Biodegradable block copolymers for delivery of proteins and water-insoluble drugs

Gaylen M. Zentner, Ramesh Rathi, Chung Shih, James C. McRea, Min Hyo Seo, Hunseung Oh, B. G. Rhee, Jiri Mestecky, Zina Moldoveanu, Michael Morgan, Steve Weitman

Research output: Contribution to journalArticle

463 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)203-215
Number of pages13
JournalJournal of Controlled Release
Volume72
Issue number1-3
DOIs
StatePublished - May 14 2001

Keywords

  • Biodegradable
  • Controlled release
  • Copolymers
  • Paclitaxel
  • Proteins
  • Thermal gels

ASJC Scopus subject areas

  • Pharmaceutical Science

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    Zentner, G. M., Rathi, R., Shih, C., McRea, J. C., Seo, M. H., Oh, H., Rhee, B. G., Mestecky, J., Moldoveanu, Z., Morgan, M., & Weitman, S. (2001). Biodegradable block copolymers for delivery of proteins and water-insoluble drugs. Journal of Controlled Release, 72(1-3), 203-215. https://doi.org/10.1016/S0168-3659(01)00276-0