Design of Tranilast-Loaded Cation-Type Contact Lens for Sustainable Ocular Drug Delivery

Abstract

Objectives: This study evaluated the design of a sustained-release contact lens (CL) device loading tranilast (TRA) and determined the usefulness of these CLs in Japanese albino rabbits. Methods: The sustainable CLs in this study were prepared by combining three CLs with different water contents and soaking methods under high-pressure and high-temperature using an autoclave method (AC-method). Results: Both the CLs prepared with the conventional soaking method (stir-method) and AC-methods were transparent in all three types of CLs. The loaded TRA contents in the CLs when using the AC-method were higher than those prepared using the stir-method for all three types of CLs. TRA contents were also higher when loaded into the cation-type lenses as compared to the other lenses. Moreover, the sustainable release of TRA from the TRA-loaded cation-type CL using the AC-method was significantly higher than those found for the other CLs. No corneal wounds were observed in any of the rabbits given the three types of TRA-loaded CLs for 7 days. Furthermore, the TRA-loaded CL sustainably released TRA into the lacrimal fluid in the rabbit. Conclusions: The TRA-loaded CL prepared using the AC-method overcame the limitations normally associated with the stir-method, such as the high burst release and low drug uptake.

Keywords: autoclave; cation; contact lenses; lacrimal fluid; tranilast.

Figure 1

Image of digital (A), microscope (B), SEM (C), and particle size distribution (D) of the TRA suspensions. The particle size of the TRA suspensions was approximately 15–200 µm.

Figure 2

Digital image of the TRA-loaded CLs prepared using the stir- or AC-methods. There were three types of CLs used (non-ion-, anion-, and cation-type). The scale bar in the lower right corner of the photograph represents 2 mm. The TRA-loaded CLs prepared using the stir- and AC-methods were transparent in all three types of the CLs.

Figure 3

Total TRA contents for the TRA-loaded CLs prepared using the stir- (A) and AC-methods (B). There were three types of CLs used (non-ion-, anion-, and cation-type) (n = 3). * p < 0.05 vs. non-ion for each category. ^# p < 0.05 vs. anion for each category. The TRA contents were strongly loaded into the cation-type CL as compared to the other types of the CLs. Moreover, the loaded TRA contents in the CLs when using the AC-method were significantly higher than those found for the stir-method for all three types of CLs.

Figure 4

Changes in release profile of the TRA from the TRA-loaded CLs that used the stir- (A) and AC-methods (B). n = 3. * p < 0.05 vs. non-ion for each category. ^# p < 0.05 vs. anion for each category. The TRA in the cation-type CLs prepared when using the AC-method exhibited a sustained-release from all three types of the CLs. Moreover, the sustained-release of the TRA from the cation-type CLs that were prepared using the AC-method was significantly higher than that found for the other CLs.

Figure 5

Corneal toxicity in the rabbits given the TRA-loaded CLs that were prepared using the AC-method. (A) Images of the eyes of the rabbits that were given the three types of the TRA-loaded CLs. The CLs were applied for 2 h. (B) Evaluation of the corneal wounds in the rabbits given the three types of the TRA-loaded CLs were performed using fluorescein. The CLs were repetitively applied to the rabbits for 8 h a day for 7 days, with the corneal wounds then subsequently monitored. There were three types of CLs used (non-ion-, anion-, and cation-type). There were no corneal wounds observed for any of the three types of the TRA-loaded CLs.

Figure 6

Profile (A) and AUC_LF (B) of TRA in the lacrimal fluid after the application of the three types of the TRA-loaded CLs prepared using the AC-method. There were three types of CLs used (non-ion-, anion-, and cation-type), with the TRA loaded to CLs using the AC-method. n = 5. * p < 0.05 vs. non-ion for each category. ^# p < 0.05 vs. anion for each category. The TRA-loaded CLs exhibited a sustained-release of TRA to the lacrimal fluid, with the TRA concentration in the lacrimal fluid the highest in the cation-type of the TRA-loaded CLs.