Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

Naderkhani, Elenaz; Vasskog, Terje; Flaten, Gøril Eide

doi:10.1016/j.ejps.2015.03.017

Cited by 11 publications

(6 citation statements)

References 51 publications

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“…ATN, CAF, HYD, and NPR were quantified at 273, 272, 247, and 270 nm, respectively. Moreover, the electrical resistance across the PVPA barriers was measured to confirm their integrity and proper functionality, as previously described [20][21][22][23]. The P app (apparent permeability, cm/sec) of the investigated drugs was calculated by Equation (2).…”

Section: In Vitro Permeability Studymentioning

confidence: 99%

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

et al. 2020

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Mucosal drug delivery accounts for various administration routes (i.e., oral, vaginal, ocular, pulmonary, etc.) and offers a vast surface for the permeation of drugs. However, the mucus layer which shields and lubricates all mucosal tissues can compromise drugs from reaching the epithelial site, thus affecting their absorption and therapeutic effect. Therefore, the effect of the mucus layer on drug absorption has to be evaluated early in the drug-development phase, prior to in vivo studies. For this reason, we developed a simple, cost-effective and reproducible method employing UV-visible localized spectroscopy for the assessment of the interaction between mucin and drugs with different physicochemical characteristics. The mucin–drug interaction was investigated by measuring the drug relative diffusivity (Drel) in the presence of mucin, and the method was validated by fitting experimental and mathematical data. In vitro permeability studies were also performed using the mucus-covered artificial permeation barrier (mucus–PVPA, Phospholipid Vesicle-based Permeation Assay) for comparison. The obtained results showed that the diffusion of drugs was hampered by the presence of mucin, especially at higher concentrations. This novel method proved to be suitable for the investigation on the extent of mucin–drug interaction and can be successfully used to assess the impact that the mucus layer has on drug absorption.

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Section: In Vitro Permeability Studymentioning

confidence: 99%

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

et al. 2020

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“…As shown in Figure 4, the percentage of the drug recovered in the donor and acceptor compartment at the end of the permeation study never reached 100%, indicating that part of the drug could be found in the PVPA barriers. In this regard, it has been previously demonstrated that drug retention in the barriers can occur for more lipophilic compounds due to their affinity for the lipidic barrier, whereas hydrophilic drugs, which have higher affinity for the aqueous donor/acceptor medium, tend to be retained to a lower extent in the PVPA barriers [42]. Therefore, due to its high lipophilicity (LogP 3.97, [27]), ibuprofen can be retained in the barriers, leading to a low recovery when comparing the amount of the drug at the start of the permeation experiment with the one found in the donor and acceptor compartment after 5 h of permeation study.…”

Section: Recovery Of Ibuprofen In the Donor And Acceptor Compartmentmentioning

confidence: 99%

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

et al. 2020

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Drug administration to the vaginal site has gained increasing attention in past decades, highlighting the need for reliable in vitro methods to assess the performance of novel formulations. To optimize formulations destined for the vaginal site, it is important to evaluate the drug retention within the vagina as well as its permeation across the mucosa, particularly in the presence of vaginal fluids. Herewith, the vaginal-PVPA (Phospholipid Vesicle-based Permeation Assay) in vitro permeability model was validated as a tool to evaluate the permeation of the anti-inflammatory drug ibuprofen from liposomal formulations (i.e., plain and chitosan-coated liposomes). Drug permeation was assessed in the presence and absence of mucus and simulated vaginal fluid (SVF) at pH conditions mimicking both the healthy vaginal premenopausal conditions and vaginal infection/pre-puberty/post-menopause state. The permeation of ibuprofen proved to depend on the type of formulation (i.e., chitosan-coated liposomes exhibited lower drug permeation), the mucoadhesive formulation properties and pH condition. This study highlights both the importance of mucus and SVF in the vaginal model to better understand and predict the in vivo performance of formulations destined for vaginal administration, and the suitability of the vaginal-PVPA model for such investigations.

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“…As earlier described by our group (Flaten et al, 2006a, b), the concentrations of the drugs investigated in the study were chosen in order to reach a concentration in the acceptor compartment that was below the solubility limits and thus to obtain sink conditions. In order to determine any changes in the barriers' integrity caused by the addition of mucus on top of the PVPA barriers, the amount of phospholipids released after the addition of the mucus layer was measured by the modified phosphorus assay (Bartlett, 1959) as previously described by us (Naderkhani et al, 2015).…”

Section: In Vitro Permeability Study Using the Mucus-pvpamentioning

confidence: 99%

Mucus-PVPA (mucus Phospholipid Vesicle-based Permeation Assay): An artificial permeability tool for drug screening and formulation development

Falavigna

Klitgaard

Brase

et al. 2018

International Journal of Pharmaceutics

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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.

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Biomimetic PVPA in vitro model for estimation of the intestinal drug permeability using fasted and fed state simulated intestinal fluids

Cited by 11 publications

References 51 publications

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

Impact of Mucin on Drug Diffusion: Development of a Straightforward In Vitro Method for the Determination of Drug Diffusivity in the Presence of Mucin

The Vaginal-PVPA: A Vaginal Mucosa-Mimicking In Vitro Permeation Tool for Evaluation of Mucoadhesive Formulations

Mucus-PVPA (mucus Phospholipid Vesicle-based Permeation Assay): An artificial permeability tool for drug screening and formulation development

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