title: Automated discovery of novel drug formulations using predictive iterated high throughput experimentation.
abstract: BACKGROUND
  We consider the problem of optimizing a liposomal drug formulation: a complex chemical system with many components (e.g., elements of a lipid library) that interact nonlinearly and synergistically in ways that cannot be predicted from first principles.
  
  
  RESULTS
  The optimization criterion in our experiments was the percent encapsulation of a target drug, Amphotericin B, detected experimentally via spectrophotometric assay. Optimization of such a complex system requires strategies that efficiently discover solutions in extremely large volumes of potential experimental space. We have designed and implemented a new strategy of evolutionary design of experiments (Evo-DoE), that efficiently explores high-dimensional spaces by coupling the power of computer and statistical modeling with experimentally measured responses in an iterative loop.
  
  
  CONCLUSIONS
  We demonstrate how iterative looping of modeling and experimentation can quickly produce new discoveries with significantly better experimental response, and how such looping can discover the chemical landscape underlying complex chemical systems.
authors.affiliation: ProtoLife Inc., San Francisco, California, United States of America.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caschera
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gazzola
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bedau
authors.forename: Carolina
authors.initials: C
authors.lastname: Bosch Moreno
authors.forename: Andrew
authors.initials: A
authors.lastname: Buchanan
authors.forename: James
authors.initials: J
authors.lastname: Cawse
authors.forename: Norman
authors.initials: N
authors.lastname: Packard
authors.forename: Martin M
authors.initials: MM
authors.lastname: Hanczyc
mesh_terms: D000666:Amphotericin B / Q000737:chemistry*; D001331:Automation; D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery
chemical_list: D000666:Amphotericin B