TY - JOUR

T1 - Mucus-PVPA (mucus Phospholipid Vesicle-based Permeation Assay)

T2 - An artificial permeability tool for drug screening and formulation development

AU - Falavigna, Margherita

AU - Klitgaard, Mette

AU - Brase, Christina

AU - Ternullo, Selenia

AU - Škalko-Basnet, Nataša

AU - Flaten, Gøril Eide

N1 - Copyright © 2017 Elsevier B.V. All rights reserved.

PY - 2018/2/15

Y1 - 2018/2/15

N2 - The mucus layer covering all mucosal surfaces in our body is the first barrier encountered by drugs before their potential absorption through epithelial tissues, and could thus affect the drugs' permeability and their effectiveness. Therefore, it is of key importance to have in vitro permeability models that can mimic this specific environment. For this purpose, the novel mucus phospholipid vesicle-based permeation assay (mucus-PVPA) has been developed and used for permeability screening of drugs and formulations. The model proved to be stable under the chosen conditions and demonstrated the ability to discriminate between compounds with different chemical structures and properties. Overall, a decrease in drug permeability was found in the presence of mucus on top of the PVPA barriers, as expected. Moreover, mucoadhesive (chitosan-coated) and mucopenetrating (PEGylated) liposomes were investigated in the newly developed model. The mucus-PVPA was able to distinguish between the different liposomal formulations, confirming the penetration potential of the tested formulations and the related drug permeability. The mucus-PVPA model appears to be a promising in vitro tool able to mimic the environment of mucosal tissues, and could therefore be used for further drug permeability screening and formulation development.

AB - The mucus layer covering all mucosal surfaces in our body is the first barrier encountered by drugs before their potential absorption through epithelial tissues, and could thus affect the drugs' permeability and their effectiveness. Therefore, it is of key importance to have in vitro permeability models that can mimic this specific environment. For this purpose, the novel mucus phospholipid vesicle-based permeation assay (mucus-PVPA) has been developed and used for permeability screening of drugs and formulations. The model proved to be stable under the chosen conditions and demonstrated the ability to discriminate between compounds with different chemical structures and properties. Overall, a decrease in drug permeability was found in the presence of mucus on top of the PVPA barriers, as expected. Moreover, mucoadhesive (chitosan-coated) and mucopenetrating (PEGylated) liposomes were investigated in the newly developed model. The mucus-PVPA was able to distinguish between the different liposomal formulations, confirming the penetration potential of the tested formulations and the related drug permeability. The mucus-PVPA model appears to be a promising in vitro tool able to mimic the environment of mucosal tissues, and could therefore be used for further drug permeability screening and formulation development.

KW - Animals

KW - Biological Assay/methods

KW - Chemistry, Pharmaceutical/methods

KW - Drug Evaluation, Preclinical/methods

KW - Humans

KW - Liposomes/chemistry

KW - Mucus/chemistry

KW - Permeability

KW - Phospholipids/chemistry

U2 - 10.1016/j.ijpharm.2017.12.038

DO - 10.1016/j.ijpharm.2017.12.038

M3 - Journal article

C2 - 29288094

VL - 537

SP - 213

EP - 222

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -