| Part â… Fabrication of drug-loaded microspheres as sustained antibiotic releaser in haptics of intraocular lens and their in vitro anti-bacterial effectsObjective:We developed a novel drug-loaded microspheres by spraying and condensation that can be implanted into intraocular lens and sustain the release of antibiotics. The physicochemical property and in vitro anti-bacterial effects of the novel IOL were assessed.Methods:Drug-loaded microspheres were developed by spraying and condensing the mixture of gatifloxacin and glyceryl tristearate. The microspheres were implanted into the intraocular lens by vacuum aspiration. The surface morphology and topography measurement of the microspheres, the haptics of the antibiotic-loaded and untreated IOLs were determined by a scanning electron microscope (SEM). XPS was used to analyze the elemental composition of the antibiotic-loaded IOLs and the untreated IOLs surfaces. The optical and physical properties of the antibiotic-loaded IOLs were assessed. The toxicity of the novel IOL was tested by CCK-8. High pressure liquid chromatography (HPLC) and LIVE/DEAD BacLight Bacterial vitality kit were used to test the in vitro antibiotic release kinetics and efficacy of antibiotic function.Results:Compared with the haptics of the untreated IOLs group, SEM revealed the circular holes with compact and slightly rough orbicular microspheres in the antibiotic-loaded IOLs. The survey XPS spectra of IOLs showed an increase in the peak intensity of Fls (P<0.05) in the antibiotic-loaded IOLs compared with the untreated IOLs. The diopers, modulation transfer function, spectral transmittance and endurance were qualified according to Chinese National Quality Test Standard of IOLs (YY-0290). The novel IOL was nontoxic according to CCK-8. The in vitro results showed sustained sufficient antibiotic concentration (above MIC for most common bacteria related to endophthalmitis) for over two weeks of the antibiotic-loaded IOLs. The gatifloxacin-loaded IOLs also showed obvious anti-bacterial efficacy.Conclusions:The study of the antibiotic-loaded IOLs demonstrates the successful loading of microspheres with antibiotic into the intraocular lens. It is feasible to deliver sufficient and effective antibiotic without affecting the optical and physical properties of the IOLs to prevent the postsurgical infective endophthalmitis. Part II Prevention of endophthalmitis by antibiotic-loaded IOLs in animal modelObjective:To assess the efficacy and safety of novel antibiotic microspheres loaded IOL in preventing endophthalmitis.Methods:The novel IOLs were fabricated by aspirating gatifloxacin and glyceryl tristearate loaded microspheres into the intraocular lens. Fifteen colored rabbits (15eyes) were randomly divided into three group, operated on with phacoemulsification and implanted into routine hydrophobic Polyacrylate IOL (group A, n=5, OD), routine hydrophobic Polyacrylate IOL (group B, n=5, OD) and microspheres loaded IOL (group C, n=5, OD). No bacteria was injected into the eyes in group A while in group B and C30μl bacteria was injected into anterior chamber24hours after surgery. No antibiotic ophthalmic solution was applied after the phacoemulsification. One day before the operation, the rabbits were examined and postoperative follow-up was done on the1st,2nd,3rd,4th,8th,15th,22nd and29th days after the operation. Rabbits were observed by slitlamp examination to evaluate eye lids, conjunctiva, cornea, anterior chamber, iris, pupil and IOL. The aqueous humor was extracted once opacification, exudation or empyema occurred. Gram stain, bacterial culture and mass spectrometry with Bruker Daltonik MALDI Biotyper were applied on the samples. Eyes with endophthalmitis were extracted8th day after surgery and the other samples were obtaind one month after the operation. Histological section of the eyes were prepared by paraffin embedding and stained with HE stain to observe the structure of cornea, iris, retina and compare among the groups. Results:The microspheres loaded IOL and routine hydrophobic Polyacrylate IOL could be successfully implanted into the capsule without anterior chamber inflammation. No preoperatively ophthalmic inflammation could be observed among the three group. On the1st day after operation, the inflammatory results among the groups were not statistically significant before the injection of Staphylococcus epidermidis. After the injection (the2nd day after the surgery), the difference between group B and group A, group B and group C were statistically significant. No statistical difference could be observe between group A and group C. Obvious ocular inflammation occurred in the rabbits of group B and Staphylococcus epidermidis was confirmed by staining, bacterial culture and mass spectrometry of the aqueous humor. No ocular inflammation occurred in group C. The paraffin section showed regular cornea, iris and retina in group A and group C while edematous cornea, tumid and congestive iris, and retina with lots of inflammatory cells and fibrin exudation in group B.Conclusions:The novel antibiotic microspheres loaded IOL was effective and safe to prevent endophthalmitis in animal model. |
