Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil.
The present investigation was aimed to develop and explore the prospective of engineered PLGA nanoparticles as vehicles for targeted delivery of 5-fluorouracil (5-FU). Nanoparticles of 5-FU-loaded hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA-FU) copolymer were prepared and characterized by FTIR, NMR, transmission electron microscopy, particle size analysis, DSC, and X-ray diffractometer measurement studies. The nanoparticulate formulation was evaluated for in vitro release, hemolytic toxicity, and hematological toxicity. Cytotoxicity studies were performed on Ehrlich ascites tumor (EAT) cell lines using MTT cell proliferation assay. Biodistribution studies of 99m Tc labeled formulation were conducted on EAT-bearing mice. The in vivo tumor inhibition study was also performed after i.v. administration of HA-PEG-PLGA-FU nanoparticles. The HA conjugated formulation was found to be less hemolytic but more cytotoxic as compared to free drug. The hematological data suggested that HA-PEG-PLGA-FU formulation was less immunogenic compared to plain drug. The tissue distribution studies displayed that HA-PEG-PLGA-FU were able to deliver a higher concentration of 5-FU in the tumor mass. In addition, the HA-PEG-PLGA-FU nanoparticles reduced tumor volume significantly in comparison with 5-FU. Thus, it was concluded that the conjugation of HA imparts targetability to the formulation, and enhanced permeation and retention effect ruled out its access to the non-tumor tissues, at the same time favored selective entry in tumors, thereby reducing the side-effects both in vitro and in vivo.
Yadav
Awesh K
AK
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar, India.
Agarwal
Abhinav
A
Rai
Gopal
G
Mishra
Pradeep
P
Jain
Sanyog
S
Mishra
Anil K
AK
Agrawal
Himanshu
H
Agrawal
Govind P
GP
D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry; D019344:Lactic Acid / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D051379:Mice; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D018675:Toxicity Tests; D014961:X-Ray Diffraction
D001672:Biocompatible Materials; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006820:Hyaluronic Acid; D005472:Fluorouracil