Naftokinon türevi bileşiklerin sol-jel metodu ile enkapsülasyonu ve karakterizasyonu
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Alkanna tinctoria'dan elde edilen doğal bir bileşik olan Alkannin, sahip olduğu naftazarin
iskelesi sayesinde antikanser aktivite gösterirmektedir. Bu çalışmada daha önce izole edilmiş ve saflaştırılmış β, β-dimetilakril alkannin bileşiğinin biyoyararlanımını arttırmak amacıyla, 0.25 M TEOS hidrolizatının prekürsör olarak kullanıldığı sol-jel tekniği ile silika-PAMAM dendrimer nanopartiküller içerisine enkapsüle edilmiştir. Sentez reaksiyonu için öncelikle, farklı konsantrasyonlarda ve pH değerlerindeki tamponlar (sodyum fosfat tamponu-PB ve fosfat tamponlu salin-PBS) optimize edilmiş ve daha sonra opimum koşullar kullanılarak, farklı karıştırma platformları (geleneksel kesikli üretim olan magnetik karıştırıcı ve karıştırmanın T-bağlantı mikrokanalında sürekli olduğu mikroakışkan platform) partikül boyut dağılımı açısından araştırılmıştır. Ayrıca sentezlenen nanopartiküller, Fourier Transform Infrared Spectroscopy, FTIR ile de karakterize edilmişlerdir. Geleneksel kesikli üretim denemeleri ile optimum konsantrasyonun 0.01 M PBS (pH 7.4) ve en düşük partikül boyutunun ise 182.9 ± 3.3 nm (± SEM) olduğu belirlenmiştir. Ancak sonuçlar, T-bağlantı mikrokarıştırıcı kullanılarak nanopartiküllerin ortalama büyüklüğünün 161.05 ± 1.45 nm'ye düşürülebileceğini ve geleneksel kesikli üretime kıyasla daha hızlı bir sentezin elde edilebileceğini göstermiştir. Ayrıca, β, β-dimetilakrylalkannin bileşiğinin sitotoksisitesi de, 3D hidrojel kullanılarak insan karaciğer karsinoması HepG2 hücrelerine karşı doza bağımlı bir şekilde incelenmiştir. PrestoBlue testi ile gerçekleştirilen sitotoksisite çalışmaları sonucunda, 3.125 μg / ml konsantrasyonda β, β-dimetilatrakrianannannin, 3. ve 7. günlerde en düşük hücre canlılığını sergilemiştir. Sentezlenmiş silika-PAMAM dendrimer hibrid nanopartiküller, invazif olmayan ilaç uygulamaları için partikül sentezi araştırmalarının ilerlemesine öncülük edebilecektir. Ayrıca, mikroakışkan sistemler; yüksek yeniden üretilebilirlik, kontrol edilebilirlik ve büyük ölçekli ilaç yüklü nanopartikül üretimleri için oldukça güçlü platformlardır.
Alkannin is a natural compound from Alkanna tinctoria and it exhibits anticancer activity through the naphthazarin scaffold. In this study, previously isolated and purified β,β- dimethylacryl alkannin was encapsulated in silica-PAMAM dendrimer with sol-gel technique using 0.25 M TEOS hydrolysate as a precursor. Firstly, different buffer types (sodium phosphate buffer and phosphate buffered saline) at different concentrations and pH values were optimized and then different mixing platforms (traditional batch production, and microfluidic platform where mixing is in T-junction microchannel continuously) were investigated in terms of particle size distribution which was determined using dynamic light scattering by Malvern Zetasizer Nano-ZS (Malvern Inst. Ltd., UK) and also synthesized nanoparticles were characterized by Fourier Transform Infrared Spectroscopy, FTIR. The optimum concentrations of compounds were 0.01 M PBS (pH 7.4) through traditional batch experiments yielding the lowest particle size of 182.9±3.3 nm (±SEM). On the other hand, the mean size of nanoparticles was decreased to 161.05±1.45 nm using T-junction micromixer and a more rapid synthesis was achieved in comparison to the traditional batch synthesis. Additionally, cytotoxicity of β,β-dimethylacrylalkannin against human liver carcinoma, HepG2 cells, was studied at a dose-dependent manner using 3D hydrogel. The PrestoBlue assay indicated that 3.125 μg/ml concentration β,β-dimethylacrylalkannin exhibited the lowest cell viabilities at day 3 and 7. The synthesized silica-PAMAM dendrimer hybrid nanoparticles might provide further routes to the particle formation research in the field of noninvasive drug delivery systems. Moreover, microfluidic systems are powerful platforms to synthesize nanoparticles with high reproducibility, controllability and suitable for large-scale production of drug-loaded nanoparticles.
Alkannin is a natural compound from Alkanna tinctoria and it exhibits anticancer activity through the naphthazarin scaffold. In this study, previously isolated and purified β,β- dimethylacryl alkannin was encapsulated in silica-PAMAM dendrimer with sol-gel technique using 0.25 M TEOS hydrolysate as a precursor. Firstly, different buffer types (sodium phosphate buffer and phosphate buffered saline) at different concentrations and pH values were optimized and then different mixing platforms (traditional batch production, and microfluidic platform where mixing is in T-junction microchannel continuously) were investigated in terms of particle size distribution which was determined using dynamic light scattering by Malvern Zetasizer Nano-ZS (Malvern Inst. Ltd., UK) and also synthesized nanoparticles were characterized by Fourier Transform Infrared Spectroscopy, FTIR. The optimum concentrations of compounds were 0.01 M PBS (pH 7.4) through traditional batch experiments yielding the lowest particle size of 182.9±3.3 nm (±SEM). On the other hand, the mean size of nanoparticles was decreased to 161.05±1.45 nm using T-junction micromixer and a more rapid synthesis was achieved in comparison to the traditional batch synthesis. Additionally, cytotoxicity of β,β-dimethylacrylalkannin against human liver carcinoma, HepG2 cells, was studied at a dose-dependent manner using 3D hydrogel. The PrestoBlue assay indicated that 3.125 μg/ml concentration β,β-dimethylacrylalkannin exhibited the lowest cell viabilities at day 3 and 7. The synthesized silica-PAMAM dendrimer hybrid nanoparticles might provide further routes to the particle formation research in the field of noninvasive drug delivery systems. Moreover, microfluidic systems are powerful platforms to synthesize nanoparticles with high reproducibility, controllability and suitable for large-scale production of drug-loaded nanoparticles.
Açıklama
Anahtar Kelimeler
Naftokinon, Nanopartikül, Sol-Jel, Naphthoquinone, Nanoparticles, Sol-Gel
