title: 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.
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, India.
authors.forename: Vamshikrishna
authors.initials: V
authors.lastname: Karanam
authors.affiliation: Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga 4710-057, Portugal.
authors.forename: Gregory
authors.initials: G
authors.lastname: Marslin
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, India. Electronic address: bala.k.2006@gmail.com.
authors.forename: Balakumar
authors.initials: B
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, India.
authors.forename: Vijayaraghavan
authors.initials: V
authors.lastname: Chellan
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, India.
authors.forename: Karthik
authors.initials: K
authors.lastname: Siram
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, India.
authors.forename: Tamilselvan
authors.initials: T
authors.lastname: Natarajan
authors.affiliation: Department of Pharmacology, PSG College of Pharmacy, Coimbatore 641004, India.
authors.forename: Balaji
authors.initials: B
authors.lastname: Bhaskar
authors.affiliation: Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga 4710-057, Portugal.
authors.forename: Gregory
authors.initials: G
authors.lastname: Franklin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002208:Caproates / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry*; D051381:Rats
chemical_list: D000970:Antineoplastic Agents; D002208:Caproates; D007783:Lactones; D011108:Polymers; C121056:caprolactone; D016190:Carboplatin; D016650:Fluorescein-5-isothiocyanate
keywords: Carboplatin; Haemolysis; In vitro cytotoxicity; Poly (ɛ-caprolactone) nanoparticles; U-87 MG