Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex.

Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Research Abstract Details 

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Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Abstract Text:

Barry J Maurer,Ondrej Kalous,David W Yesair,Xiaqin Wu,Jitka Janeba,Vanessa Maldonado,Vazgen Khankaldyyan,Tomas Frgala,Bee-Chun Sun,R Travis McKee,Stephen W Burgess,Walter A Shaw,C Patrick Reynolds,

PURPOSE: Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is a cytotoxic retinoid that suffers from a wide interpatient variation in bioavailability when delivered orally in a corn oil capsule. The poor bioavailability of the capsule formulation may have limited responses in clinical trials, and the large capsules are not suitable for young children. To support the hypothesis that a novel organized lipid matrix, LYM-X-SORB, can increase the oral bioavailability of fenretinide, fenretinide in LYM-X-SORB matrix and in a powderized LYM-X-SORB formulation was delivered to mice. EXPERIMENTAL DESIGN: Fenretinide was delivered orally to mice as the contents of the corn oil capsule, in LYM-X-SORB matrix (4-HPR/LYM-X-SORB matrix) or in a LYM-X-SORB matrix powderized with sugar and flour (4-HPR/LYM-X-SORB oral powder). Levels of 4-HPR, and its principal metabolite, N-(4-methoxyphenyl)retinamide, were assayed in plasma and tissues. RESULTS: In a dose-responsive manner, from 120 to 360 mg/kg/d, delivery to mice of 4-HPR in LYM-X-SORB matrix, or as 4-HPR/LYM-X-SORB oral powder, increased 4-HPR plasma levels up to 4-fold (P<0.01) and increased tissue levels up to 7-fold (P<0.01) compared with similar doses of 4-HPR delivered using capsule contents. Metabolite [N-(4-methoxyphenyl)retinamide] levels mirrored 4-HPR levels. Two human neuroblastoma murine xenograft models showed increased survival (P<0.03), when treated with 4-HPR/LYM-X-SORB oral powder, confirming the bioactivity of the formulation. CONCLUSIONS: 4-HPR/LYM-X-SORB oral powder is a novel, oral drug delivery formulation, suitable for pediatric use, which warrants further development for the delivery of fenretinide in the treatment of cancer. A phase I clinical trial in pediatric neuroblastoma is in progress.

Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Publishing Authors By Initials

BJ Maurer,O Kalous,DW Yesair,X Wu,J Janeba,V Maldonado,V Khankaldyyan,T Frgala,BC Sun,RT McKee,SW Burgess,WA Shaw,CP Reynolds,

For similar biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research abstracts see: biochemical phenomena, metabolism, and nutrition: metabolism: pharmacokinetics: tissue distribution research

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Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 3079-86

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: May

YEAR: 2007

Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502500

Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Keywords Mesh Terms:

KEYWORDS: Tissue Distribution

MESH TERMS: drug therapy

Chemical & Substance for Abstract: Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex. Information

Substance Name: Fenretinide

Registry Number: 65646-68-6

Grant and Affiliation Information for Improved oral delivery of N-(4-hydroxyphenyl)retinamide with a novel LYM-X-SORB organized lipid complex.

AFFILIATION: Developmental Therapeutics Program, USC-CHLA Institute for Pediatric Clinical Research and Division of Hematology-Oncology, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA. bmaurer@chla.usc.edu

Country: United States

AGENCY: United States NCI

GRANT: CA81403

ACRONYM: CA

MEDLINETA: Clin Cancer Res

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