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Fluorescence Anisotropy, FT-IR Spectroscopy and 31-P NMR Studies on the Interaction of Paclitaxel with Lipid Bilayers

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Lipids

Abstract

To understand the bilayer interaction with paclitaxel, fluorescence polarization, Fourier transform infrared spectroscopy (FT-IR) and 31-phosphorus nuclear magnetic resonance (31P-NMR) studies were performed on paclitaxel bearing liposomes. Fluorescence anisotropy of three probes namely, 1,6-diphenyl-1,3,5-hexatriene (DPH), 12-(9-anthroyloxy) stearic acid (12AS) and 8-anilino-1-naphthalene sulfonate (ANS) were monitored as a function of paclitaxel concentration in the unsaturated bilayers. The incorporation of paclitaxel decreased anisotropy of 12AS and ANS probes, while slightly increased anisotropy of DPH. Paclitaxel has a fluidizing effect in the upper region of the bilayer whereas the hydrophobic core is slightly rigidized. FT-IR spectroscopy showed an increase in the asymmetric and symmetric methylene stretching frequencies, splitting of methylene scissoring band and broadening of carbonyl stretching mode. These studies collectively ascertained that paclitaxel mainly occupies the cooperativity region and interact with the interfacial region of unsaturated bilayers and induces fluidity in the headgroup region of bilayer. At higher loadings (>3 mol%), paclitaxel might gradually tend to accumulate at the interface and eventually partition out of bilayer as a result of solute exclusion phenomenon, resulting in crystallization; seed non-bilayer phases, as revealed by 31P-NMR, thereby destabilizing liposomal formulations. In general, any membrane component which has a rigidization effect will decrease, while that with a fluidizing effect will increase, with a bearing on headgroup interactions, partitioning of paclitaxel into bilayers and stability of the liposomes.

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Abbreviations

12AS:

12-(9-Anthroyloxy) stearic acid

ANS:

8-Anilino-1-naphthalene sulfonate

DPH:

1,6-Diphenyl-1,3,5-hexatriene

FT-IR:

Fourier transform infrared spectroscopy

31P-NMR:

31-Phosphorus nuclear magnetic resonance

PC:

Phosphatidylcholine

PG:

Phosphatidylglycerol

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Authors and Affiliations

  1. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S Nagar, 160062, India

    Anand Babu Dhanikula & Ramesh Panchagnula

  2. Pharmaceutical R&D, VMPS, Pfizer Pharmaceutical India Pvt. Ltd., Thane Belapur Road, Turbhe, K.U. Bazar Post, Navi Mumbai, 400 705, India

    Ramesh Panchagnula

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  1. Anand Babu Dhanikula
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  2. Ramesh Panchagnula
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Correspondence to Ramesh Panchagnula.

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Dhanikula, A.B., Panchagnula, R. Fluorescence Anisotropy, FT-IR Spectroscopy and 31-P NMR Studies on the Interaction of Paclitaxel with Lipid Bilayers. Lipids 43, 569–579 (2008). https://doi.org/10.1007/s11745-008-3178-1

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  • DOI: https://doi.org/10.1007/s11745-008-3178-1

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