Caco-2 Cell Conditions Enabling Studies of Drug Absorption from Digestible Lipid-Based Formulations

Pharmaceutical Research
Janneke Keemink, Christel A S Bergström

Abstract

To identify conditions allowing the use of cell-based models for studies of drug absorption during in vitro lipolysis of lipid-based formulations (LBFs). Caco-2 was selected as the cell-based model system. Monolayer integrity was evaluated by measuring mannitol permeability after incubating Caco-2 cells in the presence of components available during lipolysis. Pure excipients and formulations representing the lipid formulation classification system (LFCS) were evaluated before and after digestion. Porcine mucin was evaluated for its capacity to protect the cell monolayer. Most undigested formulations were compatible with the cells (II-LC, IIIB-LC, and IV) although some needed mucin to protect against damaging effects (II-MC, IIIB-MC, I-LC, and IIIA-LC). The pancreatic extract commonly used in digestion studies was incompatible with the cells but the Caco-2 monolayers could withstand immobilized recombinant lipase. Upon digestion, long chain formulations caused more damage to Caco-2 cells than their undigested counterparts whereas medium chain formulations showed better tolerability after digestion. Most LBFs and components thereof (undigested and digested) are compatible with Caco-2 cells. Pancreatic enzyme is not tolerated by ...Continue Reading

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Citations

May 22, 2020·Pharmaceutical Research·Oliver J Hedge, Christel A S Bergström
Jul 3, 2019·Advanced Drug Delivery Reviews·Ragna BerthelsenAnette Müllertz
Jan 16, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Estelle J A SuysChristopher J H Porter
Jan 26, 2021·Journal of Colloid and Interface Science·Zeynep Burcu Akkuş-DağdevirenAndreas Bernkop-Schnürch
Apr 29, 2020·Journal of Colloid and Interface Science·Claudia HemptStefan Salentinig
Feb 22, 2021·Advanced Drug Delivery Reviews·Zahari VinarovPatrick Augustijns
Jun 30, 2021·Biotechnology Advances·Areen AshkarMaya Davidovich-Pinhas
Jun 29, 2021·Frontiers in Cell and Developmental Biology·Anna C PhamBen J Boyd
Jan 11, 2019·Molecular Pharmaceutics·Janneke KeeminkChristel A S Bergström

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