Regulation of Particle Morphology of pH-Dependent Poly(-caprolactone)-Poly(-glutamic acid) Micellar Nanoparticles to Combat Breast Cancer Cells

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Abstract:

The advantage of polymeric drug carriers lies in the uptake of the polymer nanoparticles by cancer cells before they release the drug, thereby reducing its toxic effects on healthy cells. A poly(-glutamic acid)-b-poly(-caprolactone)-b-poly(-glutamic acid) block copolymer was synthesized to encapsulate the anti-cancer drug doxorubicin in the treatment of wild type human breast cancer cells (MCF-7/WT). This pH-controllable carrier is negatively-charged in the presence of healthy tissues leading to lower cellular uptake. On the other hand, it becomes more hydrophobic in the acidic environment of cancer tissues, increasing its cellular uptake through the lipid bilayer. The block copolymer was characterized using Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, differential scanning calorimetry and dynamic light scattering. The micelles formed at a critical concentration range of 62–130 g/mL depending on the composition of poly(-glutamic acid) and poly(-caprolactone) chains. The nano-sized micelles were found to have pH-dependent sizes in the range of 90–200 nm. The role of poly(-glutamic acid) was to increase the hydrophilicity and decrease the particle size of the copolymer. The structures of micelles that were more compact and less anionic showed better stability in plasma. It was found that the drug loading content and drug loading efficiency were 12.14% and 97.22% respectively. The copolymer showed shrinking and aggregation at low pH which led to a slower drug release. These nano-sized micelles showed potential as effective drug delivery carriers for doxorubicin because of its accumulation and slow release inside the MCF-7/WT cells.

Keywords: BREAST CANCER; NANOPARTICLES; PH-DEPENDENCE; POLY(EPSI-CAPROLACTONE); POLY(GAMMA-GLUTAMIC ACID)

Document Type: Research Article

DOI: http://dx.doi.org/10.1166/jnn.2010.2536

Publication date: October 1, 2010

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  • Journal for Nanoscience and Nanotechnology (JNN) is an international and multidisciplinary peer-reviewed journal with a wide-ranging coverage, consolidating research activities in all areas of nanoscience and nanotechnology into a single and unique reference source. JNN is the first cross-disciplinary journal to publish original full research articles, rapid communications of important new scientific and technological findings, timely state-of-the-art reviews with author's photo and short biography, and current research news encompassing the fundamental and applied research in all disciplines of science, engineering and medicine.
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