Emine Dila KURTUL, Merve ÇAPKIN YURTSEVER

Genipin Çapraz Bağlı İnsan Serum Albumin Nanopartikülleri

İnsan serum albümin nanoparçacıkların (HSA-NP'ler), kontrollü ilaç salım çalışmalarında ilaç taşıyıcı sistemler olarak kullanımı günümüzde önem kazanmıştır. Albümin nanoparçacıkları, biyolojik olarak uyumludur, biyolojik olarak parçalanabilir ve sürekli salım sağlar. HSA nanoparçacıkların uzun süreli ilaç taşıyabilmesi için çapraz bağlanması gerekmektedir ve literatürde genellikle hücreler üzerinde toksik etkisi olan glutaraldehit ile çapraz baglama gerçekleştirilmektedir. Bu çalışmada, HSA nanoparçacıklarının desolvasyon tekniği ile başarılı bir şekilde üretilmesi için biyolojik bir kovalent çapraz bağlayıcı olan genipin kullanılmıştır. Çapraz bağlama süresini azaltmak için iki farklı sıcaklık ve genipin konsantrasyonu çalışılmıştır. Üretilen HSA nanoparçacıklarının karakterizasyonu, Taramalı Elektron Mikroskobisi (SEM) ve Dinamik Işık Saçılımı (DLS) yöntemleri ile gerçekleştirilmiştir. Sıcaklık oda sıcaklığından 37oC'ye yükseltilerek çapraz bağlanma süresi 8-24 saatten 2 saate düşürülmüştür. Genipin ile çapraz bağlanan HSA nanoparçacıkların, ilaç taşıyıcı sistemlerde ve kişiselleştirilmiş tıp uygulamalarında kullanımı potansiyel taşımaktadır.

Anahtar Kelimeler:

HSA, Genipin, Nanoparçacık, Desolvasyon

Genipin Crosslinked Human Serum Albumin Nanoparticles

The use of human serum albumin nanoparticles (HSA-NPs) as drug delivery systems in controlled drug release studies has gained importance today. Albumin nanoparticles are biocompatible, biodegradable and provide sustained release. To maintain long-term drug delivery, HSA nanoparticles need to be cross-linked. A chemical crosslinker, glutaraldehyde is generally used in the literature and has some toxic effects on the cells. In this study, a biological crosslinker, genipin, was used for the production of HSA nanoparticles by desolvation technique. Two different temperatures and genipin concentrations were studied in order to decrease crosslinking time. The nanoparticles were characterized by Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS). The crosslinking time was reduced from 8-24 hours to 2 hours by raising the temperature to 37oC from room temperature. HSA nanoparticles which are crosslinked by genipin may have potential use in drug delivery system and may be applied in personalized medicine applications.

Keywords:

HSA, Genipin, Nanoparticle, Desolvation,

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[1] A. Z. Wilczewska, K. Niemirowicz, K. H. Markiewicz, and H. Car, “Nanoparticles as drug delivery systems,” Pharmacological Reports, vol. 64, no. 5. Elsevier B.V., pp. 1020–1037, 2012. doi: 10.1016/S1734-1140(12)70901-5.
[2] J. K. Patra et al., “Nano based drug delivery systems: Recent developments and future prospects” Journal of Nanobiotechnology, vol. 16, no. 1. BioMed Central Ltd., Sep. 19, 2018. doi: 10.1186/s12951-018-0392-8.
[3] K. Langer, S. Balthasar, V. Vogel, N. Dinauer, H. von Briesen, and D. Schubert, “Optimization of the preparation process for human serum albumin (HSA) nanoparticles,” International Journal of Pharmaceutics, vol. 257, no. 1–2, pp. 169–180, May 2003, doi: 10.1016/S0378-5173(03)00134-0.
[4] R. Singh and J. W. Lillard, “Nanoparticle-based targeted drug delivery,” Experimental and Molecular Pathology, vol. 86, no. 3. pp. 215–223, Jun. 2009. doi: 10.1016/j.yexmp.2008.12.004.
[5] Y. G. Roh et al., “Protein Nanoparticle Fabrication for Optimized Reticuloendothelial System Evasion and Tumor Accumulation,” Langmuir, vol. 35, no. 11, pp. 3992–3998, Mar. 2019, doi: 10.1021/acs.langmuir.8b03776.
[6] S. Hong, D. W. Choi, H. N. Kim, C. G. Park, W. Lee, and H. H. Park, “Protein-based nanoparticles as drug delivery systems,” Pharmaceutics, vol. 12, no. 7. MDPI AG, pp. 1–28, Jul. 01, 2020. doi: 10.3390/pharmaceutics12070604.
[7] S. A. A. Rizvi and A. M. Saleh, “Applications of nanoparticle systems in drug delivery technology,” Saudi Pharmaceutical Journal, vol. 26, no. 1. Elsevier B.V., pp. 64–70, Jan. 01, 2018. doi: 10.1016/j.jsps.2017.10.012.
[8] F. Kratz, “A clinical update of using albumin as a drug vehicle - A commentary,” Journal of Controlled Release, vol. 190. Elsevier, pp. 331–336, Sep. 28, 2014. doi: 10.1016/j.jconrel.2014.03.013.
[9] F. Kratz, “Albumin as a drug carrier: Design of prodrugs, drug conjugates and nanoparticles,” Journal of Controlled Release, vol. 132, no. 3, pp. 171–183, Dec. 2008, doi: 10.1016/j.jconrel.2008.05.010.
[10] T. Pappa and S. Refetoff, “Thyroid hormone transport proteins: Thyroxine-binding globulin, transthyretin, and albumin,” in The Curated Reference Collection in Neuroscience and Biobehavioral Psychology, Elsevier Science Ltd., 2016, pp. 483–490. doi: 10.1016/B978-0-12-809324-5.03494-5.
[11] P. Lee and X. Wu, “Review: Modifications of Human Serum Albumin and Their Binding Effect,” 2015. doi: 10.2174/1381612821666150302115025.
[12] A. O. Elzoghby, W. M. Samy, and N. A. Elgindy, “Albumin-based nanoparticles as potential controlled release drug delivery systems,” Journal of Controlled Release, vol. 157, no. 2. pp. 168–182, Jan. 30, 2012. doi: 10.1016/j.jconrel.2011.07.031.
[13] M. Tarhini, H. Greige-Gerges, and A. Elaissari, “Protein-based nanoparticles: From preparation to encapsulation of active molecules,” International Journal of Pharmaceutics, vol. 522, no. 1–2. Elsevier B.V., pp. 172–197, Apr. 30, 2017. doi: 10.1016/j.ijpharm.2017.01.067.
[14] T. K. Giri, “Alginate Containing Nanoarchitectonics for Improved Cancer Therapy,” in Nanoarchitectonics for Smart Delivery and Drug Targeting, Elsevier Inc., 2016, pp. 565–588. doi: 10.1016/B978-0-323-47347-7.00020-3.
[15] S. Zhao, W. Wang, Y. Huang, Y. Fu, and Y. Cheng, “Paclitaxel loaded human serum albumin nanoparticles stabilized with intermolecular disulfide bonds,” Medchemcomm, vol. 5, no. 11, pp. 1658–1663, Nov. 2014, doi: 10.1039/c4md00200h.
[16] A. O. Elzoghby, M. M. Elgohary, and N. M. Kamel, “Implications of Protein- and Peptide-Based Nanoparticles as Potential Vehicles for Anticancer Drugs,” in Advances in Protein Chemistry and Structural Biology, vol. 98, Academic Press Inc., 2015, pp. 169–221. doi: 10.1016/bs.apcsb.2014.12.002.
[17] B. Manickam, R. Sreedharan, and M. Elumalai, “’Genipin’-The Natural Water Soluble Cross-linking Agent and Its Importance in the Modified Drug Delivery Systems: An Overview,” 2014. doi: 10.2174/15672018113106660059.
[18] J. Y. Lai, “Biocompatibility of genipin and glutaraldehyde cross-linked chitosan materials in the anterior chamber of the eye,” International Journal of Molecular Sciences, vol. 13, no. 9, pp. 10970–10985, Sep. 2012, doi: 10.3390/ijms130910970.
[19] G. Yang et al., “Assessment of the characteristics and biocompatibility of gelatin sponge scaffolds prepared by various crosslinking methods,” Scientific Reports, vol. 8, no. 1, Dec. 2018, doi: 10.1038/s41598-018-20006-y.
[20] N. Shahgholian, G. Rajabzadeh, and B. Malaekeh-Nikouei, “Preparation and evaluation of BSA-based hydrosol nanoparticles cross-linked with genipin for oral administration of poorly water-soluble curcumin,” International Journal of Biological Macromolecules, vol. 104, pp. 788–798, Nov. 2017, doi: 10.1016/j.ijbiomac.2017.06.083.
[21] R. Luo et al., “Genipin-crosslinked human serum albumin coating using a tannic acid layer for enhanced oral administration of curcumin in the treatment of ulcerative colitis,” Food Chemistry, vol. 330, Nov. 2020, doi: 10.1016/j.foodchem.2020.127241.
[22] J. Lin et al., “Genipin-crosslinked sugar beet pectin-bovine serum albumin nanoparticles as novel pickering stabilizer,” Food Hydrocolloids, vol. 112, Mar. 2021, doi: 10.1016/j.foodhyd.2020.106306.
[23] H. J. Lee et al., “Enzyme delivery using the 30Kc19 protein and human serum albumin nanoparticles,” Biomaterials, vol. 35, no. 5, pp. 1696–1704, Feb. 2014, doi: 10.1016/j.biomaterials.2013.11.001.
[24] M. Tarhini et al., “Human serum albumin nanoparticles as nanovector carriers for proteins: Application to the antibacterial proteins ‘neutrophil elastase’ and ‘secretory leukocyte protease inhibitor,’” International Journal of Pharmaceutics, vol. 579, Apr. 2020, doi: 10.1016/j.ijpharm.2020.119150.