Development of drug delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected “programming” achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Whereas many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, the present research demonstrated that sequential release of four drugs can be maintained following implantation.

Cellulose acetate phthalate (CAP) and Pluronic F-127 combined together (70:30 wt:wt) create a rigid, surface eroding association polymer. To impart flexibility into the polymer system and allow for a drug delivery film that can contour to varying wound shapes, plasticizers were added. Triethyl citrate (TEC) or tributyl citrate (TBC) was combined with CAP and Pluronic F-127 at 0, 10, or 20 wt%. Mechanical analysis was performed on the films as they were prepared and following a 2 hour incubation in phosphate-buffered saline. Tensile tests showed that higher plasticizer content increased the % elongation but decreased the elastic modulus (E) and ultimate tensile strength (UTS). The effect TEC had on the % elongation was twice as much than that of TBC. After incubation, % elongation, E, and UTS all increased because plasticizer leached out of the films. MicroCT and SEM were performed on the samples both before and after incubation to determine how erosion and leaching of plasticizer affected the interior and exterior structure of the films. Porosity increased as plasticizer content increased, however, plasticizer content did not have a significant effect on the rate of erosion. The mechanical properties of CAP-Pluronic films can be adjusted by the type and amount of plasticizer added to the system and therefore can be tailored for different drug delivery applications.

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