of Bevacizumab from a Biocompatible Reverse Thermal Gel. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3209.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
A biodegradable, biocompatible reverse thermal gel demonstrates excellent promise as an intraocular drug delivery system as it is minimally invasive and can sustain the release of drugs substantially. In order to maximize the release profile, we loaded several doses of bevacizumab (Avastin) using multiple gel concentrations and studied the release behavior in vitro. Moreover, we confirmed the ability of the release system to maintain the bioactivity of the released drug.
We synthesized poly(ethylene glycol)-poly(serinol hexamethylene urethane) (ESHU), an amphiphilic block copolymer that, in solution, undergoes a sol-gel transition upon heating from room temperature to body temperature. We performed in vitro release studies by injecting 10, 15 or 20% (w/v) ESHU containing 0.625, 1.25, 2.5 or 5 mg of bevacizumab into a 1% solution of hyaluronic acid at 37°C. At 1, 3, and 7 days and weekly thereafter, samples were obtained from the supernatant, and an enzyme-linked immunosorbent assay (ELISA) was used to determine the concentration of bevacizumab released. We evaluated the bioactivity of the released drug by quantifying the inhibition of tube formation using human umbilical vein endothelial cells (HUVECs) cultured on Matrigel.
The release profile of bevacizumab from ESHU is both dose- and concentration-dependent. In all experimental groups ESHU is capable of sustaining drug release in a near-linear fashion for approximately 12 weeks. The burst release from the gel at day 1 is less than 10% of the total drug loaded. Low gel concentration and/or high drug loading results in a larger burst and ultimately a more rapid release profile. The bevacizumab that is released from the gel is capable of inhibiting HUVEC tube formation when samples are mixed with culture media, suggesting that the released bevacizumab is bioactive, and that ESHU does not interfere with its mechanism of action.
By altering drug dose and gel concentration parameters the release profile of ESHU can be controlled. Compared to a clinical setting, in which bevacizumab must be injected monthly due to its short half-life, ESHU is capable of sustaining release over approximately 3 months in vitro, suggesting that it may ultimately be used to reduce injection frequency, improve patient compliance and enhance therapeutic efficacy.
This PDF is available to Subscribers Only