Intraocular pressure changes: an important determinant of the biocompatibility of intravitreous implants

PLoS One. 2011;6(12):e28720. doi: 10.1371/journal.pone.0028720. Epub 2011 Dec 14.

Abstract

Background: In recent years, research efforts exploring the possibility of using biomaterial nanoparticles for intravitreous drug delivery has increased significantly. However, little is known about the effect of material properties on intravitreous tissue responses.

Principal findings: To find the answer, nanoparticles made of hyaluronic acid (HA), poly (l-lactic acid) (PLLA), polystyrene (PS), and Poly N-isopropyl acrylamide (PNIPAM) were tested using intravitreous rabbit implantation model. Shortly after implantation, we found that most of the implants accumulated in the trabecular meshwork area followed by clearance from the vitreous. Interestingly, substantial reduction of intraocular pressure (IOP) was observed in eyes implanted with particles made of PS, PNIPAM and PLLA, but not HA nanoparticles and buffered salt solution control. On the other hand, based on histology, we found that the particle implantation had no influence on cornea, iris and even retina. Surprisingly, substantial CD11b+ inflammatory cells were found to accumulate in the trabecular meshwork area in some animals. In addition, there was a good relationship between recruited CD11b+ cells and IOP reduction.

Conclusions: Overall, the results reveal the potential influence of nanoparticle material properties on IOP reduction and inflammatory responses in trabecular meshwork. Such interactions may be critical for the development of future ocular nanodevices with improved safety and perhaps efficacy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acrylic Resins / metabolism
  • Animals
  • Biocompatible Materials / pharmacology*
  • CD11b Antigen / metabolism
  • Cornea / drug effects
  • Cornea / pathology
  • Eye, Artificial*
  • Fluorescein-5-isothiocyanate
  • Implants, Experimental*
  • Inflammation / pathology
  • Intraocular Pressure / drug effects
  • Intraocular Pressure / physiology*
  • Intravitreal Injections
  • Iris / drug effects
  • Iris / pathology
  • Kidney / drug effects
  • Kidney / pathology
  • Nanoparticles / administration & dosage
  • Prosthesis Implantation
  • Rabbits
  • Trabecular Meshwork / metabolism
  • Trabecular Meshwork / pathology
  • Vitreous Body / drug effects*
  • Vitreous Body / physiology*

Substances

  • Acrylic Resins
  • Biocompatible Materials
  • CD11b Antigen
  • poly-N-isopropylacrylamide
  • Fluorescein-5-isothiocyanate