Berrin KÜÇÜKTÜRKMEN, Umut Can ÖZ, Asuman BOZKIR

PROTEİN VERİLİŞİ İÇİN KATI LİPİT MİKROPARTİKÜLLERİN HAZIRLANMASI VE İN VİTRO KARAKTERİZASYONU

Amaç: Bu araştırmanın amacı, katı lipid mikropartiküllerinin hazırlanması sırasında proses ve formülasyon parametrelerinin etkisini değerlendirmektir. Katı lipid mikropartiküller (SLM'ler), lipid nanopartiküllerinden daha az araştırılmış olmalarına rağmen biyouyumluluk, üretim ve karakterizasyon kolaylığı, uzun süreli salım ve özellikle yüksek protein yükleme kapasitesi gibi belirgin avantajlara sahiptir. Gereç ve Yöntem: SLM'ler, biyouyumlu ve biyolojik olarak parçalanabilen bir lipid olarak gliseril tridekanoat (GTD) kullanılarak emülsiyon çözücü difüzyon tekniği ile hazırlanmıştır. Homojen küresel mikropartiküller üretmek için en iyi formülasyon koşulları belirlenmiş ve bir üçgen faz diyagram alanı ile temsil edilmiştir. Mikropartiküller, formülasyon parametreleri değiştirilerek partikül boyutu ve enkapsülasyon etkinliği optimize edildikten sonra, seçilen formülasyonlar in vitro salım, morfolojik analizler, termal analiz ve elektroforetik analiz ile karakterize edilmiştir.Sonuç ve Tartışma: En yüksek etken madde yükleme etkinliği 100 mg lipid, %60 triasetin ve %3 emülgatör kullanılarak elde edilmiştir. Ortalama mikropartikül boyutu 8.9 µm olarak gözlenmiştir. İn vitro etken madde salımı pH 7.4 fosfat tampon çözeltisinde değerlendirilmiş ve 8. saatte tamamlanmıştır.

Anahtar Kelimeler:

Gliseril tridekanoat, Lipid mikropartikül, Sığır serum albümini, Triasetin, Üçgen faz diyagramı

PREPARATION AND IN VITRO CHARACTERIZATION OF SOLID LIPID MICROPARTICLES FOR PROTEIN DELIVERY

Objective: The aim of this research was to assess the effect of the process and formulation parameters during the preparation of solid lipid microparticles. Solid lipid microparticles (SLMs) have evident advantages such as biocompatibility, simplicity of production and characterization, prolonged release, and especially high protein loading capacity, despite being less investigated than lipid nanoparticles.Material and Method: SLMs were prepared via emulsion solvent diffusion technique using glyceryl tridecanoate (GTD) as a biocompatible and biodegradable lipid. The optimum formulation conditions for producing homogenous spherical microparticles were found and represented by a triangle phase diagram area. After optimizing the particle size and encapsulation efficiency by changing the formulation parameters, the microparticles were characterized by in vitro release, morphological analysis, thermal analysis and electrophoretic analysis on the selected formulations.Result and Discussion: The maximum drug loading efficiency was achieved by combining 100 mg of lipid, 60% triacetin and 3% emulsifier. The average microparticle size was observed as 8.9 μm. The in vitro drug release were analyzed in pH 7.4 phosphate buffer and were mainly completed at 8th hour.

Keywords:

Bovine serum albumin, glyceryl tridecanoate, lipid microparticle, triacetin, triangular phase diagram,

PDF

___

1. Din, F. U., Mustapha, O., Kim, D. W., Rashid, R., Park, J. H., Choi, J. Y., Ku, S.K., Yong, C.S., Kim, J.O., Choi, H. G. (2015). Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. European Journal of Pharmaceutics and Biophamaceutics, 94, 64-72. [CrossRef]
2. Trotta, M., Cavalli, R., Carlotti, M. E., Battaglia, L., Debernardi, F. (2005). Solid lipid micro-particles carrying insulin formed by solvent-in-water emulsion-diffusion technique. International Journal of Pharmacetics, 288(2), 281-288. [CrossRef]
3. Küçüktürkmen, B., Bozkır, A. (2018). Development and characterization of cationic solid lipid nanoparticles for co-delivery of pemetrexed and miR-21 antisense oligonucleotide to glioblastoma cells. Drug Development and Industrial Pharmacy, 44(2), 306-315. [CrossRef]
4. Scalia, S., Young, P. M., Traini, D. (2015). Solid lipid microparticles as an approach to drug delivery. Expert Opinion on Drug Delivery, 12(4), 583-599. [CrossRef]
5. Christophersen, P. C., Zhang, L., Müllertz, A., Nielsen, H. M., Yang, M., Mu, H. (2014). Solid lipid particles for oral delivery of peptide and protein drugs II--the digestion of trilaurin protects desmopressin from proteolytic degradation. Pharmaceutical Research, 31(9), 2420-2428. [CrossRef]
6. Bertoni, S., Tedesco, D., Bartolini, M., Prata, C., Passerini, N., Albertini, B. (2020). Solid Lipid Microparticles for Oral Delivery of Catalase: Focus on the Protein Structural Integrity and Gastric Protection. Molecular Pharmaceutics, 17(9), 3609-3621. [CrossRef]
7. Liu, J., Christophersen, P. C., Yang, M., Nielsen, H. M., Mu, H. (2017). The impact of particle preparation methods and polymorphic stability of lipid excipients on protein distribution in microparticles. Drug Development and Industrial Pharmacy, 43(12), 2032-2042. [CrossRef]
8. Saraf, S., Mishra, D., Asthana, A., Jain, R., Singh, S., Jain, N. K. (2006). Lipid microparticles for mucosal immunization against hepatitis B. Vaccine, 24(1), 45-56. [CrossRef]
9. Erni, C., Suard, C., Freitas, S., Dreher, D., Merkle, H. P., Walter, E. (2002). Evaluation of cationic solid lipid microparticles as synthetic carriers for the targeted delivery of macromolecules to phagocytic antigen-presenting cells. Biomaterials, 23(23), 4667-4676. [CrossRef]
10. Reithmeier, H., Herrmann, J., Göpferich, A. (2001). Lipid microparticles as a parenteral controlled release device for peptides. Journal of Controlled Release, 73(2-3), 339-350. [CrossRef]
11. Reithmeier, H., Herrmann, J., Göpferich, A. (2001). Development and characterization of lipid microparticles as a drug carrier for somatostatin. International Journal of Pharmaceutics, 218(1-2), 133-143. [CrossRef]
12. Choi, S. H., Jin, S. E., Lee, M. K., Lim, S. J., Park, J. S., Kim, B. G., Ahn, W.S., Kim, C. K. (2008). Novel cationic solid lipid nanoparticles enhanced p53 gene transfer to lung cancer cells. European Journal of Pharmaceutics and Biophamaceutics, 68(3), 545-554. [CrossRef]
13. Jin, S. E., Kim, C. K. (2012). Long-term stable cationic solid lipid nanoparticles for the enhanced intracellular delivery of SMAD3 antisense oligonucleotides in activated murine macrophages. Journal of Pharmacy and Pharmaceutical Sciences, 15(3), 467-482. [CrossRef]
14. Yuksel, N., Baykara, M., Shirinzade, H., Suzen, S. (2011). Investigation of triacetin effect on indomethacin release from poly(methyl methacrylate) microspheres: evaluation of interactions using FT-IR and NMR spectroscopies. International Journal of Pharmaceutics, 404(1-2), 102-109. [CrossRef]
15. Gharbavi, M., Manjili, H. K., Amani, J., Sharafi, A., Danafar, H. (2019). In vivo and in vitro biocompatibility study of novel microemulsion hybridized with bovine serum albumin as nanocarrier for drug delivery. Heliyon, 5(6), e01858. [CrossRef]
16. Rodriguez, L.B., Avalos, A., Chiaia, N., Nadarajah, A. (2017). Effect of Formulation and Process Parameters on Chitosan Microparticles Prepared by an Emulsion Crosslinking Technique. AAPS PharmSciTech.,18(4),1084-1094. [CrossRef]
17. Kraisit, P., Sarisuta, N. (2018). Development of Triamcinolone Acetonide-Loaded Nanostructured Lipid Carriers (NLCs) for Buccal Drug Delivery Using the Box-Behnken Design. Molecules, 23(4), 982. [CrossRef]
18. Sedyakina, N., Kuskov, A., Velonia, K., Feldman, N., Lutsenko, S., Avramenko, G. (2020). Modulation of Entrapment Efficiency and In Vitro Release Properties of BSA-Loaded Chitosan Microparticles Cross-Linked with Citric Acid as a Potential Protein-Drug Delivery System. Materials (Basel), 13(8), 1989. [CrossRef]
19. Beck, R.C., Pohlmann, A.R., Guterres, S.S. (2004). Nanoparticle-coated microparticles: preparation and characterization. Journal of Microencapsulation, 21(5), 499-512. [CrossRef] 20. Kim, D., Maharjan, P., Jin, M., Park, T., Maharjan, A., Amatya, R., Yang, J., Min, K.A., Shin, M. C. (2019). Potential Albumin-Based Antioxidant Nanoformulations for Ocular Protection against Oxidative Stress. Pharmaceutics, 11(7), 297. [CrossRef]