Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells

• Published in: Drug development and industrial pharmacy 2012-09, Vol.38 (9), p.1107-1116
• Main Authors: engel-Türk, C. Tuba, Hasçiçek, Canan, Dogan, A. Lale, Esendagli, Gunes, Guc, Dicle, Gönül, Nur in
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Biological Transport; Cell Survival - drug effects; Chemistry, Pharmaceutical; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; cyclooxygenase-2; cytotoxicity; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - metabolism; Drug Carriers - pharmacology; Drug Stability; HT29 Cells; Humans; Kinetics; Lactic Acid - chemistry; Molecular Weight; Nanoparticles; Nanoparticles - chemistry; Particle Size; PLGA; Polyglycolic Acid - chemistry; Polyvinyl Alcohol - analysis; PVA; Solubility; Surface Properties; Thiazines - administration & dosage; Thiazines - chemistry; Thiazines - metabolism; Thiazines - pharmacology; Thiazoles - administration & dosage; Thiazoles - chemistry; Thiazoles - metabolism; Thiazoles - pharmacology; uptake
• ISSN: 0363-9045; 1520-5762
• DOI: 10.3109/03639045.2011.641562

Context: 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. Conclusion: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.