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Intra-articular Extended-Release Drug Delivery System for Arthritis Treatment

Mianabadi, Fatemeh | 2021

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 58433 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Abdkhodaei, Mohammad Jafar; Akrami, Mohammad
  7. Abstract:
  8. Osteoarthritis is one of the most common cartilage-destroying diseases that causes pain and inflammation in joints such as the knee. Intra-articular sustained-release drug delivery systems are effective strategies to prevent the side effects of systemic drug use on other organs, control the rate of drug release at the injection site, and reduce the number of injections during treatment. In this study, polycaprolactone microparticles containing triamcinolone acetonide drug (TA-loaded PCL MPs) by single emulsion solvent evaporation method. In order to investigate the effect of two variables of polymer molecular mass and also the ratio of drug to polymer on particle size and drug encapsulation efficiency (EE%), PCL with 5 different molecular masses (65000, 45000, 14000, 10000 and 80000) and different ratios of drug to polymer (10:50, 10:100, 10:1150, 10:150 and 10:250 (mg/mg)) were used to fabricate the microparticles. In order to optimize the number of experiments and determine the optimal sample, we used the design expert software and the central composite design method. After fabrication of 11 microparticles proposed by the software, SEM test was performed to observe the structure and size of particles and drug encapsulation efficiency (EE%) was calculated by high performance liquid chromatography (HPLC). The sample made with a molecular mass of 45,000 and a drug to polymer ratio of 10:250 with a size of 6.5 μm and drug encapsulation efficiency of 86.66% was identified as the optimal sample. In order to improve the properties of the drug delivery system and control the initial burst release, selected microparticles were encapsulated in a thermo-sensitive hydrogel composed of 2% hyaluronic acid and methyl cellulose with three different concentrations of 4%, 9% and 14% with a volume ratio of 50:50 (HA:MC). The in vitro drug release study confirmed that the drug loaded microparticles suspended in hydrogel with a concentration of 14% methylcellulose (PCL MPs-HAMC18) released the 30% of the drug during 192 hours, with almost low burst effect. Also, the in vivo biocompatibility studies on rats proved no sign of cyst formation, inflammation or accumulation of macrophages in the groups which received PCL MPs-HAMC14%. Therefore, the designed system can be a promising choice for sustained drug delivery to the affected osteoarthritis joints
  9. Keywords:
  10. Osteoarthritis ; Drug Delivery ; Extended Release System ; Hyaluronic Acid Gel ; Hydrogel ; Microparticles ; Arthritis Rheumatoid

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