title: Preparation and investigation of sustained drug delivery systems using an injectable, thermosensitive, in situ forming hydrogel composed of PLGA-PEG-PLGA.
abstract: In situ gelling systems are very attractive for pharmaceutical applications due to their biodegradability and simple manufacturing processes. The synthesis and characterization of thermosensitive poly(D,L-lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-PLGA triblock copolymers as in situ gelling matrices were investigated in this study as a drug delivery system. Ring-opening polymerization using microwave irradiation was utilized as a novel technique, and the results were compared with those using a conventional method of polymerization. The phase transition temperature and the critical micelle concentration (CMC) of the copolymer solutions were determined by differential scanning calorimetry and spectrophotometry, respectively. The size of the micelles was determined with a light scattering method. In vitro drug release studies were carried out using naltrexone hydrochloride and vitamin B12 as model drugs. The rate and yield of the copolymerization process via microwave irradiation were higher than those of the conventional method. The copolymer structure and concentration played critical roles in controlling the sol-gel transition temperature, the CMC, and the size of the nanomicelles in the copolymer solutions. The rate of drug release could be modulated by the molecular weight of the drugs, the concentration of the copolymers, and their structures in the formulations. The amount of release versus time followed zero-order release kinetics for vitamin B12 over 25 days, in contrast to the Higuchi modeling for naltrexone hydrochloride over a period of 17 days. In conclusion, PLGA-PEG1500-PLGA with a lactide-to-glycolide ratio of 5:1 is an ideal system for the long-acting, controlled release of naltrexone hydrochloride and vitamin B12.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Elham
authors.initials: E
authors.lastname: Khodaverdi
authors.forename: Farnaz Sadat Mirzazadeh
authors.initials: FS
authors.lastname: Tekie
authors.forename: Seyed Ahmad
authors.initials: SA
authors.lastname: Mohajeri
authors.forename: Fariba
authors.initials: F
authors.lastname: Ganji
authors.forename: Gholamhossein
authors.initials: G
authors.lastname: Zohuri
authors.forename: Farzin
authors.initials: F
authors.lastname: Hadizadeh
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D007267:Injections; D007700:Kinetics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008872:Microwaves; D008956:Models, Chemical; D015394:Molecular Structure; D008970:Molecular Weight; D009271:Naltrexone / Q000008:administration & dosage / Q000737:chemistry*; D053758:Nanoparticles; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis*; D011098:Polyglactin 910 / Q000138:chemical synthesis*; D058105:Polymerization; D012542:Scattering, Radiation; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000737:chemistry*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D008823:Micelles; D009292:Narcotic Antagonists; C528571:poly(lactic-co-glycolic acid)-polyethylene glycol-poly(lactic-co-glycolic acid); D014803:Vitamin B Complex; D011098:Polyglactin 910; D011092:Polyethylene Glycols; D009271:Naltrexone; D014805:Vitamin B 12