title: Mathematical Modeling and Experimental Validation of Nanoemulsion-Based Drug Transport across Cellular Barriers.
abstract: OBJECTIVE
  Nanoemulsions have shown potential in delivering drug across epithelial and endothelial cell barriers, which express efflux transporters. However, their transport mechanisms are not entirely understood. Our goal was to investigate the cellular permeability of nanoemulsion-encapsulated drugs and apply mathematical modeling to elucidate transport mechanisms and sensitive nanoemulsion attributes.
  
  
  METHODS
  Transport studies were performed in Caco-2 cells, using fish oil nanoemulsions and a model substrate, rhodamine-123. Permeability data was modeled using a semi-mechanistic approach, capturing the following cellular processes: endocytotic uptake of the nanoemulsion, release of rhodamine-123 from the nanoemulsion, efflux and passive permeability of rhodamine-123 in aqueous solution.
  
  
  RESULTS
  Nanoemulsions not only improved the permeability of rhodamine-123, but were also less sensitive to efflux transporters. The model captured bidirectional permeability results and identified sensitive processes, such as the release of the nanoemulsion-encapsulated drug and cellular uptake of the nanoemulsion.
  
  
  CONCLUSIONS
  Mathematical description of cellular processes, improved our understanding of transport mechanisms, such as nanoemulsions don't inhibit efflux to improve drug permeability. Instead, their endocytotic uptake, results in higher intracellular drug concentrations, thereby increasing the concentration gradient and transcellular permeability across biological barriers. Modeling results indicated optimizing nanoemulsion attributes like the droplet size and intracellular drug release rate, may further improve drug permeability.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA.
authors.forename: Ekta
authors.initials: E
authors.lastname: Kadakia
authors.affiliation: Novartis Institute of Biomedical Research, Cambridge, Massachusetts, 02142, USA.
authors.forename: Lipa
authors.initials: L
authors.lastname: Shah
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, Boston, Massachusetts, 02115, USA. m.amiji@neu.edu.
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
mesh_terms: D001692:Biological Transport; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D065546:Drug Liberation; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D005395:Fish Oils; D006801:Humans; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism*; D012996:Solutions
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005395:Fish Oils; D012235:Rhodamines; D012996:Solutions
keywords: cellular transport mathematical model; oil-in-water nanoemulsion; rhodamine-123