Poly (DL-Lactic-Co-Glycolic Acid) Microparticle- Doxorubicin Formulations for Anti-cancer Drug Delivery

Yıl 2014, Cilt: 73 Sayı: 1, 9 - 19, 27.11.2014

Gülseren Çağlar Serap Yalçın Güngör Gündüz Ufuk Gündüz

Öz

Cancer is a group of diseases in which normal cells are converted to cells capable of autonomous growth
and invasion. In the chemotherapeutic control of cancer, drugs are usually given systemically so they reach
toxic levels in cancer cells. This causes serious side effects in healthy cells. Another important problem with
chemotherapy is resistance developed to cytotoxic drugs (multi drug resistance). As a possible solution to
these problems, in the present study, two different microparticle fabrication methods were compared; double
emulsion solvent evaporation (SE) method for encapsulation of Doxorubicin into PLGA microparticles.
The most appropriate method was the SE techniquies which lead to higher encapsulation efficiencies.
Processing factors were evaluated for their effects on encapsulation efficiency and results indicated that
any change that hinder drug diffusion would result in increased drug content in microparticles. To asses
the cytotoxicities of synthesized microparticles, cell proliferation assays were performed with XTT reagent
on Doxorubicin resitant and sensitive breast cancer cell lines, MCF-7. DOX entrapped microparticles was
effective on both sensitive and DOX resistant MCF-7 cells. The concentration of drug in resistant cancer
cells was increased indicating a partial reversal of drug resistance. The results of this study will provide
new insights to the development of new drug delivery systems for cancer therapy.

Anahtar Kelimeler

PLGA, DOX, MCF-7, microparticle, drug delivery.

Anti-kanser İlaç Taşınması için Doksorubisin-Poli (DL-Laktik- Ko-Glikolik Asit) Mikroparçacıklarının Formülasyonları

Öz

Kanser, hücrelerin kontrolsuz çoğalma ve yayılma özelliği kazandığı bir hastalıktır. Kanserin kemoterapi ile tedavisinde ilaçlar genelde sistemik olarak verilir ve kanser hücrelerinde toksik etkiye ulaşır. Ancak kanserli hücrelerin yanı sıra sağlıklı hücrelerde de ilaç seviyesi toksik düzeylere ulaştığında ciddi yan etkilere neden olmaktadır. Kemoterapi ile ilgili bir başka önemli problemde anti-kanser ilaçlara karşı gelişen dirençliliktir (çoklu ilaç dirençliliği). Bu problemleri çözmek için, çalışmada iki farklı mikroparçacık üretim metodu karşılaştırılmıştır; PLGA mikroparçacıklarının içine, Doksorubisin tekli emulsiyon çözücü buharlaştırma (SE) yöntemi ile tutuklanmıştır. En yüksek ilaç tutuklanma yüzdesi SE tekniği ile elde edilmiştir. Sentezlenen mikroparçacıklar sitotoksisitesini belirlemek için, hücre çoğalma testi, XTT kullanılarak Doksorubisin dirençli ve duyarlı meme kanseri hücre hatlarında, MCF-7, kullanılmıştır. Doksorubisin tutuklanmış mikroparçacıklar hem duyarlı hemde Doksorubisin dirençli MCF-7 hücrelerinde etkili olmuştur. Dirençli kanser hücrelerinde ilacın konsantrasyonu kısmi olarak ilaç dirençliliğinin geri çevrilmesini artırmıştır. Bu çalışmanın sonuçları, kanser tedavisi için yeni ilaç taşıma sistemlerinin geliştirilmesine katkı sağlayacaktır.

Anahtar Kelimeler

PLGA, Doksorubisin, MCF-7, mikroparçacık, ilaç taşınması

Kaynakça

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