title: Structural analysis of doxorubicin-polymer conjugates.
abstract: Synthetic polymers poly(ethylene glycol) (PEG), methoxypoly (ethylene glycol) polyamidoamine (mPEG-PAMAM-G3) and polyamidoamine (PAMAM-G4) dendrimers were used for encapsulation of antibiotic drug doxorubicin (Dox) and its analogue N-(trifluoroacetyl) doxorubicin (FDox) 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 Dox forming more stable conjugate than FDox. 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 -4.14 kcal/mol for Dox and -3.93 kcal/mol for FDox, 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: 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.
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. Electronic address: heidar-ali.tajmir-riahi@uqtr.ca.
authors.forename: H A
authors.initials: HA
authors.lastname: Tajmir-Riahi
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry*; D050091:Dendrimers; D004317:Doxorubicin / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009757:Nylons; D011092:Polyethylene Glycols; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D012996:Solutions
chemical_list: D000903:Antibiotics, Antineoplastic; D050091:Dendrimers; D009757:Nylons; C522260:PAMAM G3.5 dendrimer; C520550:PAMAM-G4; D011108:Polymers; D012996:Solutions; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Dendrimer; Drug delivery; Encapsulation; Modeling; PEG; Spectroscopy; TEM