Abstract:
:A wide range of length and time scales are relevant to pharmacology, especially in drug development, drug design and drug delivery. Therefore, multiscale computational modeling and simulation methods and paradigms that advance the linkage of phenomena occurring at these multiple scales have become increasingly important. Multiscale approaches present in silico opportunities to advance laboratory research to bedside clinical applications in pharmaceuticals research. This is achievable through the capability of modeling to reveal phenomena occurring across multiple spatial and temporal scales, which are not otherwise readily accessible to experimentation. The resultant models, when validated, are capable of making testable predictions to guide drug design and delivery. In this review we describe the goals, methods, and opportunities of multiscale modeling in drug design and development. We demonstrate the impact of multiple scales of modeling in this field. We indicate the common mathematical and computational techniques employed for multiscale modeling approaches used in pharmacometric and systems pharmacology models in drug development and present several examples illustrating the current state-of-the-art models for (1) excitable systems and applications in cardiac disease; (2) stem cell driven complex biosystems; (3) nanoparticle delivery, with applications to angiogenesis and cancer therapy; (4) host-pathogen interactions and their use in metabolic disorders, inflammation and sepsis; and (5) computer-aided design of nanomedical systems. We conclude with a focus on barriers to successful clinical translation of drug development, drug design and drug delivery multiscale models.
journal_name
Ann Biomed Engjournal_title
Annals of biomedical engineeringauthors
Clancy CE,An G,Cannon WR,Liu Y,May EE,Ortoleva P,Popel AS,Sluka JP,Su J,Vicini P,Zhou X,Eckmann DMdoi
10.1007/s10439-016-1563-0subject
Has Abstractpub_date
2016-09-01 00:00:00pages
2591-610issue
9eissn
0090-6964issn
1573-9686pii
10.1007/s10439-016-1563-0journal_volume
44pub_type
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