title: Extended Release of Native Drug Conjugated in Polyketal Microparticles.
abstract: Polyketals, which can be biodegradable, have good biocompatibility, and are pH-sensitive, could have broad applicability in drug delivery and other biomedical applications. However, facile synthesis of high molecular weight polyketals is challenging, and short durations of drug release from polyketal particulate formulations limit their application in drug delivery. Here we report the synthesis of a di-isopropenyl ether monomer and its use to synthesize high molecular weight estradiol-polyketal conjugates by addition polymerization. Microparticles were prepared from the estradiol-polyketal conjugate, where estradiol was incorporated into the polymer backbone. The particles had high drug loading and significantly prolonged drug release. Release of estradiol from the drug-polyketal conjugate microparticles was acid-responsive, as evidenced by faster drug release at low pH and with co-incorporation of PLGA. Tissue reaction to the microparticles was benign in vivo. Polyketal drug conjugates are promising candidates for long-acting drug delivery systems to treat chronic diseases.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Shutao
authors.initials: S
authors.lastname: Guo
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Aoune
authors.initials: A
authors.lastname: Barhoumi
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Changyou
authors.initials: C
authors.lastname: Zhan
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Tong
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Claudia
authors.initials: C
authors.lastname: Santamaria
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School , 300 Longwood Avenue, Boston, Massachusetts 02115, United States.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D002384:Catalysis; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage / Q000737:chemistry; D004967:Estrogens / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004967:Estrogens; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004958:Estradiol