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

Abstract

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