Liposomal formulation of retinoids designed for enzyme triggered release

Palle J. Pedersen; Sidsel K. Adolph; Arun K. Subramanian; Ahmad Arouri; Thomas L. Andresen; Ole G. Mouritsen; Robert Madsen; Mogens W. Madsen; Günther H. Peters; Mads H. Clausen

doi:10.1021/jm100190c

Liposomal formulation of retinoids designed for enzyme triggered release

Palle J. Pedersen, Sidsel K. Adolph, Arun K. Subramanian, Ahmad Arouri, Thomas L. Andresen, Ole G. Mouritsen, Robert Madsen, Mogens W. Madsen, Günther H. Peters, Mads H. Clausen

64 Citations (Scopus)

Abstract

The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A₂ IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A₂, the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC₅₀ values in the range of 3-19 μM toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A ₂, while no significant cell death was observed in the absence of the enzyme.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	53
Issue number	9
Pages (from-to)	3782-3792
Number of pages	11
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm100190c
Publication status	Published - 13 May 2010

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10.1021/jm100190c

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@article{24edb96073234401923e0de1b65719ef,

title = "Liposomal formulation of retinoids designed for enzyme triggered release",

abstract = "The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A2 IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A2, the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 μM toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A 2, while no significant cell death was observed in the absence of the enzyme.",

author = "Pedersen, {Palle J.} and Adolph, {Sidsel K.} and Subramanian, {Arun K.} and Ahmad Arouri and Andresen, {Thomas L.} and Mouritsen, {Ole G.} and Robert Madsen and Madsen, {Mogens W.} and Peters, {G{\"u}nther H.} and Clausen, {Mads H.}",

year = "2010",

month = may,

day = "13",

doi = "10.1021/jm100190c",

language = "English",

volume = "53",

pages = "3782--3792",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

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TY - JOUR

T1 - Liposomal formulation of retinoids designed for enzyme triggered release

AU - Pedersen, Palle J.

AU - Adolph, Sidsel K.

AU - Subramanian, Arun K.

AU - Arouri, Ahmad

AU - Andresen, Thomas L.

AU - Mouritsen, Ole G.

AU - Madsen, Robert

AU - Madsen, Mogens W.

AU - Peters, Günther H.

AU - Clausen, Mads H.

PY - 2010/5/13

Y1 - 2010/5/13

N2 - The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A2 IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A2, the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 μM toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A 2, while no significant cell death was observed in the absence of the enzyme.

AB - The design of retinoid phospholipid prodrugs is described based on molecular dynamics simulations and cytotoxicity studies of synthetic retinoid esters. The prodrugs are degradable by secretory phospholipase A2 IIA and have potential in liposomal drug delivery targeting tumors. We have synthesized four different retinoid phospholipid prodrugs and shown that they form particles in the liposome size region with average diameters of 94-118 nm. Upon subjection to phospholipase A2, the lipid prodrugs were hydrolyzed, releasing cytotoxic retinoids and lysolipids. The formulated lipid prodrugs displayed IC50 values in the range of 3-19 μM toward HT-29 and Colo205 colon cancer cells in the presence of phospholipase A 2, while no significant cell death was observed in the absence of the enzyme.

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U2 - 10.1021/jm100190c

DO - 10.1021/jm100190c

M3 - Journal article

C2 - 20405849

AN - SCOPUS:77952020524

SN - 0022-2623

VL - 53

SP - 3782

EP - 3792

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 9

ER -

Liposomal formulation of retinoids designed for enzyme triggered release

Abstract

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