Molecular design of polyvinylpyrrolidone-conjugated interleukin-6 for enhancement of in vivo thrombopoietic activity in mice

J Control Release. 2000 Sep 3;68(3):335-41. doi: 10.1016/s0168-3659(00)00249-2.


Functional polyvinylpyrrolidone (PVP) was synthesized as a novel polymeric modifier for polymer-conjugated cytokines, and its efficiency and applicability as a drug delivery system (DDS) were evaluated. PVP with a carboxyl group at one end of the main chain was prepared by radical polymerization (M(n): 6000, M(w)/M(n): 1.14) with the aid of 4,4'-azobis(4-cyanovaleric acid) as a radical initiator and 3-mercaptopropionic acid as a transfer agent. Interleukin-6 (IL-6) was covalently conjugated via the formation of amino bonds between the lysine amino groups of IL-6 and PVP. PVP-conjugated IL-6, in which 60% of the fourteen lysine amino groups of IL-6 were estimated to be coupled with PVP (M-PVP-IL-6), showed more than 50-fold greater thrombopoietic potency in vivo than native IL-6. No side effects, such as body weight loss, were observed in the M-PVP-IL-6 treated mice. These results indicate that PVP as a polymeric modifier is a promising DDS for clinical application of cytokines and other therapeutic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / drug effects*
  • Body Weight / drug effects
  • Interleukin-6 / administration & dosage*
  • Interleukin-6 / chemistry
  • Interleukin-6 / pharmacology*
  • Mice
  • Mice, Inbred C3H
  • Molecular Weight
  • Pharmaceutic Aids / chemistry*
  • Platelet Count
  • Povidone / chemistry*
  • Stimulation, Chemical
  • Structure-Activity Relationship


  • Interleukin-6
  • Pharmaceutic Aids
  • Povidone