title: Biodegradable block copolymers for delivery of proteins and water-insoluble drugs.
abstract: Release of several drugs from new ABA-type biodegradable thermal gels, ReGel, including proteins and conventional molecules, are presented. These are biodegradable, biocompatible polymers that demonstrate reverse thermal gelation properties. Organic solvents are not used in the synthesis, purification, or formulation of these polymers. The unique characteristics of ReGel hinge on the following two key properties: (1) ReGel is a water soluble, biodegradable polymer at temperatures below the gel transition temperature; (2) ReGel forms a water-insoluble gel once injected. This is consistent with a hydrophobically bonded gel state where all interactions are physical, with no covalent crosslinking. An increase in viscosity of approximately 4 orders of magnitude accompanies the sol--gel transition. The gel forms a controlled release drug depot with delivery times ranging from 1 to 6 weeks. ReGel's inherent ability to solubilize (400 to >2000-fold) and stabilize poorly soluble and sensitive drugs, including proteins is a substantial benefit. The gel provided excellent control of the release of paclitaxel for approximately 50 days. Direct intratumoral injection of ReGel/paclitaxel (OncoGel) results in a slow clearance of paclitaxel from the injection site with minimal distribution into any organ. Efficacies equivalent to maximum tolerated systemic dosing were observed at OncoGel doses that were 10-fold lower. Data on protein release (pGH, G-CSF, insulin, rHbsAg) and polymer biocompatibility are discussed.
authors.affiliation: MacroMed Inc., 9520 South State Street, Sandy, UT 84070, USA. macromed@macromed.com
authors.forename: G M
authors.initials: GM
authors.lastname: Zentner
authors.forename: R
authors.initials: R
authors.lastname: Rathi
authors.forename: C
authors.initials: C
authors.lastname: Shih
authors.forename: J C
authors.initials: JC
authors.lastname: McRea
authors.forename: M H
authors.initials: MH
authors.lastname: Seo
authors.forename: H
authors.initials: H
authors.lastname: Oh
authors.forename: B G
authors.initials: BG
authors.lastname: Rhee
authors.forename: J
authors.initials: J
authors.lastname: Mestecky
authors.forename: Z
authors.initials: Z
authors.lastname: Moldoveanu
authors.forename: M
authors.initials: M
authors.lastname: Morgan
authors.forename: S
authors.initials: S
authors.lastname: Weitman
mesh_terms: D016503:Drug Delivery Systems; D004548:Elasticity; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000737:chemistry*; D006510:Hepatitis B Antibodies / Q000032:analysis; D019344:Lactic Acid; D008422:Materials Testing; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage*; D012995:Solubility; D012997:Solvents; D014783:Viscosity
chemical_list: D005079:Excipients; D006510:Hepatitis B Antibodies; D011108:Polymers; D011506:Proteins; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols