Micelle carriers based on macrogol 15 hydroxystearate for ocular delivery of terbinafine hydrochloride: In vitro characterization and in vivo permeation.

ABSTRACT

Non-ionic surfactant micelles are helpful for improving the diffusion of topically delivered drugs through the cornea. This study aimed to develop terbinafine hydrochloride (TH)-loaded micelles based on a soft non-ionic surfactant-macrogol 15 hydroxystearate (HS 15) and to investigate their in vivo cornea permeation. Briefly, 0.25% TH-loaded HS 15 micelles (TH-HNMs) were developed using a simple co-solvent method. Characterization of the TH-HNMs by Zetasizer and transmission electron microscopy (TEM) revealed that the spherical and discrete micellar droplets with a small size (13.22±0.73nm) and an electrically neutral surface (-2.15±0.39mV) were achieved. The drug entrapment efficiency of TH-HNMs was almost 100%. The release of TH from the micelles was pH dependent. 93.2±3.4% of encapsulated TH was released from the micelles in the PBS at pH5.0 within 6h, but only 0.122±0.020% of encapsulated TH was released in the PBS at pH7.4 within the same release time. TH-HNMs possessed good physical stability in the pH neutral medium (pH7.0).No obvious irritations were observed in rabbit eyes after ocular instillation of TH-HNMs. The in vivo corneal permeation study revealed that the TH-HNMs can penetrate into the corneal epithelium quickly and efficiently in mouse eyes. Good permeability was also noted in the stroma of mouse corneas with de-epithelialization. Compared with the TH oily solution, TH-HNMs delivered considerably increased levels of TH into rabbit corneas with or without de-epithelialization. In conclusion, the easily prepared, small, physically stable and biocompatible TH-HNMs with good ocular bioavailability hold great promise as an efficient carrier for topical ocular delivery of TH.