title: Chondroitin sulphate decorated nanoparticulate carriers of 5-fluorouracil: development and in vitro characterization.
abstract: The present study investigates prospective of tailored nanoparticles as vectors to provide improved therapeutic efficacy of encapsulated anti-cancer drug 5-FU. Condritin Sulphate (CS) conjugated PLGA nanoparticles were prepared using PEG-bis-amine and adipic dihydrazide as spacers and loaded with an anti-cancer drug 5-FU (CS-PEG-PLGA-FU and CS-ADH-PLGA-FU). The formulations were then compared with non CS-anchored monomethoxy(polyethylene glycol) (MPEG-PLGA-FU) nanoparticles. Nanoparticlulate systems were further characterized by FTIR, NMR, TEM studies and particle size/polydispersity index (PDI) analysis. DSC and XRD were also performed to assess the nature of 5-FU inside the nanoparticles. The nanoparticles prepared using amphiphilic block copolymer CS-PEG-PLGA were able to sustain the release of 5-FU up to 48 h whereas those of CS-ADH-PLGA and MPEG-PLGA released the drug up to 24 h. The CS-PEG-PLGA-FU nanoparticles were found to be least haemolytic when compared to free drug, CS-ADH-PLGA-FU and MPEG-PLGA-FU nanoparticles. Cytotoxicity studies were performed on MCF-7/MDA-MD 231 breast cancer cells. PLGA nanoparticles exhibited more potent cytotoxic effect on MCF-7/MDA-MD 231 cells than free doxorubicin. Further, enhanced cytotoxicity and lower hemolytic potential of CS-PEG-PLGA-FU nanoparticles suggest a potential application in cancer chemotherapy.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University Sagar (M.P.) 470003, India.
authors.forename: Awesh K
authors.initials: AK
authors.lastname: Yadav
authors.forename: Abhinav
authors.initials: A
authors.lastname: Agarwal
authors.forename: Sanyog
authors.initials: S
authors.lastname: Jain
authors.forename: Anil K
authors.initials: AK
authors.lastname: Mishra
authors.forename: Hemant
authors.initials: H
authors.lastname: Bid
authors.forename: Gopal
authors.initials: G
authors.lastname: Rai
authors.forename: Hirnanshu
authors.initials: H
authors.lastname: Agrawal
authors.forename: Govind P
authors.initials: GP
authors.lastname: Agrawal
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D005472:Fluorouracil / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014961:X-Ray Diffraction
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D002809:Chondroitin Sulfates; D005472:Fluorouracil