AMFOTERİSİN-B ENKAPSÜLE EDİLMİŞ NANOPARTİKÜLLERİN ANTİMİKROBİYAL POTENSİNİN DEĞERLENDİRİLMESİ

Abstract

Amaç: Bu çalışmanın amacı, Amfoterisin B yüklü polimerik nanopartiküllerin geliştirilmesi ve Amfoterisin B nanoformülasyon örneklerinin ve ticari olarak temin edilen Amfoterisin B örneklerinin potensinin, Amerika Birleşik Devletleri Farmakopesi'nde ayrıntılı olarak açıklanan protokole göre referans Amfoterisin B standardı ile karşılaştırmalı olarak belirlenmesidir. Gereç ve Yöntem: Amfoterisin B nanopartikülleri tek emülsiyon yöntemi kullanılarak üretilmiştir. Referans Amfoterisin B standardının antimikrobiyal potensi ile ticari Amfoterisin B ve Amfoterisin B'nin nanoformülasyonunun potenslerinin kıyaslanması, Amerika Birleşik Devletleri Farmakopesinde belirtilen disk difüzyon yöntemi kullanılarak gerçekleştirilmiştir. Sonuç ve Tartışma: Ortalama hidrodinamik çapı 215.14±0.72 nm ve PDI değeri 0.18±0.02 olan Amfoterisin B yüklü poli(etilen glikol)-b-poli(ɛ-kaprolakton) nanopartikülleri başarıyla geliştirilmiştir. HPLC yöntemi kullanılarak belirlenen Amfoterisin B enkapsülasyon etkinliği %66.4±1.42 olarak bulunmuştur. Ticari Amfoterisin B'nin % potensi %95.7 olarak hesaplanırken, Amfoterisin B'nin nanoformülasyonunun % potensi %99.1 olarak hesaplanmış olup bu bulgu, taşıyıcı sistem olarak polimerik nanopartiküllerin kullanılmasının avantajını ortaya koymaktadır.

Keywords

• Amfoterisin B
• antimikrobiyal potens
• farmakope yöntemi
• polimerik nanopartiküller

DEVELOPMENT OF AMPHOTERICIN-B LOADED NANOPARTICLES AND EVALUATION THE ANTIMICROBIAL POTENCY

Abstract

Objective: The aim of this study is the development of Amphotericin B loaded polymeric nanoparticles and the determination of the potency of Amphotericin B nanoformulation samples and commercially supplied Amphotericin B samples in comparison with reference Amphotericin B standard, according to the protocol detailed in the United States Pharmacopoeia. Material and Method: Amphotericin B nanoparticles were fabricated using single emulsion method. The comparison of the potencies of the AmB nanoformulation and commercial Amphotericin B with the antimicrobial potency of the reference Amphotericin B standard was performed using the disk diffusion method specified in the United States Pharmacopeia. Result and Discussion: Amphotericin B loaded poly(ethylene glycol)-b-poly(ɛ-caprolactone) nanoparticles successfully developed having the average hydrodynamic diameter of 215.14±0.72 nm and PDI value of 0.18±0.02. The Amphotericin B encapsulation efficiency, which was determined using an HPLC method, was 66.4±1.42%. The % potency of commercial Amphotericin B was calculated as 95.7%, while the % potency of the nanoformulation of Amphotericin B was calculated as 99.1%, indicating the favor of utilizing polymeric nanoparticles as delivery systems.

Keywords

• Amphotericin B
• antimicrobial potency
• pharmacopoeia method
• polymeric nanoparticles

References

1. 1. Kocak, P., Oz U.C., Bolat, Z.B., Ozkose, U.U., Gulyuz, S., Tasdelen, M.A., Yılmaz, O., Bozkır, A., Sahin, F., Telci, D. (2021). The utilization of poly(2‐ethyl‐2‐oxazoline)‐b‐Poly(ε‐caprolactone) ellipsoidal particles for intracellular BIKDDA delivery to prostate cancer. Macromolecular Bioscience, 21(2), 2000287. [CrossRef]
2. 2. Oz, U.C., Bolat, Z.B., Poma, A., Guan, L., Telci, D., Sahin, F., Battaglia, G., Bozkır, A. (2020). Prostate cancer cell-specific BikDDA delivery by targeted polymersomes. Applied Nanoscience, 10(9), 3389-3401. [CrossRef]
3. 3. Lai, P., Daear, W., Löbenberg, R., Prenner, E.J. (2014). Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly(d,l-lactide-co-glycolic acid) and polyalkylcyanoacrylate. Colloids and Surfaces B: Biointerfaces, 118, 154-163. [CrossRef]
4. 4. Oz, U.C., Bolat, Z.B., Ozkose, U.U., Gulyuz, S., Kucukturkmen, B., Khalily, M.P., Ozcubukcu, S., Yılmaz, O., Telci, D., Esendaglı, G., Sahin, F., Bozkır, A. (2021). A robust optimization approach for the breast cancer targeted design of PEtOx-b-PLA polymersomes. Materials Science and Engineering: C, 123, 111929. [CrossRef]
5. 5. Oz, U.C., Devrim, B., Bozkır, A., Canefe, K. (2015). Development of reconstitutable suspensions containing diclofenac sodium-loaded microspheres for pediatric delivery. Journal of Microencapsulation, 32(4), 317-328. [CrossRef]
6. 6. Styliari, I.D., Taresco, V., Theophilus, A., Alexander, C., Garnet, M., Laughton, C. (2020). Nanoformulation-by-design: An experimental and molecular dynamics study for polymer coated drug nanoparticles. RSC Advances, 10(33), 19521-19533. [CrossRef]
7. 7. Anselmo, A.C., Mitragotri, S. (2019). Nanoparticles in the clinic: An update. Bioengineering & Translational Medicine, 4(3), e10143. [CrossRef]
8. 8. Ellis, D. (2002) Amphotericin B: Spectrum and resistance. Journal of Antimicrobial Chemotherapy, 49(suppl_1), 7-10. [CrossRef]

9. 9. Stone, N.R.H., Bicanic, T., Salim, R., Hope, W. (2016). Liposomal Amphotericin B (AmBisome®): A Review of the pharmacokinetics, pharmacodynamics, clinical experience and future directions. Drugs, 76(4), 485-500. [CrossRef]
10. 10. Dafale, N.A., Semwal, U.P., Rajput, R.K., Singh, G.N. (2016). Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance. Journal of Pharmaceutical Analysis, 6(4), 207-213. [CrossRef]
11. 11. Cengiz, G., Yapar, E.A., Kara, B.A., Sindhu, R.K. (2021). Comparison and evaluation of pharmacopoeial methods fort he assessment of potency of antibiotics. Universal Journal of Pharmaceutical Sciences, 6(3), 37-45.
12. 12. United States Pharmacopeia (2023). Rockville: The United States Pharmacopeia Convention, Chapter 81 Antibiotics-microbial assays.
13. 13. Dou, S., Yang, X.Z., Xiong M.H., Sun, C.Y., Yao, Y.D., Zhu, Y.H., Wang, J. (2014). ScFv-Decorated PEG-PLA-based nanoparticles for enhanced siRNA delivery to Her2 + breast cancer. Advanced Healthcare Materials, 3(11), 1792-1803. [CrossRef]
14. 14. Tiyaboonchai, W., Limpeanchob, N. (2007). Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles. International Journal of Pharmaceutics, 329(1-2), 142-149. [CrossRef]
15. 15. G. Nava-Arzaluz, M., Pinon-Sgundo, E., Ganem-Rondero, A., Lechuga-Ballesteros, D. (2012). Single Emulsion-Solvent Evaporation Technique and modifications for the preparation of pharmaceutical polymeric nanoparticles. Recent Patents on Drug Delivery & Formulation, 6(3), 209-223. [CrossRef]
16. 16. Sharma, N., Jandaik, S., Kumar, S. (2016). Synergistic activity of doped zinc oxide nanoparticles with antibiotics: Ciprofloxacin, ampicillin, fluconazole and amphotericin B against pathogenic microorganisms. Anais da Academia Brasileira de Ciências, 88(3), 1689-1698. [CrossRef]