Evaluation of the levofloxacin release characters from a rabbit foldable capsular vitreous body

Abstract

The authors have manufactured a novel rabbit foldable capsular vitreous body (FCVB). The aim of this study was to determine whether this rabbit FCVB can release levofloxacin in vitro and in vivo, and to evaluate the release characteristics. In vitro, the rabbit FCVB with levofloxacin 500 μg/mL was immersed in cups of modified Franz diffusion cells. Following this, 200 μL of liquid was aspirated at intervals from 10 minutes to 24 hours. In vivo, the FCVB with levofloxacin was implanted into the right eyes of five rabbits. After implantation, the aqueous humor was aspirated on days 1, 7, 14, 28, and 56. The levofloxacin concentrations in the cups and aqueous humor samples were detected by high-performance liquid chromatography–tandem mass spectrometry. The FCVB was observed under a scanning electron microscope. The results showed that the released levofloxacin was stabilized at 20 ng/mL at time points from 10 minutes to 24 hours in vitro. In vivo, levofloxacin concentrations in the aqueous humor were 132, 50, 39, 11, and 15 ng/mL on days 1, 7, 14, 28, and 56, respectively. In the FCVB capsules, 300 nm apertures were observed. These results suggest the rabbit FCVB released levofloxacin stably in vitro and sustainably in vivo. This study provides a novel combined approach, with the FCVB as a vitreous substitute and drug delivery system for the treatment of bacterial endophthalmitis.

A Preliminary Study to Treat Severe Endophthalmitis via a Foldable Capsular Vitreous Body with Sustained Levofloxacin Release in Rabbits

“…In our previous study, we reported that the release values of the FCVB with 500 lg/mL levofloxacin in normal eyes were 132, 50, 39, 11, and 15 ng/mL on days 1, 7, 14, 28, and 56, respectively. 26 In our study, we found that the values with 625 lg/mL levofloxacin in endophthalmitis eyes were 42, 31, 12.5, 5.6, 2.5, and 0.6 ng/mL on days 1, 3, 5, 10, 20, and 30, respectively. Although similar release tendency appeared, release values in normal eyes were bigger than those in endophthalmitis ones probably due to inflammation.…”

“…42 Therefore, FCVB results also may have implications in the treatment of important retinal diseases that need drug and vitreous substitutes, such as age-related macular degeneration, proliferative vitreoretinopathy, and proliferative diabetic retinopathy. This work, along with our other reports regarding the FCVB, [21][22][23][24][25][26][27][28][29][30]42 give an example of how to make the product from bench to bedside, including idea, craft, animal model, producing standard, technical reports from government, clinical trails (exploratory, multiple centers), and marketing. Based on this study, we will apply for a new clinical trial to test the combined function of FCVB.…”

“…19,20 In our previous studies, we proposed a new strategy to fabricate a vitreous substitute with a novel foldable capsular vitreous body (FCVB). [21][22][23][24][25][26] The FCVB, made with modified liquid silicone rubber, consists of a thin, vitreous-like capsule finely mimicked by computer, and a tube-valve system. After the FCVB capsule is folded and implanted in the vitreous cavity, a balanced salt solution (BSS) and/or therapeutic drugs then can be injected into the capsule, and the capsule inflated to support the retina.…”

“…24 Moreover, we determined that the human FCVB could release levofloxacin in vitro, 25 as well as the rabbit FCVB could release levofloxacin in vitro and vivo. 26 Here, we tested further whether the FCVB could serve as a vitreous substitute and DDS in the rabbit endophthalmitis model.…”

Preliminary Study on Retinal Vascular and Oxygen-related Changes after Long-term Silicone Oil and Foldable Capsular Vitreous Body Tamponade

“…In the FCVB capsule, mini-apertures of 300 nm were detected via the scanning electron microscope1755 and in our previous studies, we noted that these mini-apertures can slowly release micromolecular substances, such as dexamethasone sodium phosphate56, 5-fluorouracil (5-Fu)57 and siRNA-PKCα55. Therefore, the thin capsule membrane was highly oxygen permeable due to the mini-apertures.…”