ENTEROKOK ENFEKSİYONLARINDA KULLANILMAK ÜZERE VANCOMİSİN İÇEREN PLGA NANOPARTİKÜLLERİN HAZIRLANMASI VE KARAKTERİZASYONU

Yıl 2022, , 350 - 363, 29.05.2022

Gizem Rüya Topal , Merve Eylül Kıymacı , Yalçın Özkan

https://doi.org/10.33483/jfpau.1073081

Cited By: 4

Öz

Amaç: Bu çalışmada enterokok enfeksiyonlarında parenteral olarak kullanılabilecek Vankomisin yüklü poli(laktik asit-ko-glikolik asit) (PLGA) nanopartikülleri hazırlanması amaçlanmıştır.

Gereç ve Yöntem: Çalışmada, nanopartikülleri hazırlamak amacıyla farklı konsantrasyonlarda PLGA kullanılmıştır. Partiküllerin hazırlanmasında emülsiyon oluşturma-çözücü buharlaştırma yöntemi kullanılmıştır. Hazırlanan formülasyonların partikül büyüklüğü ve dağılımı, zeta potansiyeli, enkapsülasyon etkinliği, üretim verimi ölçülmüştür ve FTIR analizi yapılmıştır. Enterococcus faecalis ATCC 29212 suşu üzerine antibakteriyel aktivite sıvı mikrodilüsyon yöntemi ile minimum inhibisyon konsantrasyonu olarak ve disk difüzyon yöntemi ile inhibisyon zonu olarak Avrupa Antimikrobiyal Duyarlılık Testi Komitesi standartlarına göre belirlenmiş, sonuçlar saf etken madde ile karşılaştırılarak yorumlanmıştır.

Sonuç ve Tartışma: Partiküller emülsiyon-çözücü buharlaştırma yöntemi ile başarılı bir şekilde hazırlanmıştır. Yaklaşık 300 nm civarında; 0.26-0.28 PDI değerlerinde, enkapsüle olan Vankomisin miktarı oldukça yüksek partiküller elde edilmiştir. FTIR ve DSC analizi sonucu vankomisinin partikül içine yüklendiği tespit edilmiştir. Hazırlanan PLGA nanopartiküllerin Enterococcus faecalis ATCC 29212 suşu üzerine MİK değerleri 4 µg/ml bulunmuş, inhibisyon zon çapları ise sırasıyla 15 mm, 15 mm ve 16 mm olarak ölçülmüştür.

Anahtar Kelimeler

Antibakteriyel aktivite, Enterococcus faecalis, Nanopartikül, PLGA, Vankomisin

PREPARATION AND IN VITRO CHARACTERIZATION OF VANCOMYCIN LOADED PLGA NANOPARTICLES FOR THE TREATMENT OF ENTEROCOCCUS FAECALIS INFECTIONS

Öz

Objective: In this study, it was aimed to prepare Vancomycin loaded poly(lactic acid-co-glycolic acid) (PLGA) nanoparticles that can be used parenterally in enterococcal infections.

Material and Method: In the study, different concentrations of PLGA were used to prepare nanoparticles. Emulsification-solvent evaporation method was used in the preparation of the particles. Particle size and distribution, zeta potential, encapsulation efficiency and yield of the prepared formulations were determined. FTIR analyses were also performed for the formulations. The antibacterial activity was determined as a minimum inhibition concentration by broth microdilution method and as an inhibition zone by disk diffusion method against Enterococcus faecalis ATCC 29212 according to European Committee on Antimicrobial Susceptibility Testing and its effectiveness on bacteria was interpreted by comparing with the pure active substance.

Result and Discussion: Particles were successfully prepared by emulsion-solvent evaporation method. Around 300 nm; Particles with a high amount of encapsulated Vancomycin were obtained at PDI values of 0.26-0.28. As a result of the FTIR analysis, it was determined that Vancomycin was loaded into the particle. The MIC values of the prepared PLGA nanoparticles against Enterococcus faecalis ATCC 29212 strain was found to be 4 µg/ml, and the inhibition zone diameters were measured as 15 mm, 15 mm and 16 mm, respectively.

Anahtar Kelimeler

Antibacterial activity, Enterococcus faecalis, Nanoparticles, PLGA, Vancomycin

Kaynakça

• Yıldırım, M. (2022). Enterokoklar ve Enterokoklarla Gelisen Infeksiyonlar. 9.
• Said MS, Tirthani E, Lesho E. Enterococcus Infections. (2021). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021
• Tünger, Ö. (2012). Vankomisine dirençli enterokok infeksiyonlarının tedavisinde eski ve yeni tedavi seçenekleri. ANKEM Dergisi, 26(4), 215-227.
• Soppimath, K. S., Aminabhavi, T. M., Kulkarni, A. R., & Rudzinski, W. E. (2001). Biodegradable polymeric nanoparticles as drug delivery devices. Journal of Controlled Release, 70(1), 1-20.
• Anderson, J. M., & Shive, M. S. (1997). Biodegradation and biocompatibility of PLA and PLGA microspheres. Advanced Drug Delivery Reviews, 28(1), 5-24.
• Valizadeh, H., Mohammadi, G., R.Ehyaei, Milani, M., Azhdarzadeh, M., Zakeri-Milani, P., & Lotfipour, F. (2012). Antibacterial activity of clarithromycin loaded PLGA nanoparticles. Pharmazie, 67, 63-68.
• Verderio, P., Bonetti, P., Colombo, M., Pandolfi, L., & Prosperi, D. (2013). Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2/M block in breast cancer cells. Biomacromolecules, 14(3), 672-682.
• Lotfipour, F., Abdollahi, S., Jelvehgari, M., Valizadeh, H., Hassan, M., & Milani, M. (2014). Study of antimicrobial effects of vancomycin loaded PLGA nanoparticles against enterococcus clinical isolates. Drug Res (Stuttg), 64(7), 348-352.
• Anwer, M. K., Al-Mansoor, M. A., Jamil, S., Al-Shdefat, R., Ansari, M. N., & Shakeel, F. (2016). Development and evaluation of PLGA polymer based nanoparticles of quercetin. Int J Biol Macromol, 92, 213-219.
• Esim, O., Bakirhan, N. K., Sarper, M., Savaser, A., Ozkan, S. A., & Ozkan, Y. (2020). Influence of emulsifiers on the formation and in vitro anticancer activity of epirubicin loaded PLGA nanoparticles. Journal of Drug Delivery Science and Technology, 60, 102027.
• Zakeri-Milani, P., Loveymi, B. D., Jelvehgari, M., & Valizadeh, H. (2013). The characteristics and improved intestinal permeability of vancomycin PLGA-nanoparticles as colloidal drug delivery system. Colloids Surf B Biointerfaces, 103, 174-181.
• Topal, G. R., Devrim, B., Eryilmaz, M., & Bozkir, A. (2018). Design of ciprofloxacin-loaded nano-and microcomposite particles for dry powder inhaler formulations: preparation, in vitro characterisation, and antimicrobial efficacy. J Microencapsul, 35(6), 533-547.
• Simon, A., Moreira, M. L. A., Costa, I., de Sousa, V. P., Rodrigues, C. R., da Rocha, E. L. L. M. T., . . . Cabral, L. M. (2020). Vancomycin-loaded nanoparticles against vancomycin intermediate and methicillin resistant Staphylococcus aureus strains. Nanotechnology, 31(37), 375101.
• EUCAST Web site. (2021). European Committee on Antimicrobial Susceptibility Testing. https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf Accessed date: 9.12.2021.
• Tewes, F., Munnier, E., Antoon, B., Ngaboni Okassa, L., Cohen-Jonathan, S., Marchais, H., . . . Chourpa, I. (2007). Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods. Eur J Pharm Biopharm, 66(3), 488-492.
• Sabaeifard, P., Abdi-Ali, A., Soudi, M. R., Gamazo, C., & Irache, J. M. (2016). Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa. Eur J Pharm Sci, 93, 392-398.
• Seju, U., Kumar, A., & Sawant, K. K. (2011). Development and evaluation of olanzapine-loaded PLGA nanoparticles for nose-to-brain delivery: In vitro and in vivo studies. Acta Biomaterialia, 7(12), 4169-4176.
• Quintanar-Guerrero, D., Fessi, H., Allémann, E., & Doelker, E. (1996). Influence of stabilizing agents and preparative variables on the formation of poly(d,l-lactic acid) nanoparticles by an emulsification-diffusion technique. International Journal of Pharmaceutics, 143(2), 133-141.
• Mainardes, R. M., & Evangelista, R. C. (2005). PLGA nanoparticles containing praziquantel: effect of formulation variables on size distribution. International Journal of Pharmaceutics, 290(1), 137-144.
• Bacanlı, M., Eşi̇m, Ö., Erdoğan, H., Sarper, M., Erdem, O., & Özkan, Y. (2021). Evaluation of cytotoxic and genotoxic effects of paclitaxel-loaded PLGA nanoparticles in neuroblastoma cells. Food and Chemical Toxicology, 154, 112323.
• Tefas, L. R., Tomuţă, I., Achim, M., & Vlase, L. (2015). Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design. Clujul medical (1957), 88(2), 214-223.
• Elsewedy, H. S., Dhubiab, B. E. A., Mahdy, M. A., & Elnahas, H. M. (2020). Development, optimization, and evaluation of PEGylated brucine-loaded PLGA nanoparticles. Drug Delivery, 27(1), 1134-1146.
• Murakami, H., Kobayashi, M., Takeuchi, H., & Kawashima, Y. (1999). Preparation of poly(DL-lactide-co-glycolide) nanoparticles by modified spontaneous emulsification solvent diffusion method. Int J Pharm, 187(2), 143-152.
• Singh, G., Tanurajvir, K., Ravinder, K., & Kaur, A. (2014). Recent biomedical applications and patents on biodegradable polymer-PLGA. International Journal of Pharmacology and Pharmaceutical Sciences, 1, 30-42.
• Sunanda Laxmi, P., Vidyavathi, M., & Venkata, S. K. R. (2021). DoE approach for development of localized controlled release microspheres of Vancomycin for treatment of septic arthritis. Future Journal of Pharmaceutical Sciences, 7(1).
• Alonso, M. J., Losa, C., Calvo, P., & Vila-Jato, J. (1991). Approaches to improve the association of amikacin sulphate to poly(alkylcyanoacrylate) nanoparticles. International Journal of Pharmaceutics, 68(1), 69-76.
• Abeylath, S. C., Turos, E., Dickey, S., & Lim, D. V. (2008). Glyconanobiotics: Novel carbohydrated nanoparticle antibiotics for MRSA and Bacillus anthracis. Bioorg Med Chem, 16(5), 2412-2418.