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Poly (ɛ-caprolactone) nanoparticles of carboplatin: Preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines.

Abstract
Carboplatin is a platinum based drug used in the treatment of several malignancies. Due to poor cellular uptake, generally, a larger dose of drug is administered to achieve therapeutic levels, causing harmful side-effects such as hematologic toxicity. In order to enhance the cellular uptake of carboplatin, we have developed carboplatin loaded nanoparticles using the biodegradable polymer poly (ɛ-caprolactone) (PCL). Nanoparticles ranging from the size of 23.77±1.37 to 96.73±2.79 nm with positive zeta potential and moderate entrapment efficiency (54.21±0.98%) were obtained. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the spherical morphology and smooth surface of all nanoformulations. The concentrations of PCL and the stabilizer (DMAB) are found to play a role in determining the size and the entrapment efficiency of the nanoparticles. Drug release from nanoparticles followed a biphasic pattern with an initial burst release followed by a sustained release for 10h. Results of in vitro cellular uptake and cytotoxicity studies revealed that carboplatin in the form of PCL-nanoparticles were efficiently up taken and displayed profound cytotoxicity to U-87 MG (human glioma) cells than the free drug. Importantly, unlike the free carboplatin, carboplatin in the form of PCL nanoparticles did not present any haemolytic activity in rat erythrocytes, a major side effect of this chemotherapeutic drug. This suggests that poly (ɛ-caprolactone) nanoencapsulation of carboplatin might be an efficient approach to treat cancer, while reducing carboplatin induced haemolysis.
AuthorsVamshikrishna Karanam, Gregory Marslin, Balakumar Krishnamoorthy, Vijayaraghavan Chellan, Karthik Siram, Tamilselvan Natarajan, Balaji Bhaskar, Gregory Franklin
JournalColloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 130 Pg. 48-52 (Jun 01 2015) ISSN: 1873-4367 [Electronic] Netherlands
PMID25899843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Caproates
  • Lactones
  • Polymers
  • caprolactone
  • Carboplatin
  • Fluorescein-5-isothiocyanate
Topics
  • Animals
  • Antineoplastic Agents (chemistry, pharmacokinetics, pharmacology)
  • Caproates (chemistry)
  • Carboplatin (chemistry, pharmacokinetics, pharmacology)
  • Cell Line
  • Cell Survival (drug effects)
  • Fluorescein-5-isothiocyanate (chemistry)
  • Hemolysis (drug effects)
  • Humans
  • Lactones (chemistry)
  • Microscopy, Atomic Force
  • Microscopy, Electron, Transmission
  • Nanoparticles (chemistry, ultrastructure)
  • Polymers (chemistry)
  • Rats

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