Cloxacillin nanostructured formulation for the treatment of bovine keratoconjunctivitis (original) (raw)
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International Journal of Pharmaceutics, 2020
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Design of Topical Ocular Ciprofloxacin Nanoemulsion for the Management of Bacterial Keratitis
Pharmaceuticals, 2021
Bacterial keratitis (BK) is a critical ocular infection that can lead to serious visual disability. Ciprofloxacin (CIP), moxifloxacin (MOX), and levofloxacin (LFX) have been accepted as monotherapies by the US Food and Drug Administration for BK treatment. CIP is available commercially at 0.3% w/v concentration as an ophthalmic solution and as an ointment for ocular delivery. Because of solubility issues at physiological pH, CIP precipitation can occur at the corneal surface post instillation of the solution dosage form. Consequently, the ocular bioavailability of CIP is reduced. The ointment dosage form is associated with side effects such as blurred vision, itching, redness, eye discomfort, and eye dryness. This study aimed to design a CIP loaded nanoemulsion (NE; CIP-NE) to facilitate drug penetration into the corneal layers for improved therapeutic outcomes as well as to overcome the drawbacks of the current commercial ophthalmic formulations. CIP-NE formulations were prepared b...
Evaluation of nanoformulated therapeutics in an ex-vivo bovine corneal irritation model
nanoformulated natural proteins in ex-vivo bovine corneal alkali burn model. Methods: The bovine cornea obtained were subjected to the 0.5 N NaOH insult that induced alkali burn and inflammation as observed in the in vivo situation. The toxic effects of the nanoformulation were evaluated in the normal and insult induced cornea using histological analysis. Internalization studies were carried out using in vivo imaging and analysis (IVIS, PerkinElmer, USA). Results: The nanoformulations employed in this study showed no obvious changes in the integrity of the cornea. Further, improvements in the light transmittance and reduced inflammation were observed. The IVIS showed a dose dependant increase in the uptake of the nanoformulations with time. Conclusion: The nanoformulated bovine lactoferrin and SurR9-C84A (SR9) proteins evaluated in the ex vivo bovine corneal irritation model is the first of its kind, and we report here the non-toxic and therapeutic potential of these formulations for topical applications.
Journal of Pharmaceutical Sciences, 2019
The study was designed to fabricate the moxifloxacin nanostructured lipid carriers (MOX-NLCs) loaded in situ gel for opthalmic application to improve the corneal permeation and retention and also subside the toxic effect associated with intracameral injection of moxifloxacin in endophthalmitis treatment. Initially, Box-Behnken design was used to optimize the various factors significantly affecting the final formulation attributes. MOX-NLCs with particle size 232.1 ± 9.2 nm, polydispersity index 0.247 ± 0.031, zeta potential À16.3 ± 1.6 mV, entrapment efficiency 63.1 ± 2.4%, and spherical shape was achieved. The optimized MOX-NLCs demonstrated the Higuchi release kinetics with highest regression coefficient. Besides this, FTIR, differential scanning calorimetry, and X-ray diffraction results suggested that MOX had excellent compatibility with excipients. Furthermore, the results of ex-vivo permeation study demonstrated 2-fold higher permeation (208.7 ± 17.6 mg), retention (37.26 ± 2.83 mg), and flux (9.57 ± 0.73 mg/ cm 2 h) compared with free MOX in situ gel. In addition, MOX-NLCs exhibited normal corneal hydration and did not show any sign of structural damage to the corneal tissue as confirmed by histology. Therefore, the findings strongly suggest that MOX-NLCs in situ gel with higher permeation and retention can be a better alternative strategy to prevent and treat the endophthalmitis infection.
Eye & Contact Lens: Science & Clinical Practice, 2019
Background: OTX-101 (CEQUA™) is approved in the United States for treatment of keratoconjunctivitis sicca (KCS). This pooled analysis of 2 studies (phase 2b/3 and phase 3) evaluates the efficacy and safety of OTX-101 0.09% in the intent-to-treat (ITT) population and the subgroup of patients with a baseline Schirmer score less than 10 mm. Methods: In these randomized, multicenter, double-masked, vehiclecontrolled studies, patients received 1 drop of either OTX-101 or vehicle in both eyes twice daily. A Schirmer's test was performed at baseline and day 84/early discontinuation. Symptom Assessment iN Dry Eye (SANDE) scores and adverse events were monitored at each visit. Results: The pooled analysis included 523 and 525 patients randomized to OTX-101 0.09% and vehicle, respectively. In the ITT population, 16.6% of eyes receiving OTX-101 and 9.0% of eyes receiving vehicle showed a day 84 increase in Schirmer score $10 mm from baseline (P,0.0001). In the subgroup with Schirmer score less than 10 mm at baseline, 18.7% and 10.2% of eyes receiving OTX-101 and vehicle, respectively, exhibited this outcome (P¼0.0001). The mean (SD) percent change from baseline in global SANDE scores on day 84 in the ITT population was 229.0% (39.0%) and 230.4% (39.5%) for OTX-101 and vehicle groups, respectively. In the subgroup, the mean (SD) percent change was 227.3% (39.7%) and 231.4% (38.3%) for OTX-101 and vehicle groups, respectively. Adverse events were mostly mild to moderate. Conclusions: OTX-101 improved tear production compared with vehicle. Both OTX-101 and vehicle showed improved SANDE scores over baseline. OTX-101 was well tolerated in patients with KCS.
Gatifloxacin Loaded Nano Lipid Carriers for the Management of Bacterial Conjunctivitis
Antibiotics
Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization–probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug re...
Lomefloxacin HCl (LF) is a widely used fourthgeneration fluoroquinolone antibiotic. Like most drug solutions administered via ocular route, it is usually eliminated by eye protective mechanisms. Chitosan (CS) is a natural polysaccharide polymer with numerous advantages in ocular delivery with, antibacterial, and antifungal properties. The aims were to formulate and optimize LF nanosuspensions (NS) with enhanced antimicrobial activity and prolonged duration using ionic gelation technique. Formulation variables included drug load, CS concentration, crosslinker type (tripolyphosphate and sodium alginate), and concentration. Nanosuspension properties (particle size, zeta potential, polydispersity index, entrapment efficiency, drug release, and permeation through bovine cornea) were evaluated. The artificial neural networks (ANNs) model showed optimum entrapment efficiency of 70.63 % w/w, particle size of 176±0.28 nm, and zeta potential of 13.65 mV. Transmission electron microscopy illustrated the production of well-defined spherical nanoparticles. The nanosuspensions showed prolonged release of LF for more than 8 h and threefold increase in amount permeated through bovine cornea compared to drug solution. Improved antibacterial activity of the nanosuspension was noted where 2- and 3.5-fold decrease in minimum inhibitory concentration (MIC) of drug against Gram-positive and Gram-negative bacteria were observed, respectively. Twofold decrease in minimum bactericidal concentration (MBC) of drug nanosuspension against both types of bacteria was also demonstrated. Histopathological examination showed compatibility of optimized formulation with eye tissues in rabbit model. Therefore, model-optimized LF nanosuspension could be an ideal solution to ocular infections by virtue of their augmented activity, high compatibility, and improved permeability.
International Journal of Nanomedicine
The topically administered drugs through conventional delivery systems have low bioavailability. Henceforth, the present study was designed to prepare and optimize clarithromycin (CTM)-loaded chitosan nanoparticles (CHNPs) to demonstrate the efficacy against microorganisms. Methods: Clarithromycin-loaded chitosan nanoparticles (CTM-CHNPs) were prepared by ionotropic gelation method. The formulation was optimized by box-Behnken design using the formulation variables like CH (A), STPP concentration (B), and stirring speed (C). Their effects were evaluated on the independent variables like particle size (Y 1) and entrapment efficiency (Y 2). Further, CTM-CHNPs were evaluated for physicochemical parameters, invitro drug release, ex-vivo permeation, bioadhesive study, corneal hydration, histopathology, HET-CAM, and antibacterial study. Results: The optimized formulation (CTM-CHNPopt) showed the low particle size (152±5 nm), which is desirable for ocular delivery. It also showed high encapsulation (70.05%), zeta potential (+35.2 mV), and was found in a spherical shape. The drug release study revealed a sustained drug release profile (82.98±3.5% in 12 hours) with Korsmeyer peppas kinetic (R 2 =0.996) release model. It showed a 2.7-fold higher corneal permeation than CTMsolution. CHNPs did not exhibit any sign of damage to excised goat cornea, which is confirmed by hydration, histopathology, and HET-CAM test. It exhibited significant (P<0.05) higher antibacterial susceptibility than CTM-solution. Conclusion: The finding of the study concluded that CTM-CHNPs can be used for effective management of bacterial conjunctivitis by increasing the precorneal residence time.
Sustained Ocular Delivery of Ciprofloxacin Using Nanospheres and Conventional Contact Lens Materials
Investigative Ophthalmology & Visual Science, 2012
PURPOSE. To formulate conventional contact lenses that incorporate nanosphere-encapsulated antibiotic and demonstrate that the lenses provide for sustained antibacterial activity. METHODS. A copolymer composed of pullulan and polycaprolactone (PCL) was used to synthesize core-shell nanospheres that encapsulated ciprofloxacin. Bactericidal activity of the nanosphere-encapsulated ciprofloxacin (nanosphere/cipro) was tested by using liquid cultures of either Staphylococcus aureus or Pseudomonas aeruginosa. Nanosphere/cipro was then incorporated into HEMA-based contact lenses that were tested for growth inhibition of S. aureus or P. aeruginosa in liquid cultures inoculated daily with fresh bacteria. Lens designs included thin or thick lenses incorporating nanosphere/ cipro and ciprofloxacin-HCl-soaked Acuvue lenses (Acuvue; Johnson & Johnson Vision Care, Inc., Jacksonville, FL). RESULTS. Less than 2 g/mL of nanosphere/cipro effectively inhibited the proliferation of cultures inoculated with 10 7 or 10 8 bacteria/mL of S. aureus and P. aeruginosa, respectively. HEMA-based contact lenses polymerized with nanosphere/ cipro were transparent, effectively inhibited the proliferation of greater than 10 7 /mL of bacteria added daily over 3 days of culture, and killed up to 5 ϫ 10 9 total microbes in a single inoculation. A thicker lens design provided additional inhibition of bacterial growth for up to 96 hours. CONCLUSIONS. Core-shell nanospheres loaded with an antibiotic can be incorporated into a conventional, transparent contact lens and provide for sustained and effective bactericidal activity and thereby provide a new drug delivery platform for widespread use in treating ocular disorders. (Invest Ophthal