title: Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells.
abstract: BACKGROUND
  The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.
  
  
  OBJECTIVE
  In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.
  
  
  METHODS
  NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.
  
  
  RESULTS
  NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.
  
  
  CONCLUSIONS
  The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Ankara University, Tandogan, Ankara, Turkey.
authors.forename: C Tuba
authors.initials: CT
authors.lastname: Şengel-Türk
authors.forename: Canan
authors.initials: C
authors.lastname: Hasçiçek
authors.forename: A Lale
authors.initials: AL
authors.lastname: Dogan
authors.forename: Gunes
authors.initials: G
authors.lastname: Esendagli
authors.forename: Dicle
authors.initials: D
authors.lastname: Guc
authors.forename: Nurşin
authors.initials: N
authors.lastname: Gönül
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004355:Drug Stability; D019073:HT29 Cells; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D000077239:Meloxicam; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000032:analysis; D012995:Solubility; D013499:Surface Properties; D013843:Thiazines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D013843:Thiazines; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol; D000077239:Meloxicam