Preparation and Investigation of Sustained Drug Delivery Systems Using an Injectable, Thermosensitive, In Situ Forming Hydrogel Composed of PLGA–PEG–PLGA
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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.
KEY WORDShydrogel naltrexone PLGA–PEG–PLGA thermosensitive triblock copolymer vitamin B12
The authors are grateful for the financial support provided by Mashhad University of Medical Sciences for this study. The results described in this paper were part of a Pharm D student’s thesis proposal.
- 1.Khodaverdi E, Rajabi O, Farhadi F, Jalali A, Mirzazadeh Tekie FS. Preparation and investigation of (N-isopropylacrylamide-acrylamide) membranes in temperature responsive drug delivery. Iran J Basic Med Sci. 2009;13:1–8.Google Scholar
- 11.McGregor C, Ali R, White JM, Thomas P, Gowing L. A comparison of antagonist-precipitated withdrawal under anesthesia to standard inpatient withdrawal as a precursor to maintenance naltrexone treatment in heroin users: outcomes at 6 and 12 months. Drug Alcohol Depend. 2002;68:5–14.PubMedCrossRefGoogle Scholar
- 13.Smith K, Hopp M, Mundin G, Leyendecker P, Bailey P, Grothe B, Uhl R, Reimer K. Single- and multiple-dose pharmacokinetic evaluation of oxycodone and naloxone in an opioid agonist/antagonist prolonged-release combination in healthy adult volunteers. Clin Ther. 2008;30:2051–68.PubMedCrossRefGoogle Scholar