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Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid

The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the...

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Autores principales: Bakhrushina, Elena O., Dubova, Anastasia I., Nikonenko, Maria S., Grikh, Viktoriya V., Shumkova, Marina M., Korochkina, Tatyana V., Krasnyuk, Ivan I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530203/
https://www.ncbi.nlm.nih.gov/pubmed/37754374
http://dx.doi.org/10.3390/gels9090693
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author Bakhrushina, Elena O.
Dubova, Anastasia I.
Nikonenko, Maria S.
Grikh, Viktoriya V.
Shumkova, Marina M.
Korochkina, Tatyana V.
Krasnyuk, Ivan I.
Krasnyuk, Ivan I.
author_facet Bakhrushina, Elena O.
Dubova, Anastasia I.
Nikonenko, Maria S.
Grikh, Viktoriya V.
Shumkova, Marina M.
Korochkina, Tatyana V.
Krasnyuk, Ivan I.
Krasnyuk, Ivan I.
author_sort Bakhrushina, Elena O.
collection PubMed
description The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor(®) P407, Kolliphor(®) P188, and PrincipHYAL(®) hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor(®) P407 poloxamer, 3% (w/v) Kolliphor(®) P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400–1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied.
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spelling pubmed-105302032023-09-28 Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid Bakhrushina, Elena O. Dubova, Anastasia I. Nikonenko, Maria S. Grikh, Viktoriya V. Shumkova, Marina M. Korochkina, Tatyana V. Krasnyuk, Ivan I. Krasnyuk, Ivan I. Gels Article The main method of treatment and prevention of endophthalmitis is a combination of intravitreal and topical administration of antibiotics, such as cefuroxime moxifloxacin or vancomycin. However, this method is ineffective due to the rapid elimination of the drug. This problem can be solved with the help of intravitreal in situ injection systems, which are injected with a syringe into the vitreous body and provide prolonged action of the drug at the focus of inflammation. Under the influence of temperature, the liquid drug undergoes a phase transition and turns into a gel after injection. This ensures its prolonged action. The study aimed to develop an intravitreal in situ cefuroxime delivery system for the treatment of endophthalmitis based on a thermosensitive biodegradable composition of poloxamer 407 and hyaluronic acid. A combination of poloxamer Kolliphor(®) P407, Kolliphor(®) P188, and PrincipHYAL(®) hyaluronic acids of different molecular weights was used as a delivery system. The potency of cefuroxime solid dispersion with polyvinylpyrrolidone-10000, polyethylene glycol-400, and polyethylene glycol-1500 in a 1:2 ratio was studied for prolonged action compared to cefuroxime substance. The experimental formulations were studied for the parameters of gelation temperature in a long-term test (4 months), pH, and release of cefuroxime using dialysis bags. To study the distribution parameter in the vitreous body, an in vitro model (1/13) was developed, which was a hollow agar sphere filled with 1% (w/v) polyacrylate gel. For the superior formulations, a HET-CAM test (chorioallantoic membrane test) was performed to determine the absence of irritant effects. According to the study results, a formulation containing a solid dispersion of cefuroxime:PEG-400 (1:2), the matrix of which contained 18% (w/v) Kolliphor(®) P407 poloxamer, 3% (w/v) Kolliphor(®) P188 poloxamer, and 0.5% (w/v) hyaluronic acid (1400–1800), was selected. This sample had an average gelation temperature of 34.6 °C, pH 6.7 ± 0.5, and a pronounced prolonged effect. Only 7.6% was released in 3 h of the experiment, whereas about 38% of cefuroxime was released in 72 h. No irritant effect on the chorioallantoic membrane was observed for any formulations studied. MDPI 2023-08-28 /pmc/articles/PMC10530203/ /pubmed/37754374 http://dx.doi.org/10.3390/gels9090693 Text en © 2023 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
Bakhrushina, Elena O.
Dubova, Anastasia I.
Nikonenko, Maria S.
Grikh, Viktoriya V.
Shumkova, Marina M.
Korochkina, Tatyana V.
Krasnyuk, Ivan I.
Krasnyuk, Ivan I.
Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title_full Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title_fullStr Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title_full_unstemmed Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title_short Thermosensitive Intravitreal In Situ Implant of Cefuroxime Based on Poloxamer 407 and Hyaluronic Acid
title_sort thermosensitive intravitreal in situ implant of cefuroxime based on poloxamer 407 and hyaluronic acid
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10530203/
https://www.ncbi.nlm.nih.gov/pubmed/37754374
http://dx.doi.org/10.3390/gels9090693
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