title: Comparison of sequential drug release in vitro and in vivo.
abstract: 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 that release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, whereas this research demonstrated that sequential release of four drugs can be maintained following implantation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1302-1310, 2016.
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky.
authors.forename: Sharath C
authors.initials: SC
authors.lastname: Sundararaj
authors.affiliation: Division of Periodontics, College of Dentistry, University of Kentucky, Lexington, Kentucky.
authors.forename: Mohanad
authors.initials: M
authors.lastname: Al-Sabbagh
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Rabek
authors.affiliation: Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dziubla
authors.affiliation: Division of Periodontics, College of Dentistry, University of Kentucky, Lexington, Kentucky.
authors.forename: Mark V
authors.initials: MV
authors.lastname: Thomas
authors.affiliation: Department of Biomedical Engineering, University of Kentucky, Lexington, Kentucky. puleo@uky.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Puleo
mesh_terms: D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004343:Drug Implants; D008297:Male; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004343:Drug Implants; D020442:Poloxamer; D002482:Cellulose; C011708:cellulose acetate phthalate
keywords: Pluronic F-127; cellulose acetate phthalate; in vitro drug release; in vivo drug release; sequential drug delivery