Aljinat/Kitosan Nanopartiküllere Pemetrekset Adsorpsiyonu ve Kontrollü İlaç Salımı

Yıl 2021, , 1066 - 1076, 18.12.2021

Ayça Erek , Safiye Kübra Aktaş , Yağmur Özdemir , Güliz Ak

https://doi.org/10.18185/erzifbed.1000206

Öz

Pemetrekset (PEM) küçük hücre dışı akciğer kanseri tedavisi için kullanılmaktadır. Bununla birlikte, pemetreksetin hızlı eliminasyon, düşük biyoyararlanım, zayıf tümör hücresi seçiciliği ve penetrasyon gibi sorunları vardır. Pemetreksetin akciğer kanseri hücrelerinde etkisini artırmak ve yan etkilerini en aza indirmek için ilaç taşıyıcı sistem kullanımına ihtiyaç vardır. Bu çalışmadaki amaç, biyobozunur ve non-toksik yapıdaki aljinat/kitosan nanopartiküllerine (ACNP) pemetrekset adsopsiyonunu gerçekleştirerek, pemetreksetin vücut içinde etkin bir şekilde taşınımını ve istenilen bölgede salımını sağlamaktır. Çalışmada iyonotropik jelasyon yöntemi kullanılarak aljinat/kitosan nanopartikülleri sentezlenip adsorpsiyon metodu ile pemetrekset taşıyıcı sisteme yüklendi. İlaç yükleme verimi % 57,80 olarak hesaplandı ve karakterizasyon testleri yapıldı. Pemetrekset yüklü aljinat/kitosan nanopartiküller (PACNP) ve serbest pemetrekset çözeltisi kullanılarak pH 5,5 ve 7,4 ortamlarında ilaç salım çalışmaları gerçekleştirildi. Elde edilen sonuçlar birbiriyle karşılaştırıldı. İlaç salım profili 25 saat boyunca izlendi ve nanopartiküllerden pH 7,4’te gözlenen %7’lik salım miktarının pH 5,5’ta %11’e yükseldiği belirlendi. Geliştirilen bu nanopartikül sistemi, pemetreksetin kontrollü salımı için daha ileri çalışmalarda in vitro ve in vivo olarak araştırılma potansiyeline sahiptir.

Anahtar Kelimeler

Aljinat/kitosan nanopartiküller, pemetrekset, adsorpsiyon, akciğer kanseri, pasif hedefleme

Alginate/Chitosan Nanoparticles for Adsorption and Controlled Release of Pemetrexed

Öz

Pemetrexed (PEM) is used for treatment of non-small cell lung cancer. However, PEM has disadvantages like fast elimination, low bioavailability, poor tumor cell selectivity, and penetration. Thus, there is a need for using pemetrexed delivery system to increase the anticancer effect of drug in lung cancer cells and to minimize its side effects. The purpose of this study is development of alginate/chitosan nanoparticles (ACNP) that have biodegradable and non-toxic structure for effective delivery of PEM for lung cancer therapy. In the present study, ACNP were prepared using the ionic gelation method, and pemetrexed was loaded via the adsorption method. Drug adsorption efficiency was calculated to be 57.80% and characterization studies were performed. In vitro drug release tests were carried out at pH levels of 5.5 and 7.4 with pemetrexed-loaded alginate/chitosan nanoparticles (PACNP) and free pemetrexed, and both the results were subsequently compared. Up to 11% release yield was observed at pH 5.5, and the yield reached up to 7% in pH 7.4 in the 25 hours. This nanoparticle system could be investigated in vitro and in vivo in further studies for controlled release of pemetrexed.

Anahtar Kelimeler

Alginate/chitosan nanoparticle, pemetrexed, adsorption, lung cancer, passive targeting

Kaynakça

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