title: Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats.
abstract: The aim of this study was to assess the potential of nanoparticles to improve the pharmacokinetics of curcumin, with a primary goal of enhancing its bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a single-emulsion solvent-evaporation technique, resulting in particles size smaller than 200 nm. The encapsulation efficiency was over 70% for both formulations. The in vitro release study showed that curcumin was released more slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC-MS/MS method was developed and validated to quantify curcumin in rat plasma. The nanoparticles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with the curcumin aqueous suspension. It was observed that both nanoparticles formulations were able to sustain the curcumin delivery over time, but greater efficiency was obtained with the PLGA-PEG nanoparticles, which showed better results in all of the pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in approximately 4 and 6h, respectively, and the C(max) of curcumin increased 2.9- and 7.4-fold, respectively. The distribution and metabolism of curcumin decreased when it was carried by nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and 55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA-PEG blend nanoparticles are potential carriers for the oral delivery of curcumin.
authors.affiliation: Department of Pharmacy, Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava, PR, Brazil.
authors.forename: Najeh Maissar
authors.initials: NM
authors.lastname: Khalil
authors.forename: Thuane Castro Frabel
authors.initials: TC
authors.lastname: do Nascimento
authors.forename: Diani Meza
authors.initials: DM
authors.lastname: Casa
authors.forename: Luciana Facco
authors.initials: LF
authors.lastname: Dalmolin
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: de Mattos
authors.forename: Ivonete
authors.initials: I
authors.lastname: Hoss
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Romano
authors.forename: Rubiana Mara
authors.initials: RM
authors.lastname: Mainardes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004339:Drug Compounding; D005079:Excipients; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols; D011098:Polyglactin 910; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: D005079:Excipients; C102418:poly(lactic-glycolic acid)-poly(ethyleneglycol) copolymer; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D003474:Curcumin