Paclitaxel Associated With Lipid Nanoparticles as a New Antiscarring Agent in Experimental Glaucoma Surgery

Invest Ophthalmol Vis Sci. 2016 Mar;57(3):971-8. doi: 10.1167/iovs.15-18671.

Abstract

Purpose: To investigate the effects of paclitaxel associated with lipid nanoemulsions (LDE-PTX) on postoperative scarring in rabbits undergoing trabeculectomy.

Methods: Thirty-four rabbits that underwent trabeculectomy were allocated to four groups: LDE-PTX/SC (n = 9), treated with LDE-PTX (1.5 mg, intraoperative subconjunctival injection); LDE-PTX/IV (n = 9), treated with LDE-PTX (4 mg/kg per day intravenously) at the end of the surgery and once per week for 3 weeks; MMC (n = 9), treated with intraoperative 0.4 mg/mL mitomycin-C for 3 minutes; and control group (CTL, n = 7), without treatment. Bleb characteristics and IOP were evaluated over 4 weeks. Animals were killed on day 28. Histologic analyses were performed to assess the amount of scarring and toxicity to the conjunctiva and ciliary body.

Results: Groups were similar with respect to IOP and anterior chamber depth during the 28-day observation period. The LDE-PTX/SC, LDE-PTX/IV, and MMC groups showed greater bleb height than CTL on days 14 and 21 (P < 0.001). The LDE-PTX/SC, LDE-PTX/IV, and MMC groups showed longer bleb survival time than CTL (P < 0.001). The LDE-PTX/SC, LDE-PTX/IV, and MMC groups were equally effective in reducing fibrosis (P < 0.001), number of blood vessels (P < 0.001), and chronic inflammatory cells (P < 0.01) at the surgical site. However, LDE-PTX/SC and LDE-PTX/IV treatments had lower conjunctival (P < 0.001) and ciliary body toxicity (P < 0.01), compared with MMC.

Conclusions: The LDE-PTX/SC was effective in reducing the scarring process following trabeculectomy to the same extent as MMC, but with considerably less toxicity to the conjunctiva and ciliary body. The LDE-PTX/IV was somewhat less effective than LDE-PTX/SC or MMC, but could have potential as a postoperative adjuvant treatment. Therefore, the LDE-PTX preparation in both administration routes may offer promising options for wound-healing modulation in the surgical treatment of glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Cicatrix / diagnosis
  • Cicatrix / etiology
  • Cicatrix / prevention & control*
  • Conjunctiva
  • Disease Models, Animal
  • Drug Carriers
  • Follow-Up Studies
  • Glaucoma / physiopathology
  • Glaucoma / surgery*
  • Injections
  • Intraocular Pressure
  • Lipids
  • Male
  • Nanoparticles / administration & dosage*
  • Paclitaxel / administration & dosage*
  • Postoperative Complications / diagnosis
  • Postoperative Complications / etiology
  • Postoperative Complications / prevention & control*
  • Rabbits
  • Trabeculectomy / adverse effects*

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Lipids
  • Paclitaxel