Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: <i>In Vitro</i> and <i>Ex Vivo</i> Evaluation

POLAT, Heybet Kerem; Kurt, Nihat; Aytekin, Eren; Akdag, Yagmur; Pehlivan, Sibel Bozdağ; Çalış, Sema

doi:10.1089/jop.2022.0008

Cited by 10 publications

(10 citation statements)

References 56 publications

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“…Thus, the milling process did not interfere with the in vitro antibiotic efficacy. Similar results were reported for different nano-based besifloxacin delivery: liposome [ 17 ], nanoemulsion [ 18 ], nanostructured lipid carrier [ 19 ], and nanofibrous [ 20 ] ( Table S2 ).…”

Section: Resultssupporting

confidence: 82%

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Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

et al. 2022

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Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in water, limiting its efficacy, a nanotechnology-based drug delivery preparation was developed to overcome this hurdle. Besifloxacin nanocrystals were prepared by small-scale wet milling and response surface methodology, using Povacoat® as a stabilizer. The particle’s average hydrodynamic diameter (Z-ave) was approximately 550 nm (17 times smaller than raw material), with a polydispersity index (PdI) of less than 0.2. The saturation solubility increased about two times compared to the raw material, making it possible to increase the dissolution rate of this drug substance, potentially improving its bioavailability and safety. The optimized preparation was stable under an accelerated stability study (90 days). The Z-ave, PZ, PdI, and content did not alter significantly during this period. Furthermore, the 0.6% m/m besifloxacin nanocrystals at the maximum dose and the Povacoat® stabilizer did not show toxicity in Galleria mellonella larvae. The innovative ophthalmic preparation minimum inhibitory concentration (MIC) was 0.0960 µg/mL and 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy. Therefore, besifloxacin nanocrystals revealed the potential for reduced dosing of the drug substance, with a minor occurrence of adverse effects and greater patient adherence to treatment.

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Section: Resultssupporting

confidence: 82%

“…Therefore, the retention time of drugs in the eye is minimal with consequently low bioavailability, generally less than 5% [ 16 , 17 ]. A different nano-based besifloxacin delivery was developed to overcome these challenges [ 17 , 18 , 19 , 20 ]. However, there are no besifloxacin nanocrystals reported in the literature.…”

Section: Introductionmentioning

confidence: 99%

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

et al. 2022

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“…NLT'de ilaç, farklı oranlarda katı ve sıvı lipidlere enkapsüle edilir. 37,38 NLT'ler, katı lipid nanopartiküllerin çekirdeklerindeki kristal yapısı ile ilgili kısıtlamaları çözmek için sıvı lipidlerinde eklendiği daha az kristalize yapılar elde etmek hedefiyle üretilmeye başlanmıştır. Bu iki formülasyonu birbirinden ayıran temel parametre çekirdek/matris içeriğidir.…”

Section: Nanopartikülunclassified

“…Bununla beraber NLT formülasyonlarının 6 saat süre ile yapılan ex vivo kornea geçiş çalışmasında piyasa preparatından daha iyi olduğu tespit edilmiştir (p<0,05). 37 Aytekin ve ark. ise yapmış oldukları bir çalışmada, keratokonus tedavisinde kullanılmak üzere riboflavin ve riboflavin-5-fosfat yüklü NLT formülasyonları hazırlamışlardır.…”

Section: Nanopartikülunclassified

Ocular Drug Delivery Systems: Traditional Review

POLAT¹,

Ünal²,

AYTEKİN³

et al. 2022

J Lit Pharm Sci

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“…Colloidal drug delivery is an advanced carrier system for increasing the therapeutic efficacy of the drug after ocular administration. There are various antibiotics-loaded nano-formulations for topical ophthalmic delivery that have been reported to improve therapeutic efficacy, such as besifloxacin-loaded liposome [ 6 ], CIP-loaded liposome [ 7 ], besifloxacin-loaded nanostructured lipid carrier [ 8 ], CIP- loaded nanoemulsion [ 9 ], vancomycin loaded niososme [ 10 ], and moxifloxacin loaded bilosomes [ 11 ]. Among them, bilosomes (BLO) are a novel and advanced carrier system for the enhancement of the ocular delivery of drugs.…”

Section: Introductionmentioning

confidence: 99%

Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study

Alsaidan

Zafar

Yasir

et al. 2022

Gels

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Conventional eye drops are most commonly employed topically in the eye for the management of bacterial conjunctivitis. Eye drops have a low corneal residence time and 90–95% of the administered dose is eliminated from the eye by blinking and the nasolacrimal drainage system. This problem can be minimized by formulating a mucoadhesive ocular in-situ gel system that undergoes sol-gel transition upon stimulation by temperature, pH, and ions. The goal of this study was to develop ciprofloxacin (CIP) loaded bilosomes (BLO) in-situ gel for the improvement of therapeutic efficacy. The BLO was prepared by the thin-film hydration method and optimized by the Box–Behnken design. Cholesterol (CHO), surfactant (Span 60), and bile salt (sodium deoxycholate/SDC) were used as formulation factors. The vesicle size (nm) and entrapment efficiency (%) were selected as responses (dependent factors). The optimized CIP-BLO (CIP-BLO-opt) formulation displayed a vesicle size of 182.4 ± 9.2 nm, a polydispersity index of 0.274, a zeta potential of −34,461.51 mV, and an entrapment efficiency of 90.14 ± 1.24%. Both x-ray diffraction and differential scanning calorimetry spectra did not exhibit extensive peaks of CIP in CIP-BLO-opt, revealing that CIP is encapsulated in the BLO matrix. The CIP-BLO-opt formulation was successfully incorporated into an in-situ gel system using a gelling agent, i.e., Carbopol 934P and hydroxyl propyl methyl cellulose (HPMC K100 M). CIP-BLO-opt in-situ gel formulation (CIP-BLO-opt-IG3) was evaluated for gelling capacity, clarity, pH, viscosity, in-vitro CIP release, bio-adhesive, ex-vivo permeation, toxicity, and antimicrobial study. The CIP-BLO-opt-IG3 exhibited satisfactory gelling properties with a viscosity of 145.85 ± 9.48 cP in the gelling state. CIP-BLO-opt-IG3 displayed sustained CIP release (83.87 ± 5.24%) with Korsmeyer–Peppas kinetic as a best-fitted model (R2 = 0.9667). CIP-BLO-opt-IG3 exhibited a 1.16-fold than CIP-IG and a 2.08-fold higher permeability than pure CIP. CIP-BLO-opt-IG3 displayed a significantly greater bio-adhesion property (924.52 ± 12.37 dyne/cm2) than tear film. Further, CIP-BLO-opt-IG3 does not display any toxicity as confirmed by corneal hydration (76.15%), histology, and the HET-CAM test (zero scores). CIP-BLO-opt-IG3 shows significantly higher (p < 0.05) antimicrobial activity against P. aeruginosa and S. aureus than pure CIP. From all these findings, it could be concluded that CIP-BLO-opt-IG3 might be an effective strategy for the increment of corneal residence time and therapeutic activity of CIP.

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Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: In Vitro and Ex Vivo Evaluation

Cited by 10 publications

References 56 publications

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

Ocular Drug Delivery Systems: Traditional Review

Development of Ciprofloxacin-Loaded Bilosomes In-Situ Gel for Ocular Delivery: Optimization, In-Vitro Characterization, Ex-Vivo Permeation, and Antimicrobial Study

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