Designing Macromolecules for Therapeutic Applications:  Polyester DendrimerPoly(ethylene oxide) “Bow-Tie” Hybrids with Tunable Molecular Weight and Architecture

• Published in: Journal of the American Chemical Society Vol. 124; no. 47; pp. 14137 - 14146
• Main Authors: Gillies, Elizabeth R, Fréchet, Jean M. J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.11.2002; Amer Chemical Soc
• Subjects: Applied sciences; Biological and medical sciences; Chemistry; Chemistry, Multidisciplinary; Drug Delivery Systems; Drug Design; Exact sciences and technology; General pharmacology; Medical sciences; Molecular Conformation; Molecular Weight; Organic polymers; Pharmacology. Drug treatments; Physical Sciences; Physicochemical properties. Structure-activity relationships; Physicochemistry of polymers; Polyesters - chemical synthesis; Polyesters - chemistry; Polyethylene Glycols - chemical synthesis; Polyethylene Glycols - chemistry; Polymers with particular structures; Preparation, kinetics, thermodynamics, mechanism and catalysts; Science & Technology; POLYMERS; TUMOR ACCUMULATION; IN-VITRO; MECHANISM; CONVERGENT APPROACH; DRUGS; DENDRIMERS; Ethylene oxide polymer; Time of flight mass spectroscopy; Molecular weight distribution; Functionalization; Pharmacological activity; Structure activity relation; Molecular weight determination; Supramolecular structure; Ester polymer; Property structure relationship; Dendritic structure
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja028100n

The design and preparation of new polyester dendrimer, poly(ethylene oxide) hybrid systems for drug delivery and related therapeutic applications, are described. These systems consist of two covalently attached polyester dendrons, where one dendron provides multiple functional handles for the attachment of therapeutically active moieties, while the other is used for attachment of solubilizing poly(ethylene oxide) chains. By varying the generation of the dendrons and the mass of the poly(ethylene oxide) chains, the molecular weight, architecture, and drug loading can be readily controlled. The “bow-tie” shaped dendritic scaffold was synthesized using both convergent and divergent methods, with orthogonal protecting groups on the periphery of the two dendrons. Poly(ethylene oxide) was then attached to the periphery of one dendron using an efficient coupling procedure. A small library of eight carriers with molecular weights ranging from about 20 kDa to 160 kDa were prepared and characterized by various techniques, confirming their well-defined structures.