Polyester dendritic systems for drug delivery applications: design, synthesis, and characterization.
Attachment of drugs to high molecular weight polymers can significantly improve both tumor targeting and therapeutic efficacy due to the enhanced permeability and retention effect observed in tumor tissue. However, the commercial availability of well-defined water-soluble polymeric systems with narrow polydispersities that are biocompatible, nontoxic, and nonimmunogenic is rather limited. To address this need, we have investigated dendritic polymers as promising scaffolds for the preparation of new soluble polymeric drug carriers due to their well-defined molecular architecture and their multiplicity of surface sites. Herein we show the design and synthesis of dendritic polyester systems based on the monomer unit 2,2-bis(hydroxymethyl)propanoic acid as a possible versatile drug carrier. The potent anticancer drug doxorubicin was attached via a pH-sensitive linkage to one of the carriers presented, demonstrating the feasibility of using these polyester dendritic structures to prepare a viable polymer-drug conjugate.
Ihre
Henrik R
HR
Department of Chemistry, University of California, Berkeley 94720-1460, USA.
Padilla De Jesús
Omayra L
OL
Szoka
Francis C
FC
Fréchet
Jean M J
JM
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D006880:Hydroxy Acids; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D011422:Propionates / Q000138:chemical synthesis*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D006880:Hydroxy Acids; D011091:Polyesters; D011422:Propionates; C110034:2,2-bis(hydroxymethyl)-propionic acid; D004317:Doxorubicin