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LDL Induced Association of Anionic Liposomes with Cells and Delivery of Contents as Shown by the Increase in Potency of Liposome Dependent Drugs

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Abstract

Purpose. To establish whether anionic liposomes interact with the low-density lipoprotein (LDL) receptor, to determine the role of lipoproteins in this interaction, and whether the association causes functional delivery of encapsulated drugs.

Methods. The cell lines used were CV1-P and CHO wild type, both of which express the LDL receptor, and CHOldlA7, which lacks the LDL receptor. Cellular association of encapsulated methotrexate and fluorescein, labeled phosphatidylethanolamine in the lipid bilayer, was measured. Potency of three liposome dependent drugs (N-phosphonacetyl-L-aspartic acid, fluoroorotic acid, and methotrexate-γ-aspartate) was also measured by growth inhibition.

Results. Association of liposomes containing at least 75 mol egg phosphatidylglycerol (ePG)/100 mol phospholipid with cells grown in defined medium supplemented with 1.0 mg/ml LDL was up to 30-fold higher with CV1-P or CHO wild type cells than with CHOldlA7, and 5-fold higher than association in defined medium lacking LDL. The addition of LDL did not yield any elevation of cellular association of distearoylphosphatidylglycerol liposomes. Increased association was paralleled by a corresponding increase in potency of all three liposome dependent drugs tested.

Conclusions. ePG liposomes interact with the LDL receptor in an LDL-dependent fashion, and the interaction results in the delivery of contents to cells.

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Authors and Affiliations

  1. School of Pharmacy, University of Wisconsin-Madison, 425 N. Charter Street, Madison, Wisconsin, 53706

    Ketan Amin & Timothy D. Heath

  2. School of Pharmacy, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, C-238, Denver, Colorado, 80262

    Ka-Yun Ng

  3. Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706

    Carolyn S. Brown

  4. Mova Pharmaceuticals, PO Box 8639, Caguas, Puerto Rico, 00726

    Maria S. Bruno

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Amin, K., Ng, KY., Brown, C.S. et al. LDL Induced Association of Anionic Liposomes with Cells and Delivery of Contents as Shown by the Increase in Potency of Liposome Dependent Drugs. Pharm Res 18, 914–921 (2001). https://doi.org/10.1023/A:1010971808006

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