Publication: Synthesis and optimization of curcumin loaded levan-plga nanoparticles for targeted cancer therapy
Abstract
Kanser 21. yüzyılın en önemli sağlık sorunlarından biridir. NF-κB aktivasyonunun, transformasyon, radyo-direnç, metastaz, anjiyogenez, kemoresistans, invazyon, enflamasyon ve proliferasyon gibi çeşitli kanser ilişkili hücresel süreçlerle ilişkili olduğu bildirilmiştir. Zerdeçal baharatından elde edilen hidrofobik bir polifenol olan Kurkumin, NF-κB'nin aktivitesini baskılayabilme potansiyeline sahiptir ve bu da, tümörojenezde yer alan ve NF-κB tarafından regüle edilen birçok geninin baskılanmasını sağlar. Kurkuminin etkinliğine rağmen, hidrofobikliği ve düşük in vivo biyoyararlanımı nedeniyle klinikte kullanımı sınırlı kalmıştır.Nanopartikül bazlı ilaç taşıma sistemleri, düşük çözünürlük sergileyen terapötik ajanların taşınması için önemli potansiyellere sahiptir. PLGA biyomedikal uygulamalar için nanopartiküllerin tasarımında en sık kullanılan, FDA onaylı, biyobozunur ve biyouyumlu bir polimerdir. Levan ise, fruktoz halkaları arasında ß- (2-6) bağları olan β-D-fruktofuranozdan oluşan bir homopolisakkarittir. Bu biyouyumlu doğal polimerin amfifilik yapısı, ilaç taşıma uygulamalarındaki taşıyıcı rolünü kazandırmaktadır. Bu çalışma, kanser hücrelerinin üzerindeki şeker reseptörlerinin aşırı ekspresyonunu kullanarak, Kurkuminin terapötik potansiyelini ve aktif hedeflenmesini arttırmak için hidrofobik kurkuminin suda çözünürlüğünü, biyoyararlanımını, emilimini ve stabilitesini arttırmayı amaçlamıştır. Bu doğrultuda Kurkumin yüklü PLGA-Levan nanopartikülleri sentezlenmiş ve farklı yöntemlerle karakterize edilmiştir. Kurkumin yüklü nanopartiküllerin in vitro etkinliği, hücre ölümünün türü ve MCF-7 meme kanseri hücreleri tarafından nanopartiküllerin alınması ve formülasyonun NF-κB aktivasyonu üzerindeki etkisi araştırılmıştır.
Cancer is one of the major health concerns of the 21st century. NF-κB activation has been reported to be associated with miscellaneous cancer-related cellular processes such as transformation, radioresistance, metastasis, angiogenesis, chemoresistance, invasion, inflammation and proliferation. Curcumin, a hydrophobic polyphenol derived from the turmeric spice, has the potential to suppress the activity of NF-κB, resulting in a subsequent down-regulation of many NF-κB regulated genes which are involved in tumorogenesis. Despite the effectiveness of curcumin, its hydrophobicity and low in vivo bioavailability have limited its clinical usages. Nanoparticle-based drug delivery systems have noticeable potentials for delivery of therapeutic agents exhibiting poor aqueous solubility. PLGA is the most frequently used biodegradable and biocompatible polymer (approved by FDA) in designing nanoparticles for biomedical applications. Levan is a homopolysaccharide, formed by β-D-fructofuranose with ß-(2–6) linkages between fructose rings. This biocompatable natural polymer has amphiphilic structure by which levan gains the carrier role in drug delivery applications. The present study was an attempt to enhance aqueous solubility, bioavailability, absorption and stability of hydrophobic curcumin in order to increase its therapeutic potential and active targeting of cancer cells using overexpression of sugar receptors on these cells. Curcumin-loaded levan-PLGA nanoparticles were synthesized and characterized with different methods. In vitro efficiency of curcumin-loaded nanoparticles on viability, type of cell death and uptake of nanoparticles by MCF-7 cells and effect of formulation on NF-κB activation were investigated.
Cancer is one of the major health concerns of the 21st century. NF-κB activation has been reported to be associated with miscellaneous cancer-related cellular processes such as transformation, radioresistance, metastasis, angiogenesis, chemoresistance, invasion, inflammation and proliferation. Curcumin, a hydrophobic polyphenol derived from the turmeric spice, has the potential to suppress the activity of NF-κB, resulting in a subsequent down-regulation of many NF-κB regulated genes which are involved in tumorogenesis. Despite the effectiveness of curcumin, its hydrophobicity and low in vivo bioavailability have limited its clinical usages. Nanoparticle-based drug delivery systems have noticeable potentials for delivery of therapeutic agents exhibiting poor aqueous solubility. PLGA is the most frequently used biodegradable and biocompatible polymer (approved by FDA) in designing nanoparticles for biomedical applications. Levan is a homopolysaccharide, formed by β-D-fructofuranose with ß-(2–6) linkages between fructose rings. This biocompatable natural polymer has amphiphilic structure by which levan gains the carrier role in drug delivery applications. The present study was an attempt to enhance aqueous solubility, bioavailability, absorption and stability of hydrophobic curcumin in order to increase its therapeutic potential and active targeting of cancer cells using overexpression of sugar receptors on these cells. Curcumin-loaded levan-PLGA nanoparticles were synthesized and characterized with different methods. In vitro efficiency of curcumin-loaded nanoparticles on viability, type of cell death and uptake of nanoparticles by MCF-7 cells and effect of formulation on NF-κB activation were investigated.