Novel geometry type of nanocarriers mitigated the phagocytosis for drug delivery

J Control Release. 2011 Aug 25;154(1):84-92. doi: 10.1016/j.jconrel.2011.04.023. Epub 2011 Apr 30.

Abstract

Target geometry for mitigating phagocytosis has garnered considerable attention recently in the drug delivery field. This study examined nanoparticles (NPs) with same volume but different shapes, namely, spherical NPs (SNPs) and hexagonal nanoprisms (HNPs), and analyzed their behaviors in vitro and in vivo. These NPs were constructed with a multifunctional block copolymer component, mPEG-b-P(HEMA-co-histidine-PLA). Geometry of SNPs and HNPs was controlled by adjusting copolymer properties and particle size was controlled by adjusting formulation parameters. Nanoparticle morphology had no effect in mitigating phagocytosis when NP size was 70 nm; however, morphology had a significant effect when NP size was 120 nm. The radioactivity-time curves for (99m)Tc-labeled NPs, fitted by the two-compartment pharmacokinetic model, show that the prolonged plasma distribution half-life of HNPs is indicative in the bloodstream. The in vitro and in vivo studies reveal that dual stealth characteristics, pegylation and hexagonal prism structure, of nanocarriers can be adopted in clinical application for safe and efficient delivery of cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry*
  • Drug Carriers / pharmacokinetics
  • Flow Cytometry
  • Half-Life
  • HeLa Cells
  • Humans
  • Macrophages, Alveolar / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Microscopy, Confocal
  • Models, Molecular
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Particle Size
  • Phagocytosis / physiology*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Polyethylene Glycols / pharmacokinetics
  • Polymethacrylic Acids / chemical synthesis
  • Polymethacrylic Acids / chemistry*
  • Polymethacrylic Acids / pharmacokinetics
  • Surface Properties
  • Xenograft Model Antitumor Assays

Substances

  • Drug Carriers
  • Polymethacrylic Acids
  • methoxy poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate)-co-histidine-poly(lactide)
  • Polyethylene Glycols