Folic acid-decorated and PEGylated PLGA nanoparticles for improving the antitumour activity of 5-fluorouracil.
5-Fluorouracil (5-FU) is a broad spectrum cytotoxic agent being used in chemotherapy of malignancies. However, 5-FU shows a number of limitations like short half-life, non-selective biodistribution, and the development of drug resistances by tumour cells. It was investigated the potential use of folic acid-decorated and PEGylated poly(D,L-lactide-co-glycolide) nanoparticles (FOL-PEG-PLGA NPs) for the targeted delivery of 5-FU to colon and breast cancers. PEG-PLGA and FOL-PEG-PLGA conjugates were synthesized and characterized. NPs of PLGA, PEG-PLGA, and FOL-PEG-PLGA were prepared by nanoprecipitation under optimal formulation conditions. They were found to be haemocompatible, and exhibited negligible cytotoxicity in normal (CCD-18 and MCF-10A) and tumour (HT-29 and MCF-7) human cell lines. 5-FU loading capabilities were also defined, and the NPs exhibited an initial burst drug release followed by a sustained 5-FU release. In vitro cytotoxicity studies in folate-overexpressed HT-29 colon cancer cells and MCF-7 breast cancer cells demonstrated that the half maximal inhibitory concentration (IC50) of 5-FU-loaded FOL-PEG-PLGA NPs was approximately 4-fold less than that of the 5-FU-loaded PLGA NPs (p<0.05). Consequently, FOL-PEG-PLGA NPs could have great potential as a targeted 5-FU delivery system for colon and breast cancer treatment.
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Spain; Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, University of Damascus, Syria.
Mazen M
MM
El-Hammadi
Department of Applied Physics, Faculty of Sciences, University of Granada, Spain.
Ángel V
ÁV
Delgado
Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.
Consolación
C
Melguizo
Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain.
José C
JC
Prados
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Granada, Spain; Institute of Biopathology and Regenerative Medicine (IBIMER), University of Granada, Spain; Biosanitary Institute of Granada (ibs.GRANADA), Andalusian Health Service (SAS), University of Granada, Spain. Electronic address: jlarias@ugr.es.
José L
JL
Arias
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000494:pharmacology; D005492:Folic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D053758:Nanoparticles; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols; D005492:Folic Acid; D005472:Fluorouracil
5-Fluorouracil; Cancer chemotherapy; FOL-PEG-PLGA conjugate; Haemocompatibility; Ligand-receptor mediated drug delivery; Nanoprecipitation.