title: Drug release from a pH-sensitive multiblock co-polymer thermogel.
abstract: A Pluronic(®)-based pH-sensitive multiblock co-polymer thermogel has been proposed for sustained release of therapeutic agents. Hydrophobic small-molecule drugs (paclitaxel and camptothecin) and model hy-drophilic macromolecules (fluorescein-labeled dextrans of molecular mass 10, 20, 40, 150 and 250 kDa) were successfully loaded into and released from the thermogels. Drug-loaded polymer solutions were characterized for gelation behavior and micelle size. Drug loading increased the size of the multiblock co-polymer micelles from 20 to 100 nm. The co-polymer improved paclitaxel and camptothecin loading in an aqueous solution by 6900- and 1050-fold, respectively, compared to their solubility in water. The ther-mogels released loaded drugs in a pH-dependent fashion, regardless of their properties. At pH 5.0 and 6.5, paclitaxel and camptothecin completely released in 4 and 15 days, respectively, by a combined mechanism of diffusion and erosion. At neutral pH, diffusion predominated gel erosion to sustain the drug release up to 40 days. Fluorescein-labeled dextran release from the thermogels showed a similar pH-dependent trend as the hydrophobic small molecule drugs. However, dextran release at neutral pH was entirely dependent on the molecular mass of the dextran. Low-molecular-mass (10 and 20 kDa) dextrans were completely released in 12 and 21 days, respectively, while high-molecular-mass (⩾40 kDa) dextrans being continuously released over 36 days, indicating that the threshold of molecular weight necessary for sustained release of a hydrophilic macromolecule from this thermogel (e.g., enzymes, monoclonal antibodies and immunotoxins) is 40 kDa. Taken together, the MBCP thermogel showed potential as a controlled drug-delivery system that showed sustained release of both hydrophilic and lipophilic molecules.
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , The University of Mississippi , University , MS-38677 , USA.
authors.forename: Vivek Kumar
authors.initials: VK
authors.lastname: Garripelli
authors.forename: Ran
authors.initials: R
authors.lastname: Namgung
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Kim
authors.forename: Seongbong
authors.initials: S
authors.lastname: Jo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002166:Camptothecin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000737:chemistry; D003911:Dextrans / Q000008:administration & dosage / Q000493:pharmacokinetics; D004058:Diffusion; D065546:Drug Liberation; D005782:Gels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008823:Micelles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D012996:Solutions; D013696:Temperature; D014867:Water / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D003911:Dextrans; D005782:Gels; D008823:Micelles; D011108:Polymers; D012996:Solutions; D014867:Water; D017239:Paclitaxel; D002166:Camptothecin