title: Synthesis and characterization of a pH responsive folic acid functionalized polymeric drug delivery system.
abstract: We report the computational analysis, synthesis and characterization of folate functionalized poly(styrene-alt-maleic anhydride), PSMA for drug delivery purpose. The selection of the proper linker between the polymer and the folic acid group was performed before conducting the synthesis using Density Functional Theory (DFT). The computational results showed the bio-degradable linker 2, 4-diaminobutyric acid, DABA as a good candidate allowing flexibility of the folic acid group while maintaining the pH sensitivity of PSMA, used as a trigger for drug release. The synthesis was subsequently carried out in multi-step experimental procedures. The functionalized polymer was characterized using InfraRed spectroscopy, Nuclear Magnetic Resonance and Dynamic Light Scattering confirming both the chemical structure and the pH responsiveness of PSMA-DABA-Folate polymers. This study provides an excellent example of how computational chemistry can be used in selection process for the functional materials and product characterization. The pH sensitive polymers are expected to be used in delivering anti-cancer drugs to solid tumors with overly expressed folic acid receptors.
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON, Canada.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON, Canada.
authors.forename: Matt
authors.initials: M
authors.lastname: McTaggart
authors.affiliation: Department of Chemistry and Chemical Engineering, Royal Military College of Canada, Kingston, ON, Canada. Electronic address: Cecile.malardier-jugroot@rmc.ca.
authors.forename: Cecile
authors.initials: C
authors.lastname: Malardier-Jugroot
mesh_terms: D000613:Aminobutyrates / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage; D003432:Cross-Linking Reagents / Q000737:chemistry; D003959:Diamines / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008298:Maleates / Q000737:chemistry*; D008958:Models, Molecular; D011137:Polystyrenes / Q000737:chemistry*
chemical_list: D000613:Aminobutyrates; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D003959:Diamines; D058973:Folate Receptors, GPI-Anchored; D008298:Maleates; D011137:Polystyrenes; C520889:poly(styrene-alt-maleic anhydride); C005959:2,4-diaminobutyric acid; D005492:Folic Acid
keywords: Amphiphilic copolymers; Drug delivery; Molecular modelling; pH-responsive