Document Detail

Fenretinide-polyvinylalcohol conjugates: new systems allowing fenretinide intravenous administration.
MedLine Citation:
PMID:  17883277     Owner:  NLM     Status:  MEDLINE    
N-(4-hydroxyphenyl)retinamide (fenretinide, 4-HPR) has been shown to be active toward many tumors without appreciable side effects. However its in vitro activity does not match a correspondent efficacy in vivo. The main reason is that the drug's hydrophobicity hinders its bioavailability in the body fluids. Even if the drug is previously dissolved in organic solvents, such as ethanol or DMSO, the subsequent dilution in body fluids trigger its precipitation in fine aggregates characterized by very low dissolution efficiency, never reaching amounts suitable for therapeutic response. To date no intravenous formulation of 4-HPR exists on the market. The 4-HPR linkage to a hydrophilic polymer by a covalent bond easily hydrolyzable in aqueous environment is expected to increase the drug's aqueous solubility, providing the free drug after hydrolysis of the covalent bond. This may be a useful tool for the preparation of aqueous intravenous formulations of 4-HPR. For this purpose, we linked 4-HPR to polyvinylalcohol (PVA) by a carbonate bond at different drug/hydroxy vinyl monomer molar ratios. We demonstrated that conjugation increased 4-HPR aqueous solubility and strongly inhibited neuroblastoma cell proliferation. In addition, in an in vivo neuroblastoma metastatic model, we obtained a significant antitumor effect as a consequence of the improved drug bioavailability.
I Orienti; G Zuccari; V Bergamante; R Carosio; R Gotti; M Cilli; P G Montaldo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-21
Journal Detail:
Title:  Biomacromolecules     Volume:  8     ISSN:  1525-7797     ISO Abbreviation:  Biomacromolecules     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-10-08     Completed Date:  2007-12-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3258-62     Citation Subset:  IM    
Department of Pharmaceutical Sciences, University of Bologna, Bologna, Italy.
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MeSH Terms
Antineoplastic Agents / administration & dosage*
Biological Availability
Cell Line, Tumor
Cell Proliferation
Dimethyl Sulfoxide / chemistry
Drug Delivery Systems*
Fenretinide / administration & dosage*,  chemistry*
Infusions, Intravenous
Mice, Nude
Models, Chemical
Neoplasm Metastasis
Neuroblastoma / metabolism
Polyvinyl Alcohol / chemistry*
Reg. No./Substance:
0/Antineoplastic Agents; 65646-68-6/Fenretinide; 67-68-5/Dimethyl Sulfoxide; 9002-89-5/Polyvinyl Alcohol

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