Modulation of efflux proteins by electromagnetic field for delivering azidothymidine and saquinavir into the brain.

Colloids and surfaces. B, Biointerfaces · 2012 · Mixed · Very low evidence

← Research stream

MixedVery low evidencePaper 4426

Study snapshot

PublicationColloids and surfaces. B, Biointerfaces · 2012

Study typein_vitro

Reported directionMixed

Evidence ratingVery low

Abstract

An exposure to an electromagnetic field (EMF) has been shown to enhance the membrane permeability of endothelial cells. This study investigates the effect of EMF on the modulation of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) for delivering saquinavir (SQV) and azidothymidine (AZT). To assess the transport of SQV and AZT, an EMF and P-gp/MRP (transport protein) inhibitors were employed to stimulate confluent human brain-microvascular endothelial cells (HBMECs) with the regulation of human astrocytes. SQV at 40 μM and AZT at 300 μM were acceptable dosages for the viability of HBMECs. Under an EMF, verapamil showed a higher ability to elevate the permeation across the blood-brain barrier (BBB) than probenecid during treating with SQV. The reverse was true during treating with AZT. After an exposure to an EMF and administration of SQV and AZT, P-gp and MRP1 localized on the luminal side of HBMECs, exhibiting polar characteristics of the cell membranes. The synergetic effect of an EMF exposure and efflux protein inhibition can be promising in delivering antiretroviral drugs across the BBB.

Machine Enhanced Logic

AI evidence extraction

Structured fields below were generated from the paper’s abstract and metadata to make the evidence easier to inspect. Automated extraction may be incomplete or incorrect; verify important details against the original paper.

Study typein_vitro

Effect directionmixed

PopulationNot supplied

Sample sizeNot supplied

ExposureNot supplied

Evidence strengthVery lowConfidence: 72% · Peer reviewed: yes

Main findings

In a human brain-microvascular endothelial cell model regulated by astrocytes, EMF exposure combined with efflux transporter inhibitors altered drug permeation: under EMF, verapamil increased SQV permeation more than probenecid, while for AZT the opposite pattern was observed. After EMF exposure with SQV/AZT administration, P-gp and MRP1 were localized on the luminal side of HBMECs, consistent with polarized membrane characteristics. The authors conclude that EMF exposure plus efflux protein inhibition may help deliver antiretroviral drugs across the BBB in this in vitro system.

Outcomes measured

Permeation/transport of saquinavir (SQV) and azidothymidine (AZT) across an in vitro blood-brain barrier model
Modulation/localization of efflux proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP/MRP1) in human brain-microvascular endothelial cells (HBMECs)
Cell viability of HBMECs at SQV 40 μM and AZT 300 μM

Limitations

No EMF parameters (frequency, intensity, SAR, duration) are provided in the abstract.
In vitro BBB/endothelial cell model; findings may not translate to in vivo brain delivery.
No sample size/replication details are provided in the abstract.

View raw extracted JSON

{
  "study_type": "in_vitro",
  "exposure": {
    "band": null,
    "source": null,
    "frequency_mhz": null,
    "sar_wkg": null,
    "duration": null
  },
  "population": null,
  "sample_size": null,
  "outcomes": [
    "Permeation/transport of saquinavir (SQV) and azidothymidine (AZT) across an in vitro blood-brain barrier model",
    "Modulation/localization of efflux proteins P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP/MRP1) in human brain-microvascular endothelial cells (HBMECs)",
    "Cell viability of HBMECs at SQV 40 μM and AZT 300 μM"
  ],
  "main_findings": "In a human brain-microvascular endothelial cell model regulated by astrocytes, EMF exposure combined with efflux transporter inhibitors altered drug permeation: under EMF, verapamil increased SQV permeation more than probenecid, while for AZT the opposite pattern was observed. After EMF exposure with SQV/AZT administration, P-gp and MRP1 were localized on the luminal side of HBMECs, consistent with polarized membrane characteristics. The authors conclude that EMF exposure plus efflux protein inhibition may help deliver antiretroviral drugs across the BBB in this in vitro system.",
  "effect_direction": "mixed",
  "limitations": [
    "No EMF parameters (frequency, intensity, SAR, duration) are provided in the abstract.",
    "In vitro BBB/endothelial cell model; findings may not translate to in vivo brain delivery.",
    "No sample size/replication details are provided in the abstract."
  ],
  "evidence_strength": "very_low",
  "confidence": 0.72,
  "peer_reviewed_likely": "yes",
  "keywords": [
    "electromagnetic field",
    "blood-brain barrier",
    "HBMEC",
    "astrocytes",
    "P-glycoprotein",
    "P-gp",
    "MRP",
    "MRP1",
    "efflux transporters",
    "saquinavir",
    "azidothymidine",
    "verapamil",
    "probenecid",
    "membrane permeability",
    "antiretroviral drug delivery"
  ],
  "suggested_hubs": [
    {
      "slug": "who-icnirp",
      "weight": 0.1,
      "reason": "General EMF exposure study, but no specific policy or guideline focus is stated."
    }
  ]
}

AI can be wrong. Always verify against the paper.

AI-extracted fields are generated from the abstract and metadata and may be incomplete or incorrect. This material is for informational purposes and is not medical advice.

Identifiers and source

DOI: 10.1016/j.colsurfb.2011.11.020
PubMed: 22136805

Read the original paper →

Related papers

← Back to the Research Library