Incorporation of PVMMA to PLGA MS enhances lectin grafting and their in vitro activity in macrophages

Int J Pharm. 2010 Dec 15;402(1-2):165-74. doi: 10.1016/j.ijpharm.2010.10.006. Epub 2010 Oct 8.

Abstract

Attachment of lectins, especially those that are recognized and bounded by macrophages and other antigen presenting cells onto biodegradable microspheres surface, may serve as support for a wide variety of applications. The aim of this work was: (1) to prepare microspheres (MS) based on two biodegradable copolymers, poly (lactide-co-glicolide) acid (PLGA) and poly[(methyl vinyl ether)-co-(maleic anhydride)] (PVMMA) with their surface functionalized with Concanavalin A (Con A) and, (2) to evaluate their behaviour in macrophage culture. The incorporation of PVMMA was studied in order to augment the lectin coupling efficiency. MS were obtained by spray-drying and bovine serum albumin (BSA) was loaded as protein model. Particles were characterized for size, morphology, surface charge, entrapment efficiency, FTIR, in vitro protein release and conjugation efficiency. Finally, functionalized MS were tested in vitro with raw 264.7 murine macrophages (Mф) in terms of cytotoxicity, phagocytosis, nitric oxide (NO) production, and oxygen consumption. Conjugated Con A microspheres showed increased grafting efficiency up to four times compared to PLGA alone. The retention of Con A after coupling was confirmed by desorption studies. The attachment of Con A to microspheres induced oxygen consumption, increased phagocytosis efficiency and even NO production by macrophages. The results suggest that Con A and possibly, other lectins, grafted onto PLGA-PVMMA microspheres may serve as potential adjuvants by modulating protein delivery and macrophage activation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Line
  • Concanavalin A / chemistry
  • Drug Carriers / chemistry
  • Lectins / chemistry*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Maleates / chemistry*
  • Mice
  • Microspheres
  • Nitric Oxide / biosynthesis
  • Oxygen Consumption / drug effects
  • Phagocytosis / drug effects
  • Polyethylenes / chemistry*
  • Polyglactin 910 / chemistry*
  • Serum Albumin, Bovine / administration & dosage*
  • Serum Albumin, Bovine / chemistry

Substances

  • Drug Carriers
  • Lectins
  • Maleates
  • Polyethylenes
  • Concanavalin A
  • Serum Albumin, Bovine
  • Nitric Oxide
  • Polyglactin 910
  • poly(methyl vinyl ether-co-maleic anhydride)