Beyine İlaç Hedeflendirme Stratejileri

Year 2013, Issue: 2, 231 - 250, 01.06.2013

Selin S. Doğan Seçil Çaban Yılmaz Çapan

Abstract

Santral Sinir Sistemi SSS bozukluklarında kullanılmak üzere yeni ilaç molekülleri ve tedavilerin geliştirilmesi, beyin mikrodamarlarında bulunan sıkı kavşakların oluşturduğu Kan-Beyin Engeli KBE tarafından kısıtlanmaktadır. KBE, beyni toksik ve zararlı bileşiklerden korurken aynı zamanda çok sayıda ilaç molekülü için de engel teşkil etmektedir. Bu sebeple şizofreni, depresyon ve insomniayı kapsayan küçük bir grup dışındaki SSS hastalıkları KBE sebebiyle tedavi edilememektedir. SSS için ilaç geliştirilmesinde geri kalınmasının nedeni, yeni ilaç keşfi ve hedeflendirmenin iki ayrı disiplin olarak düşünülmesidir. Diğer alanlarda olduğu gibi gelişmenin yakalanabilmesi için temel yaklaşım, yeni ilaç molekülü ve hedeflendirme araştırmalarının beraber yürütülmesidir. Beyne ilaç hedeflendirme stratejileri, kimyasal ve biyoloji temelli disiplinlere dayanan iki gruba ayrılabilir. Geçmiş yıllarda, KBE’ye ilaç hedeflendirmede yapılan çalışmalar kimyasal yaklaşımlar alanında yoğunlaşmaktadır. Ancak günümüzde, biyolojik stratejilere dayanan, beyin kapiller endotel hücrelerindeki spesifik reseptörlere hedeflendirilmiş nanopartiküler sistemlerle umut verici çalışmalar yürütülmektedir. Bu derlemenin amacı, yeni stratejileri daha iyi anlayabilmek için, yürütülmüş önceki çalışmaların izlenmesine ek olarak yeni sistemlerin temellerinin incelenmesidir.

Keywords

İlaç hedeflendirme, kan-beyin engeli, reseptör aracılı transport

Brain Drug Targeting

Abstract

The development of new drug candidates and cures for Central Nervous System CNS disorders is restricted owing to the Blood-Brain Barrier BBB formed by the endothelial tight junctions within the brain microvasculature. The BBB protects brain from toxic and harmful compounds, but it also represents an obstacle for a large number of drugs. Thus, there are number of Central Nervous System CNS diseases that cannot be treated owing to the BBB problem, except the small group of CNS disorders including schizophrenia, depression and insomnia. The lag in CNS drug development is due to the fact that drug discovering and drug targeting are conducted as two separate disciplines. The major point to catch up with the progress in any other developing area is to carry on the researches for new drug development and targeting together. The brain drug targeting strategies can be divided into two groups derived from either chemistry based or biology-based disciplines. For the past decades, there has been a research interest in the area of chemical approaches for BBB targeting. But nowadays, promising applications of brain drug targeting have been done based on biologic strategies by nanoparticulate systems targeting specific receptors expressed in brain capillary endothelial cells. Therefore, the aim of this present review is to follow the time line of previous approaches to access to the CNS for better understanding of the new strategies as well as the basis of novel targeting systems.

Keywords

Drug targeting, blood-brain barrier, receptor mediated transport

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