Development and characterization of hyaluronic acid-anchored PLGA nanoparticulate carriers of doxorubicin.
A novel hyaluronic acid-poly(ethylene glycol)-poly(lactide-co-glycolide) (HA-PEG-PLGA) copolymer was synthesized and characterized by infrared and nuclear magnetic resonance spectroscopy. The nanoparticles of doxorubicin (DOX)-loaded HA-PEG-PLGA were prepared and compared with monomethoxy(polyethylene glycol) (MPEG)-PLGA nanoparticles. Nanoparticles were prepared using drug-to-polymer ratios of 1:1 to 1:3. Drug-to-polymer ratio of 1:1 is considered the optimum formulation on the basis of low particle size and high entrapment efficiency. The optimized nanoparticles were characterized for morphology, particle size measurements, differential scanning calorimetry, x-ray diffractometer measurement, drug content, hemolytic toxicity, subacute toxicity, and in vitro DOX release. The in vitro DOX release study was performed at pH 7.4 using a dialysis membrane. HA-PEG-PLGA nanoparticles were able to sustain the release for up to 15 days. The tissue distribution studies were performed with DOX-loaded HA-PEG-PLGA and MPEG-PLGA nanoparticles after intravenous (IV) injection in Ehrlich ascites tumor-bearing mice. The tissue distribution studies showed a higher concentration of DOX in the tumor as compared with MPEG-PLGA nanoparticles. The in vivo tumor inhibition study was also performed after IV injection of DOX-loaded HA-PEG-PLGA nanoparticles up to 15 days. DOX-loaded HA-PEG-PLGA nanoparticles were able to deliver a higher amount of DOX as compared with MPEG-PLGA nanoparticles. The DOX-loaded HA-PEG-PLGA nanoparticles reduced tumor volume significantly as compared with MPEG-PLGA nanoparticles.
Yadav
Awesh Kumar
AK
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, India.
Mishra
Pradeep
P
Mishra
Anil K
AK
Mishra
Pushpa
P
Jain
Sanyog
S
Agrawal
Govind Prasad
GP
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000737:chemistry*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry*; D008422:Materials Testing; D008558:Melphalan / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007074:Immunoglobulin G; D011108:Polymers; C051713:antineoplastic agent K 18; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D006820:Hyaluronic Acid; D008558:Melphalan