Bakhrushina Elena O, Dubova Anastasia I, Nikonenko Maria S, Grikh Viktoriya V, Shumkova Marina M, Korochkina Tatyana V, Krasnyuk Ivan I, Krasnyuk Ivan I
Department of Pharmaceutical Technology, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia.
Student of Educational Department, A.P. Nelyubin Institute of Pharmacy, I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 119048, Russia.
Gels. 2023 Aug 28;9(9):693. doi: 10.3390/gels9090693.
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% (/) 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% (/) Kolliphor P407 poloxamer, 3% (/) Kolliphor P188 poloxamer, and 0.5% (/) 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.
眼内炎的主要治疗和预防方法是玻璃体内和局部应用抗生素联合使用，如头孢呋辛、莫西沙星或万古霉素。然而，由于药物快速消除，这种方法效果不佳。借助玻璃体内原位注射系统可以解决这个问题，该系统通过注射器注入玻璃体，并在炎症部位提供药物的长效作用。在温度影响下，液体药物发生相变，注射后变成凝胶。这确保了其长效作用。该研究旨在基于泊洛沙姆407和透明质酸的热敏性可生物降解组合物开发一种用于治疗眼内炎的玻璃体内原位头孢呋辛递送系统。使用不同分子量的泊洛沙姆科利凡P407、科利凡P188和普林西普透明质酸的组合作为递送系统。研究了头孢呋辛与聚乙烯吡咯烷酮-10000、聚乙二醇-400和聚乙二醇-1500以1:2比例的固体分散体与头孢呋辛原料药相比的长效作用。使用透析袋对实验制剂进行长期试验（4个月）中的凝胶化温度、pH值和头孢呋辛释放参数的研究。为了研究玻璃体中的分布参数，开发了一种体外模型（1/13），它是一个填充有1%（/）聚丙烯酸酯凝胶的中空琼脂球。对于性能优越的制剂，进行了鸡胚绒毛尿囊膜试验（HET-CAM试验）以确定是否存在刺激作用。根据研究结果，选择了一种含有头孢呋辛：聚乙二醇-400（1:2）固体分散体的制剂，其基质含有18%（/）泊洛沙姆科利凡P407、3%（/）泊洛沙姆科利凡P188和0.5%（/）透明质酸（1400 - 1800）。该样品的平均凝胶化温度为34.6℃，pH值为6.7±0.5，具有明显的长效作用。在实验的3小时内仅释放7.6%，而在72小时内约38%的头孢呋辛被释放。所研究的任何制剂对鸡胚绒毛尿囊膜均未观察到刺激作用。
