scholarly journals Comparison of cytotoxicity of fluoroquinolone antimicrobial eye drops and its effect on their bioavailability

2017 ◽  
Vol 10 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Tamara S Hintuba ◽  
Yuri V Takhtaev ◽  
Igor N Okolov ◽  
Vera A Motyleva ◽  
Roman B Shlyakman
Keyword(s):  
Corneal Epithelium ◽  
Benzalkonium Chloride ◽  
High Yield ◽  
Eye Drops ◽  
Cytostatic Effect ◽  
Cytotoxic Potential ◽  
The Russian Federation ◽  
Chamber Fluid ◽  
Preservative Free

In addition to the breadth of activity of antibacterial medications as well as to their pharmacokinetic and pharmacodynamic properties, their safety and bioavailability represent an important aspect. Currently, there is no consensus on fluoroquinolone toxicity. The aim of the present study was to compare the total cytotoxic effect on corneal epithelium and bioavailability of three antibacterial fluoroquinolone eye drops, registered in the Russian Federation: 1) Oftaquix™ (levofloxacin 5 mg/ml; preservative benzalkonium chloride (BAC) 0.05 mg/ml; produced by Santen Oy, Finland), hereafter “levofloxacin (original)”; 2) Signicef® (levofloxacin 5 mg/ml; preservative BAC 0.1 mg/ml; produced by Sentiss Pharma Pvt. Ltd., India), hereafter “levofloxacin (generic)”; 3) Vigamox® (moxifloxacin® 5 mg/ml; preservative-free; produced by Alcon Laboratories, Inc., USA) hereafter “moxifloxacin” - using in vivo methods and determining the possible effect of preservative presence (in different concentration) or of its absence on reaching the minimal threshold concentrations of the antibiotic in the anterior chamber fluid, using the high-yield liquid chromatography combined with mass-spectrometric detection. The study showed that tested antibacterial medications could exert a cytostatic effect on the corneal epithelium at in vivo conditions and differ in their cytotoxic potential. Benzalkonium chloride presence in Signicef in a concentration twice as high than that of the main medication (Oftaquix) causes a proven by confocal microscopy effect on the corneal epithelium, and this may influence the bioavailability of the medication.

scholarly journals Kynurenic Acid Accelerates Healing of Corneal Epithelium In Vitro and In Vivo

2021 ◽  
Vol 14 (8) ◽  
pp. 753
Author(s):  
Anna Matysik-Woźniak ◽  
Waldemar A. Turski ◽  
Monika Turska ◽  
Roman Paduch ◽  
Mirosław Łańcut ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Corneal Epithelium ◽  
Kynurenic Acid ◽  
Pharmaceutical Products ◽  
Corneal Epithelial Cell ◽  
Eye Drops ◽  
Conjunctival Epithelium ◽  
Corneal Erosion

Kynurenic acid (KYNA) is an endogenous compound with a multidirectional effect. It possesses antiapoptotic, anti-inflammatory, and antioxidative properties that may be beneficial in the treatment of corneal injuries. Moreover, KYNA has been used successfully to improve the healing outcome of skin wounds. The aim of the present study is to evaluate the effects of KYNA on corneal and conjunctival cells in vitro and the re-epithelization of corneal erosion in rabbits in vivo. Normal human corneal epithelial cell (10.014 pRSV-T) and conjunctival epithelial cell (HC0597) lines were used. Cellular metabolism, cell viability, transwell migration, and the secretion of IL-1β, IL-6, and IL-10 were determined. In rabbits, after corneal de-epithelization, eye drops containing 0.002% and 1% KYNA were applied five times a day until full recovery. KYNA decreased metabolism but did not affect the proliferation of the corneal epithelium. It decreased both the metabolism and proliferation of conjunctival epithelium. KYNA enhanced the migration of corneal but not conjunctival epithelial cells. KYNA reduced the secretion of IL-1β and IL-6 from the corneal epithelium, leaving IL-10 secretion unaffected. The release of all studied cytokines from the conjunctival epithelium exposed to KYNA was unchanged. KYNA at higher concentration accelerated the healing of the corneal epithelium. These favorable properties of KYNA suggest that KYNA containing topical pharmaceutical products can be used in the treatment of ocular surface diseases.

scholarly journals Effects of Eye Drops Containing Hyaluronic Acid-Nimesulide Conjugates in a Benzalkonium Chloride-Induced Experimental Dry Eye Rabbit Model

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1366
Author(s):  
Tzu-Yang Chen ◽  
Ching-Li Tseng ◽  
Chih-An Lin ◽  
Hua-Yang Lin ◽  
Parthiban Venkatesan ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Dry Eye ◽  
Goblet Cell ◽  
Corneal Epithelium ◽  
Benzalkonium Chloride ◽  
Immunofluorescent Staining ◽  
Prolonged Treatment ◽  
Eye Drops ◽  
Cell Recovery ◽  
Anti Inflammatory

Dry eye syndrome (DES) is a common ocular disease worldwide. Currently, anti-inflammatory agents and immunosuppressive drugs, such as cyclosporine A, have been widely used to treat this chronic condition. However, the multifactorial etiology of DES, poor tolerance, low bioavailability, and prolonged treatment to response time have limited their usage. In this study, nimesulide, a cyclooxygenase (COX)-2 selective inhibitor, was conjugated with hyaluronic acid (HA), and the HA-nimesulide conjugates were expected to increase the solubility and biocompatibility for alleviating the DES in the benzalkonium chloride (BAC)-induced goblet cell-loss dry eye model. The therapeutic efficacy of HA-nimesulide was assessed using fluorescein staining, goblet cell density by conjunctival impression cytology, and histology and immunohistochemistry of corneal tissues. Compared to commercial artificial tears and Restasis®, the HA-nimesulide conjugates could promote goblet cell recovery and enhance the regeneration of the corneal epithelium. Importantly, immunofluorescent staining studies demonstrated that the HA-nimesulide conjugates could decrease the number of infiltrating CD11b-positive cells after two weeks of topical application. In the anti-inflammatory test, the HA-nimesulide conjugates could inhibit the production of pro-inflammatory cytokines and prostaglandin E2 (PGE2) in the lipopolysaccharide (LPS)-stimulated Raw 264.7 cell model. In conclusion, we demonstrated that HA-nimesulide conjugates had anti-inflammatory activity, and promoted goblet cell recovery and corneal epithelium regeneration when used as topical eye drops; accordingly, the HA-nimesulide conjugates could potentially be effective for the treatment of DES.

scholarly journals Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops

2021 ◽  
Vol 6 (1) ◽  
pp. e000892
Author(s):  
Olivia Müllertz ◽  
Anne Hedengran ◽  
Zaynab Ahmad Mouhammad ◽  
Josefine Freiberg ◽  
Richárd Nagymihály ◽  
...  
Keyword(s):  
Surface Tension ◽  
Physicochemical Properties ◽  
Benzalkonium Chloride ◽  
Ph Value ◽  
Acute Exposure ◽  
Eye Drops ◽  
Drop Mass ◽  
Mucin Release ◽  
The Impact ◽  
Preservative Free

ObjectiveTo investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.Methods and analysisPrimary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured.ResultsAfter application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p<0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m).ConclusionPF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.

scholarly journals Ocular Tolerability of Preservative-Free Tafluprost and Latanoprost: in vitro and in vivo Comparative Study

2016 ◽  
Vol 10 (1) ◽  
pp. 146-153 ◽  
Author(s):  
Yoshihiko Esaki ◽  
Atsushi Shimazaki ◽  
Pertti Pellinen
Keyword(s):  
T Cells ◽  
Significant Loss ◽  
Eye Drops ◽  
Negative Effects ◽  
Ocular Irritation ◽  
Rabbit Eye ◽  
Ocular Tolerability ◽  
Preservative Free

Objective: Detrimental effects of the preserved prostaglandin analogs (PGAs) have been thoroughly documented in the published literature. The current work studied two preservative-free (PF) prostaglandin eye drops: PF tafluprost and PF latanoprost. The aim of the study was to compare these two PF formulations in vitro for viability of the human corneal epithelial (HCE-T) cells and in vivo for ocular tolerability of the rabbit eye. Method: Viability of the HCE-T cells was measured by the MTS assay. The SV40-immortalized HCE-T cells were exposed to 100 µL of the drug solutions (at their commercial concentrations) or the culture medium. Ocular irritation was evaluated after repeated instillation of the drug solutions in Japanese white rabbits (Kbl:JW). Results: A significant loss of HCE-T cell viability was observed in vitro immediately after the exposure to PF latanoprost formulation but not immediately after the exposure to PF tafluprost formulation. Congruently, PF latanoprost induced in vivo more irritation on the rabbit eye than PF tafluprost. Conclusion: Comparing these two PF formulations in vitro and in vivo, it is considered that ocular tolerability of PF tafluprost is better than PF latanoprost. Taking into account the composition of these two PF PGA formulations, the solubilizing agent macrogolglycerol hydroxystearate 40 (MGHS40) contained in PF latanoprost formulation is a plausible cause for the negative effects.

A microengineered human corneal epithelium-on-a-chip for eye drops mass transport evaluation

Lab on a Chip ◽  
2018 ◽  
Vol 18 (11) ◽  
pp. 1539-1551 ◽  
Author(s):  
Devasier Bennet ◽  
Zachary Estlack ◽  
Ted Reid ◽  
Jungkyu Kim
Keyword(s):  
Mass Transport ◽  
Corneal Epithelium ◽  
Drug Testing ◽  
Eye Drops ◽  
Physiological Conditions ◽  
Human Corneal Epithelium

A microengineered human corneal epithelium-on-a-chip is developed to mimic in vivo anatomical and physiological conditions for topical ophthalmological drug testing.

scholarly journals A comparative evaluation of antimicrobial eye drops cytotoxicity

2015 ◽  
Vol 8 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Olga Igorevna Aleksandrova ◽  
Igor Nikolaevich Okolov ◽  
Yuri Victorovich Takhtaev ◽  
Juliya Igorevna Khorolskaya ◽  
Tamara Slavikovna Hintuba ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Comparative Evaluation ◽  
Cytotoxic Effect ◽  
Cultured Cells ◽  
Eye Drops ◽  
Cytostatic Effect ◽  
Cytotoxic Potential ◽  
Cytotoxic Effects

In addition to the spectrum of antibacterial activity of antimicrobial medicines and their pharmacokinetic and pharmacodynamic properties, their safety is also an important issue. Currently, there is no consensus on the fluoroquinolone toxicity. The purpose of this study was to compare in vitro the overall cytotoxic effect of six antibacterial fluoroquinolone eye drops: 1. Cipromed™ (ciprofloxacin 0.3 %; Sentiss Pharma Pvt. Ltd., India); 2. Floxal™ (ofloxacin 0.3 %; Dr. Gerhard Mann, Chem.-Pharm. Fabrik GmbH, Germany); 3. Oftaquix™ (levofloxacin 0.5 %; Santen Oy, Finland); 4. Signicef® (levofloxacin 0.5 %; Sentiss Pharma Pvt. Ltd., India); 5. Vigamox® (moxifloxacin 0.5 %; Alcon Laboratories, Inc., USA); 6. Zymar® (gatifloxacin 0.3 %; Allergan Sales LLC, USA). The study showed the possibility of using cultured cells for comparative evaluation of cytotoxic effects of various ophthalmic preparations. We found that tested antimicrobial medicines may have a cytostatic effect in vitro and differ in their cytotoxic potential.

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