Computer-aided design of bioerodible devices with optimal release characteristics: a cellular automata approach.

The development of a computational tool to design bioerodible devices with optimal release characteristics is presented. This computational tool uses cellular automata and parallel iterations to model and simulate the release of bioactive agents (drugs) from bioerodible matrices. The simulations can accurately model surface erosion processes in multicomponent systems of arbitrary geometry and with different dissolution rates for each component. Simulation results are analysed to show how the overall release rates are affected by the intrinsic dissolution rates, drug loading, porosity and the dispersion of the drug in the bioerodible matrix. A strongly non-linear dependence of release rates on drug loading and the intrinsic dissolution rates of the solid components is obtained and the effects of phase dispersion on the variability of release rates are elucidated. Finally, guidelines are presented for screening of alternatives to minimize the development effort and experimentation required for designing devices with desired release characteristics.

[1]  N A Peppas,et al.  New challenges in biomaterials. , 1994, Science.

[2]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[3]  D E Ingber,et al.  Preparation of poly(glycolic acid) bonded fiber structures for cell attachment and transplantation. , 1993, Journal of biomedical materials research.

[4]  G. Boering,et al.  Resorbable materials of poly(L-lactide). VII. In vivo and in vitro degradation. , 1987, Biomaterials.

[5]  Tommaso Toffoli,et al.  Cellular automata machines - a new environment for modeling , 1987, MIT Press series in scientific computation.

[6]  E. F. Codd,et al.  Cellular automata , 1968 .

[7]  Kyriacos Zygourakis,et al.  Development and temporal evolution of erosion fronts in bioerodible controlled release devices , 1990 .

[8]  Dean C. Hsieh.  Controlled release systems : fabrication technology , 1988 .

[9]  R. Bettini.  Biomaterials for drug and cell delivery: A.G. Mikos, R.M. Murphy, H. Bernstein and N.A. Peppas (Eds.), Material Research Society, Pittsburgh, 1994, 290 pp., $ 78 , 1995 .

[10]  G. Boering,et al.  Resorbable materials of poly(L-lactide). VI. Plates and screws for internal fracture fixation. , 1987, Biomaterials.

[11]  J J Hopfield,et al.  Neural networks and physical systems with emergent collective computational abilities. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Kyriacos Zygourakis.  Design of Bioerodible Devices with Optimal Release Characteristics , 1994 .

[13]  Francois Robert.  An introduction to discrete iterations , 1987 .

[14]  A. Friedman,et al.  Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas. , 1991, Journal of neurosurgery.

[15]  J. Kohn,et al.  Synthesis of poly(iminocarbonates): degradable polymers with potential applications as disposable plastics and as biomaterials , 1989 .

[16]  Kyriacos Zygourakis,et al.  Parallel iterations and cellular automata models for simulating pore structural transformations , 1991, CSC '91.

[17]  JEFFREY A. Hubbel,et al.  Surface‐grafted Cell‐binding Peptides in Tissue Engineering of the Vascular Graft a , 1992, Annals of the New York Academy of Sciences.

[18]  David O. Cooney,et al.  Effect of geometry on the dissolution of pharmaceutical tablets and other solids: Surface detachment kinetics controlling , 1972 .

[19]  J. Hubbell,et al.  Human endothelial cell interactions with surface-coupled adhesion peptides on a nonadhesive glass substrate and two polymeric biomaterials. , 1991, Journal of biomedical materials research.

[20]  Yves Robert,et al.  Automata networks in computer science : theory and applications , 1987 .

[21]  Robert Langer,et al.  Modeling of Polymer Erosion , 1993 .