title: Cellular uptake, antioxidant and antiproliferative activity of entrapped α-tocopherol and γ-tocotrienol in poly (lactic-co-glycolic) acid (PLGA) and chitosan covered PLGA nanoparticles (PLGA-Chi).
abstract: The aim of this study was to formulate and characterize α-tocopherol (α-T) and tocotrienol-rich fraction (TRF) entrapped in poly (lactide-co-glycolide) (PLGA) and chitosan covered PLGA (PLGA-Chi) based nanoparticles. The resultant nanoparticles were characterized and the effect of nanoparticles entrapment on the cellular uptake, antioxidant, and antiproliferative activity of α-T and TRF were tested. In vitro uptake studies in Caco2 cells showed that PLGA and PLGA-Chi nanoparticles displayed a greater enhancement in the cellular uptake of α-T and TRF when compared with the control without causing toxicity to the cells (p<0.0001). Furthermore, the cellular internalization of both PLGA and PLGA-Chi nanoparticles labeled with FITC was investigated by fluorescence microscopy; both types of nanoparticles were able to get internalized into the cells with reasonable amounts. However, PLGA-Chi nanoparticles showed significantly higher (3.5-fold) cellular uptake compared to PLGA nanoparticles. The antioxidant activity studies demonstrated that entrapment of α-T and TRF in PLGA and PLGA-Chi nanoparticles exhibited greater ability in inhibiting cholesterol oxidation at 48 h compared to the control. In vitro antiproliferative studies confirmed marked cytotoxicity of TRF on MCF-7 and MDA-MB-231 cell lines when delivered by PLGA and PLGA-Chi nanoparticles after 48 h incubation compared to control. In summary, PLGA and PLGA-Chi nanoparticles may be considered as an attractive and promising approach to enhance the bioavailability and activity of poorly water soluble compounds such as α-tocopherol and tocotrienols.
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Dr., Monroe, LA 71201, USA.
authors.forename: Saeed
authors.initials: S
authors.lastname: Alqahtani
authors.affiliation: Department of Biological and Agricultural Engineering, LSU Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Lacey
authors.initials: L
authors.lastname: Simon
authors.affiliation: Department of Biological and Agricultural Engineering, LSU Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Astete
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Dr., Monroe, LA 71201, USA.
authors.forename: Alaadin
authors.initials: A
authors.lastname: Alayoubi
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Dr., Monroe, LA 71201, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Dr., Monroe, LA 71201, USA.
authors.forename: Sami
authors.initials: S
authors.lastname: Nazzal
authors.affiliation: Department of Biological and Agricultural Engineering, LSU Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Yixiao
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Biological and Agricultural Engineering, LSU Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Dr., Monroe, LA 71201, USA. Electronic address: kaddoumi@ulm.edu.
authors.forename: Amal
authors.initials: A
authors.lastname: Kaddoumi
authors.affiliation: Department of Biological and Agricultural Engineering, LSU Agricultural Center, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: CSabliov@agcenter.lsu.edu.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Sabliov
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D002839:Chromans / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D002839:Chromans; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C013649:plastochromanol 8; D048271:Chitosan; D024502:alpha-Tocopherol
keywords: Chitosan; Nanoparticles; PLGA; Tocotrienols; α-Tocopherol