title: Carboplatin loaded Surface modified PLGA nanoparticles: Optimization, characterization, and in vivo brain targeting studies.
abstract: The carboplatin (CP) loaded poly-lactide-co-glycolide (PLGA) nanoparticles (NPs) were formulated by modified solvent evaporation method. Its surface modification is done by 1% polysorbate80 (P80) to improve their entry into the brain after intraperitoneal administration (i.p) via receptor-mediated pathways. A formulation with maximum entrapment efficiency and minimal particle size was optimized by central composite design (CCD) based on mean particle size, and entrapment efficiencies as responses. The optimized formulation was characterized by mean particle size, entrapment efficiency, zeta potential, Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) analysis. The surface modified NPs were analysed for mean particle, zeta potential, FTIR, and in vitro release studies. The spherical particles with mean particle size 161.9nm, 162.4nm and zeta potential value of -26.5, -23.9 were obtained for unmodified and surface modified NPs respectively. The in vitro release experiments of the surface modified PLGA NPs exhibited sustained release for more than 48h, which was in accordance with Higuchi's equation with Fickian diffusion-based release mechanism. The in vivo bio distribution of P80 coated CP loaded PLGA NPs was compared with CP solution, and CP loaded NPs, in adult wistar rats. In the brain, compared with CP solution, both types of NPs especially NPs coated with P80 increased the concentration of carboplatin by 3.27 fold. All these results suggest that the developed formulation may improve the targeted therapy for malignant brain tumors in future.
authors.affiliation: Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kerala 686 631, India. Electronic address: sajanjose@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Jose
authors.affiliation: Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kerala 686 631, India.
authors.forename: B C
authors.initials: BC
authors.lastname: Juna
authors.affiliation: Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kerala 686 631, India.
authors.forename: T A
authors.initials: TA
authors.lastname: Cinu
authors.affiliation: Department of Pharmaceutical Sciences, Mahatma Gandhi University, Cheruvandoor Campus, Ettumanoor, Kerala 686 631, India.
authors.forename: H
authors.initials: H
authors.lastname: Jyoti
authors.affiliation: Caritas College of Pharmacy, Thellakom, Kerala, India.
authors.forename: N A
authors.initials: NA
authors.lastname: Aleykutty
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D016190:Carboplatin / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D004705:Endocytosis / Q000502:physiology; D005163:Factor Analysis, Statistical; D007274:Injections, Intraperitoneal; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011136:Polysorbates / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D011136:Polysorbates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016190:Carboplatin
keywords: Brain targeting; Carboplatin; Nanoparticles; Poly-lactide-co-glycolide; Polysorbate80