KATI LİPİT NANOPARTİKÜLLER VE BEYNE ÖZGÜ İLAÇ TAŞIYICI SİSTEM OLARAK UYGULAMALARI

Year 2021, , 428 - 442, 31.05.2021

Mahmut Ozan Toksoy , Fahriye Figen Tırnaksız

https://doi.org/10.33483/jfpau.855788

Abstract

Amaç: Son 20 yılda nanoteknolojik gelişmeler ile birlikte ilaç moleküllerinin beyne hedeflenmesine yönelik çalışmalarda artış gözlenmektedir. Beyin, kan dolaşımından kendine özgü bir bariyer ile ayrılmıştır. Kan-beyin bariyeri olarak adlandırılan bu yapı astrosit, perisit, endotel hücreleri ve bunlar arasında bulunan sıkı bağlantılardan oluşmaktadır. Moleküllerin beyne geçişini engelleyen enzimatik aktivitenin yanında, beynin sistemik dolaşımdan kan-beyin bariyeri ile ayrılması, terapötik moleküllerinin beyne geçişini olumsuz etkilemektedir. Bu yüzden merkezi sinir sistemi rahatsızlıklarında tedavi zorlaşmakta, terapötik etki azalmakta veya gözlenememektedir. Bu durumu anlamak ve olası sorunları giderebilmek için beynin ve kan-beyin bariyerinin yapısı bilinmeli, ilaç moleküllerinin geçiş mekanizmaları aydınlatılmalıdır. Beyne hedeflemede ilaç taşıyıcı sistemlerin önemi günden güne artmaktadır. Üretilen sistemler arasında katı lipit nanopartiküllerin kolay üretimi, biyo-uyumluluğu, biyo-bozunabilirliği açısından diğer sistemlere göre avantajları bulunmaktadır. Bu derlemede, kan beyin bariyerinden bahsedilmesi, beyne ilaç hedefleme yöntemlerinin açıklanması ve beyne ilaç moleküllerinin hedeflenmesinde katı lipit nanopartiküllerle yapılan çalışmalardan söz edilmesi amaçlanmıştır.

Sonuç ve Tartışma: İlaç moleküllerinin beyne hedeflenmesinde kan-beyin bariyeri en büyük engeldir. Bu engeli aşabilmek amacıyla geliştirilen sistemlerden biri de katı lipit nanopartiküller olmuş, sayısız çalışmalarla etkinliği kanıtlanmıştır. Hedefleme ile merkezi sinir sistemi rahatsızlıklarında ilaçların etkinliğinin arttırılabileceği görülmüştür.

Keywords

Beyne hedefleme, İlaç taşıyıcı sistemler, Kan-beyin bariyeri, Katı lipit nanopartiküller

SOLID LIPID NANOPARTICLES AND APPLICATIONS AS BRAIN SPECIFIC DRUG DELIVERY SYSTEMS

Abstract

Objective: In the last 20 years, with the nanotechnological developments, there has been an increase in studies aimed at targeting drug molecules to the brain. The brain is separated from bloodstream by a unique barrier. This structure, called the blood-brain barrier, which consists of astrocytes, pericytes, endothelial cells and tight junctions between them. Apart from the enzymatic activity that prevents the passage of molecules to the brain, the separation of the brain from the systemic blood circulation by the blood-brain barrier negatively affects the passage of therapeutic molecules. The structure of the brain and the blood-brain barrier must be known and the penetration mechanisms of drug molecules to the brain must be elucidated. In this review, we aimed to mention the blood-brain barrier and drug targeting methods to the brain. Also, importance of the solid lipid nanoparticles in targeting drug molecules to the brain will be emphasized.

Result and Discussion: Blood-brain barrier is the biggest obstacle in targeting drug molecules to the brain. One of the systems developed to overcome this obstacle is solid lipid nanoparticles. It has been observed that the effectiveness of drugs in central nervous system disorders can be increased by targeting.

Keywords

Blood-brain barrier, Drug delivery systems, Solid lipid nanoparticles, Targeting to the brain

References

• Agrawal, M., Saraf, S., Saraf, S., Dubey, S. K., Puri, A., Patel, R. J., Alexander, A. (2020). Recent strategies and advances in the fabrication of nano lipid carriers and their application towards brain targeting. Journal of Controlled Release, 321, 372-415.
• Biopharma Dealmakers (2020). Erişim tarihi 30.12.2020, A view into the central nervous system disorders market, https://www.nature.com/articles/d43747-020-01119-8.
• Khan, A. R., Yang, X., Fu, M., and Zhai, G. (2018). Recent progress of drug nanoformulations targeting to brain. Journal of Controlled Release, 291, 37-64.
• Mehnert, W., and Mäder, K. (2012). Solid lipid nanoparticles: production, characterization and applications. Advanced Drug Delivery Reviews, 64, 83-101.
• Barnabas, W. (2019). Drug targeting strategies into the brain for treating neurological diseases. Journal of Neuroscience Methods, 311, 133-146.
• Blasi, P., Giovagnoli, S., Schoubben, A., Ricci, M., and Rossi, C. (2007). Solid lipid nanoparticles for targeted brain drug delivery. Advanced Drug Delivery Reviews, 59(6), 454-477.
• Maherally, Z., Fillmore, H. L., Tan, S. L., Tan, S. F., Jassam, S. A., Quack, F. I., Pilkington, G. J. (2018). Real-time acquisition of transendothelial electrical resistance in an all-human, in vitro, 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity. FASEB Journal, 32(1), 168-182.
• Ghersi-Egea, J. F., Leninger-Muller, B., Suleman, G., Siest, G., and Minn, A. (1994). Localization of drug-metabolizing enzyme activities to blood-brain interfaces and circumventricular organs. Journal of Neurochemistry, 62(3), 1089-1096.
• Pardridge, W. M. (2002). Drug and gene delivery to the brain: the vascular route. Neuron, 36(4), 555-558.
• KrolI, R. A., and Neuwelt, E. A. (1998). Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Journal of Neurosurgery, 42(5), 1083-1099.
• Choi, J. J., Feshitan, J. A., Baseri, B., Wang, S., Tung, Y. S., Borden, M. A., and Konofagou, E. E. (2009). Microbubble-size dependence of focused ultrasound-induced blood–brain barrier opening in mice in vivo. Transactions on Biomedical Engineering, 57(1), 145-154.
• Bodor, N., and Buchwald, P. (2003). Brain-targeted drug delivery. American Journal of Drug Delivery, 1(1), 13-26.
• Harbaugh, R. E., Saunders, R. L., and Reeder, R. F. (1988). Use of implantable pumps for central nervous system drug infusions to treat neurological disease. Journal of Neurosurgery, 23(6), 693-698.
• Chan, K. Y., Jang, M. J., Yoo, B. B., Greenbaum, A., Ravi, N., Wu, W. L., Gradinaru, V. (2017). Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems. Nature Neuroscience, 20(8), 1172-1179.
• Li, Y., Zhou, Y., Jiang, J., Wang, X., Fu, Y., Gong, T., Zhang, Z. (2015). Mechanism of brain targeting by dexibuprofen prodrugs modified with ethanolamine-related structures. Journal of Cerebral Blood Flow and Metabolism, 35(12), 1985-1994.
• Stalmans, S., Bracke, N., Wynendaele, E., Gevaert, B., Peremans, K., Burvenich, C., De Spiegeleer, B. (2015). Cell-Penetrating Peptides Selectively Cross the Blood-Brain Barrier In Vivo. PLOS One, 10(10), e0139652.
• Pardeshi, C. V., and Belgamwar, V. S. (2013). Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting. Expert Opinion on Drug Delivery, 10(7), 957-972.
• Gänger, S., and Schindowski, K. (2018). Tailoring formulations for intranasal nose-to-brain delivery: A review on architecture, physico-chemical characteristics and mucociliary clearance of the nasal olfactory mucosa. Journal of Pharmaceutics, 10(3), 116.
• Lewis, D. F., and Dickins, M. (2002). Substrate SARs in human P450s. Drug Discovery Today, 7(17), 918-925.
• Gao, H. (2016). Progress and perspectives on targeting nanoparticles for brain drug delivery. Acta Pharmaceutica Sinica B, 6(4), 268-286.
• Kaur, I. P., Bhandari, R., Bhandari, S., and Kakkar, V. (2008). Potential of solid lipid nanoparticles in brain targeting. Journal of Controlled Release, 127(2), 97-109.
• Gastaldi, L., Battaglia, L., Peira, E., Chirio, D., Muntoni, E., Solazzi, I., Dosio, F. (2014). Solid lipid nanoparticles as vehicles of drugs to the brain: current state of the art. European Journal of Pharmaceutics and Biopharmaceutics, 87(3), 433-444.
• Pooja, D., Tunki, L., Kulhari, H., Reddy, B. B., and Sistla, R. (2016). Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method. Data in Brief, 6, 15-19.
• Gallarate, M., Trotta, M., Battaglia, L., and Chirio, D. (2009). Preparation of solid lipid nanoparticles from W/O/W emulsions: preliminary studies on insulin encapsulation. Journal of Microencapsulation, 26(5), 394-402.
• Kaushik, M., Mohan, G., Shukla, T. P., Upadhyay, N., Mathur, A., and Cherian, B. (2012). Formulation development and evaluation of solid lipid nanoparticles of aceclofenac using solvent injection method. Journal of Drug Delivery and Therapeutics, 2(4).
• Silva, A. C., Gonzalez-Mira, E., Garcia, M. L., Egea, M. A., Fonseca, J., Silva, R., Ferreira, D. (2011). Preparation, characterization and biocompatibility studies on risperidone-loaded solid lipid nanoparticles (SLN): high pressure homogenization versus ultrasound. Colloids and Surfaces B Biointerfaces, 86(1), 158-165.
• Karami, M. A., Zadeh, B. S. M., Koochak, M., and Moghimipur, E. (2016). Superoxide dismutase-loaded solid lipid nanoparticles prepared by cold homogenization method: characterization and permeation study through burned rat skin. Jundishapur Journal of Natural Pharmaceutical Products, 11, e33968.
• Cavalli, R., Gasco, M. R., Chetoni, P., Burgalassi, S., and Saettone, M. F. (2002). Solid lipid nanoparticles (SLN) as ocular delivery system for tobramycin. International Journal of Pharmaceutics, 238(1-2), 241-245.
• Jose, S., Anju, S. S., Cinu, T. A., Aleykutty, N. A., Thomas, S., and Souto, E. B. (2014). In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery. International Journal of Pharmaceutics, 474(1-2), 6-13.
• Graverini, G., Piazzini, V., Landucci, E., Pantano, D., Nardiello, P., Casamenti, F., Bergonzi, M. C. (2018). Solid lipid nanoparticles for delivery of andrographolide across the blood-brain barrier: in vitro and in vivo evaluation. Colloids and Surfaces B Biointerfaces, 161, 302-313.
• Erel-Akbaba, G., Carvalho, L. A., Tian, T., Zinter, M., Akbaba, H., Obeid, P. J., Tannous, B. A. (2019). Radiation-Induced Targeted Nanoparticle-Based Gene Delivery for Brain Tumor Therapy. ACS Nano, 13(4), 4028-4040.
• Abou Youssef, N. A. H., Kassem, A. A., Farid, R. M., Ismail, F. A., Magda Abd Elsamea, E. M., and Boraie, N. A. (2018). A novel nasal almotriptan loaded solid lipid nanoparticles in mucoadhesive in situ gel formulation for brain targeting: preparation, characterization and in vivo evaluation. International Journal of Pharmaceutics, 548(1), 609-624.
• Singh, I., Swami, R., Pooja, D., Jeengar, M. K., Khan, W., and Sistla, R. (2016). Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting. Journal of Drug Targeting, 24(3), 212-223.
• Dal Magro, R., Ornaghi, F., Cambianica, I., Beretta, S., Re, F., Musicanti, C., Sancini, G. (2017). ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier. Journal of Controlled Release, 249, 103-110.
• Fatouh, A. M., Elshafeey, A. H., and Abdelbary, A. (2017). Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics. Drug Design, Development and Therapy, 11, 1815-1825.
• Hady, M. A., Sayed, O. M., and Akl, M. A. (2020). Brain uptake and accumulation of new levofloxacin-doxycycline combination through the use of solid lipid nanoparticles: Formulation; Optimization and in-vivo evaluation. Colloids Surfaces B: Biointerfaces, 111076.