AKCİĞER TÜMÖRLERİNE YÖNELİK PAKLİTAKSEL YÜKLÜ POLİKAPROLAKTON NANOPARTİKÜLLERİ; FORMÜLASYON, KAPSAMLI İN VİTRO KARAKTERİZASYON VE SALIM KİNETİK ÇALIŞMALARI

Öz

Amaç: Günümüzde kanser hala en sık görülen kronik hastalıklar arasında yer almaktadır. Polikaprolakton gibi biyouyumlu ve biyoparçalanır polimerlerle hazırlanan nanopartiküler ilaç taşıyıcı sistemler, düşük çözünürlük ve düşük biyoyararlanım gösteren birçok antikanser ajan için rasyonel bir çözümdür. Bu çalışmanın amacı, güçlü bir antikanser olduğu bilinen paklitaksel yüklü polikaprolakton nanopartiküllerinin hazırlanması ve hazırlanan nanopartiküllerin in vitro karakterizasyonlarını ve salım kinetik mekanizmalarını aydınlatmaktır.
Gereç ve Yöntem: Nanoçöktürme yöntemi ile paklitaksel yüklü polikaprolakton nanopartiküllerinin hazırlanması amaçlanmıştır. Polikaprolakton polimerinin iki farklı moleküler ağırlığı (Mw: 14.000 ve Mw: 80.000) ile ön formülasyon çalışmaları yapılmıştır. Hazırlanan nanopartiküller, katyonik yüzey yükü elde etmek ve hücresel etkileşimi artırmak için Chitosan (CS) veya Poly-l-lisin (PLL) ile ayrı ayrı kaplanmıştır. Formülasyonların kapsamlı karakterizasyon çalışmaları ve salım kinetik çalışmaları yapılmıştır.
Sonuç ve Tartışma: Formülasyonların partikül boyutu 188 nm ila 383 nm arasında değişmektedir. Enkapsülasyon etkinliği, farklı formülasyonlarda %77'ye kadar yükselmiştir. SEM analizi, nanopartiküllerin küre şeklinde olduğunu doğrulamıştır. İn vitro salım çalışmaları kapsamında 96 saate kadar salım devam etmiş ve ilk 24 saatte terapötik yükün %50'sinden azı salınmıştır. Matematiksel modelleme çalışmaları, formülasyonların salım kinetiğinin, yüksek korelasyon gösteren Korsmeyer-Peppas, Peppas-Sahlin ve Weibull modelleri ile birden fazla modele uyduğunu göstermiştir.

Anahtar Kelimeler

• Akciğer kanseri
• kitosan
• paklitaksel
• polikaprolakton
• poli-l-lizin

PACLITAXEL-LOADED POLYCAPROLACTONE NANOPARTICLES FOR LUNG TUMORS; FORMULATION, COMPREHENSIVE IN VITRO CHARACTERIZATION AND RELEASE KINETIC STUDIES

Öz

Objective: Today, cancer is still among the most common chronic diseases. Nanoparticular drug delivery systems prepared with biocompatible and biodegradable polymers such as polycaprolactone are rational solution for anticancer agents with poor solubility and low bioavailability. The aim of this study is to prepare paclitaxel-loaded polycaprolactone nanoparticles, which is known to be a potent anticancer, and to elucidate in vitro characteristics and release kinetic mechanisms.
Material and Method: It was aimed to prepare paclitaxel-loaded polycaprolactone nanoparticles by nanoprecipitation. Preformulation studies were carried out with different molecular weights of polycaprolactone (Mw: 14.000, Mw: 80.000). Nanoparticles were coated with Chitosan or Poly-l-lysine to obtain cationic surface charge and to increase cellular interaction. Comprehensive characterization of formulations and release kinetic studies were performed.
Result and Discussion: The particle size of the formulations ranged from 188 nm to 383 nm. Encapsulation efficiency increased to 77% in different formulations. SEM analysis confirmed the nanoparticles were spherical. Within the scope of in vitro release studies, the release continued for up to 96 hours and less than 50% of the therapeutic load was released in the first 24 hours. Mathematical modeling indicated that the release kinetics fit more than one model with the Korsmeyer-Peppas, Peppas-Sahlin and Weibull models, which show high correlation.

Anahtar Kelimeler

• Chitosan
• lung cancer
• paclitaxel
• polikaprolakton
• poly-l-lysine

Kaynakça

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