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Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation

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...

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Autores principales: de Jesus, José Izo Santana da Silva, Lourenço, Felipe Rebello, Ishida, Kelly, Barreto, Thayná Lopes, Avino, Valdir Carlos, Neto, Edson dos Santos, Bou-Chacra, Nádia Araci
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609799/
https://www.ncbi.nlm.nih.gov/pubmed/36297656
http://dx.doi.org/10.3390/pharmaceutics14102221
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author de Jesus, José Izo Santana da Silva
Lourenço, Felipe Rebello
Ishida, Kelly
Barreto, Thayná Lopes
Avino, Valdir Carlos
Neto, Edson dos Santos
Bou-Chacra, Nádia Araci
author_facet de Jesus, José Izo Santana da Silva
Lourenço, Felipe Rebello
Ishida, Kelly
Barreto, Thayná Lopes
Avino, Valdir Carlos
Neto, Edson dos Santos
Bou-Chacra, Nádia Araci
author_sort de Jesus, José Izo Santana da Silva
collection PubMed
description 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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spelling pubmed-96097992022-10-28 Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation de Jesus, José Izo Santana da Silva Lourenço, Felipe Rebello Ishida, Kelly Barreto, Thayná Lopes Avino, Valdir Carlos Neto, Edson dos Santos Bou-Chacra, Nádia Araci Pharmaceutics Article 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. MDPI 2022-10-18 /pmc/articles/PMC9609799/ /pubmed/36297656 http://dx.doi.org/10.3390/pharmaceutics14102221 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
de Jesus, José Izo Santana da Silva
Lourenço, Felipe Rebello
Ishida, Kelly
Barreto, Thayná Lopes
Avino, Valdir Carlos
Neto, Edson dos Santos
Bou-Chacra, Nádia Araci
Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title_full Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title_fullStr Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title_full_unstemmed Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title_short Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
title_sort besifloxacin nanocrystal: towards an innovative ophthalmic preparation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609799/
https://www.ncbi.nlm.nih.gov/pubmed/36297656
http://dx.doi.org/10.3390/pharmaceutics14102221
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