title: In situ and in silico evaluation of amine- and folate-terminated dendrimers as nanocarriers of anesthetics.
abstract: The search for new nano-systems for targeted biomedical applications and controlled drug release has attracted significant attention in polymer chemistry, pharmaceutics, and biomaterial science. Controlled drug delivery has many advantages over conventional drug administration, such as reduction of side effects, maintaining a stable plasma level concentration and improving the quality of life of patients. In this study, PAMAM G5 dendrimers and PAMAM G5-folic acid conjugates (PAMAM G5-FA) are synthesized and characterized by mass spectrometry (MALDI-MS). Controlled release studies at different pH values show that PAMAM G5-FA is a good candidate as a carrier for tramadol and morphine, while mathematical modeling is conducted, suggesting that the release process is governed by a diffusion mechanism. In addition, using molecular dynamics simulations, we investigate the structural and energetic properties that facilitate the encapsulation of tramadol and morphine by unmodified and functionalized PAMAM-G5 dendrimers at low, neutral and high pH. Our results correlate well with experimental data, confirming that tramadol and morphine may be encapsulated both by functionalized PAMAM dendrimers and unmodified PAMAM. Moreover, the simulations further reveal that hydrogen-bond and electrostatic interactions govern the affinity the dendrimers for both drugs. This information is envisioned to prove useful for the encapsulation of other drugs and for the design of novel functionalized dendrimers.
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Verónica
authors.initials: V
authors.lastname: Carrasco-Sánchez
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Ariela
authors.initials: A
authors.lastname: Vergara-Jaque
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Matías
authors.initials: M
authors.lastname: Zuñiga
authors.affiliation: Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, República 239, Santiago, Chile.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Comer
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Amalraj
authors.initials: A
authors.lastname: John
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Fabiane M
authors.initials: FM
authors.lastname: Nachtigall
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Oscar
authors.initials: O
authors.lastname: Valdes
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile.
authors.forename: Esteban F
authors.initials: EF
authors.lastname: Duran-Lara
authors.affiliation: Center for Bioinformatics and Integrative Biology, Universidad Andres Bello, República 239, Santiago, Chile. Electronic address: claudia.sandoval@unab.cl.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sandoval
authors.affiliation: Laboratory of Asymmetric Synthesis, Chemistry Institute of Natural Resources, Nanobiotechnology Division at University of Talca, Fraunhofer Chile Research Foundation - Center for Systems Biotechnology, FCR-CSB, Talca University, Talca, P.O. Box 747, Chile. Electronic address: lssantos@utalca.cl.
authors.forename: Leonardo S
authors.initials: LS
authors.lastname: Santos
mesh_terms: D000588:Amines / Q000737:chemistry*; D000777:Anesthetics / Q000008:administration & dosage*; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D004339:Drug Compounding; D005492:Folic Acid / Q000737:chemistry*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009020:Morphine / Q000008:administration & dosage; D053758:Nanoparticles / Q000737:chemistry*; D012995:Solubility; D014147:Tramadol / Q000008:administration & dosage
chemical_list: D000588:Amines; D000777:Anesthetics; D050091:Dendrimers; D004337:Drug Carriers; D014147:Tramadol; D009020:Morphine; D005492:Folic Acid
keywords: Drug delivery; MALDI-MS; MM-GBSA; Molecular dynamics; PAMAM dendrimers