title: Targeted conjugation of breast anticancer drug tamoxifen and its metabolites with synthetic polymers.
abstract: Conjugation of antitumor drug tamoxifen and its metabolites, 4-hydroxytamxifen and ednoxifen with synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3) and polyamidoamine (PAMAM-G4) dendrimers was studied in aqueous solution at pH 7.4. Multiple spectroscopic methods, transmission electron microscopy (TEM) and molecular modeling were used to characterize the drug binding process to synthetic polymers. Structural analysis showed that drug-polymer binding occurs via both H-bonding and hydrophobic contacts. The order of binding is PAMAM-G4>mPEG-PAMAM-G3>PEG-6000 with 4-hydroxttamoxifen forming more stable conjugate than tamoxifen and endoxifen. Transmission electron microscopy showed significant changes in carrier morphology with major changes in the shape of the polymer aggregate as drug encapsulation occurred. Modeling also showed that drug is located in the surface and in the internal cavities of PAMAM with the free binding energy of -3.79 for tamoxifen, -3.70 for 4-hydroxytamoxifen and -3.69kcal/mol for endoxifen, indicating of spontaneous drug-polymer interaction at room temperature.
authors.affiliation: Department of Chemistry-Biochemistry and Physics, University of Québec at Trois- Rivières, C. P. 500, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Sanyakamdhorn
authors.affiliation: Department of Chemistry-Biochemistry and Physics, University of Québec at Trois- Rivières, C. P. 500, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Agudelo
authors.affiliation: Department of Chemistry-Biochemistry and Physics, University of Québec at Trois- Rivières, C. P. 500, Trois-Rivières, Québec G9A 5H7, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Bekale
authors.affiliation: Department of Chemistry-Biochemistry and Physics, University of Québec at Trois- Rivières, C. P. 500, Trois-Rivières, Québec G9A 5H7, Canada. Electronic address: heidar-ali.tajmir-riahi@uqtr.ca.
authors.forename: H A
authors.initials: HA
authors.lastname: Tajmir-Riahi
mesh_terms: D050091:Dendrimers / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D046529:Microscopy, Electron, Transmission; D011073:Polyamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D011108:Polymers; D013629:Tamoxifen; C016601:afimoxifene; D011092:Polyethylene Glycols; C055492:4-hydroxy-N-desmethyltamoxifen; C028210:monomethoxypolyethylene glycol
keywords: Dendrimer; Encapsulation; Modeling; PEG; Spectroscopy; TEM; Tamoxifen