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Regulation of Lipid Membrane Partitioning of Tamoxifen by Ionic Strength and Cholesterol

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Abstract

Purpose

The purpose of this study was to inspect the interactions between an anti-breast cancer, TAM, with model of lipid membranes composed of either zwitterionic DPPC LUVs or anionic DPPG LUVs and how they depend on ionic strength and cholesterol.

Methods

The Kp of TAM into DPPC and DPPG LUVs were determined at three different NaCl concentrations by second derivative UV-Vis spectrophotometry. The effect of cholesterol incorporated into these LUVs on TAM’s Kp was also assessed. The ATR-FTIR measurements were carried out to verify structural changes within the acyl chain and head group regions of the liposomes upon TAM partitioning.

Results

Increasing salt concentration produced negligible impact on the partitioning of TAM into DPPC bilayer as its Kp remained unaffected whilst induced outstanding reduction of TAM’s Kp into DPPG liposomes. Furthermore, TAM was found to disorder the lipids’ acyl chains, which could result in an increase in the membrane fluidity, a necessary piece of information to refer to when prescribing TAM dosage for administration. Additionally, cholesterol showed astoundingly opposite contribution to the partitioning of TAM into the LUVs, as its Kp value reduced in DPPC/Chol bilayer yet increased in DPPG/Chol liposomes.

Conclusion

Ionic strength and cholesterol play a noteworthy role in regulation of TAM partitioning into lipid membranes as they could obstruct or promote such action.

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Abbreviations

ATR-FTIR :

Attenuated total reflection Fourier transformed infrared spectroscopy

CH 2 :

Acyl chain region of phospholipids

C═O :

Carbonyl region of phospholipids

DMPC :

dimyristoyl-L-α-phosphatidylcholine

DMPG :

dimyristoyl-L-α-phosphatidylglycerol

DPPC :

1,2-dipalmitoyl-sn-glycero-3-phosphocholine

DPPG :

1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol)

DSC :

Differential scanning calorimetry

DSPC :

1,2-distearoyl-sn-glycero-3-phosphocholine

ER :

Estrogen receptor

FTIR :

Fourier transformed infrared spectroscopy

Hepes :

4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid

K p :

Partition coefficient

LUVs :

Large unilamellar vesicles

NaCl :

Sodium chloride

PO 2 :

Phosphate region of phospholipids

TAM :

Tamoxifen

T m :

Transition temperature

UV-Vis :

Ultraviolet-visible spectrophotometry

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ACKNOWLEDGMENTS AND DISCLOSURES

This research was funded by the Vietnam National University in Ho Chi Minh City under grant number C2017-28-02.

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Correspondence to Trang T. Nguyen.

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Dao, U.P.N., Nguyen, Q.D. & Nguyen, T.T. Regulation of Lipid Membrane Partitioning of Tamoxifen by Ionic Strength and Cholesterol. Pharm Res 37, 53 (2020). https://doi.org/10.1007/s11095-020-2771-8

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Key Words

  • cholesterol
  • DPPC
  • DPPG
  • ionic strength
  • tamoxifen