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      • HARVEST
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      DEVELOPMENT OF ONCE-DAILY MYCOPHENOLATE MOFETIL SUSTAINED RELEASE ORAL NANOPARTICLES

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      MOHAMMED-THESIS-2017.pdf (3.927Mb)
      Date
      2018-10-01
      Author
      Mohammed, Munawar Ali 1989-
      ORCID
      0000-0003-0504-8962
      Type
      Thesis
      Degree Level
      Masters
      Metadata
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      Abstract
      Objective: To develop an oral sustained release formulation of the immunosuppressive drug, mycophenolate mofetil (MMF) for once-daily dosing, for use in organ transplant recipients as an anti-rejection drug. Formulating mucoadhesive chitosan-coated polymeric nanoparticles (CS-PNPs) of MMF presents a novel strategy for achieving sustained drug release of an essential drug for transplant patients, which could improve medication adherence and therefore transplant outcomes. Methods: MMF CS-PNPs were prepared by a single emulsion solvent evaporation method in chloroform with slight modifications. All the formulations are evaluated for particle size, encapsulation efficiency as well as in vitro drug release in USP simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Differential scanning calorimetry (DSC), surface morphology by scanning electron microscopy (SEM), and in vitro mucin binding of the nanoparticles were performed for further characterization. Results: Two optimal formulations [MMF: PLA: MMWC= 1:7:7 and MMF: HMWPLGA: HMWC= 1:7:7] had high encapsulation efficiency (94.34% and 75.44% respectively) and sustained drug release with a minimal burst phase. DSC experiments reveal an amorphous form of MMF in the nanoparticle formulations. The surface morphology of CS-PNPs observed by SEM showed spherical nanoparticles with minimal visible porosity. Mucin binding was assessed by changes in zeta potential after incubation of the nanoparticles in mucin. Conclusion: Two CS-PNP formulations; MMF: HMWPLGA: HMWC= 1:7:7 (w/w/w) and MMF: PLA: MMW= 1:7:7(w/w/w) had high drug loading and sustained drug release of MMF, representing lead candidates in the effort to design a once-daily dosage form for MMF.
      Degree
      Master of Science (M.Sc.)
      Department
      Pharmacy and Nutrition
      Program
      Pharmacy
      Committee
      Blackburn, Dave; El-Aneed, Anas; Badea, Ildiko; Mansell, Holly; Taghibiglou, Changiz
      Copyright Date
      October 2017
      URI
      http://hdl.handle.net/10388/11222
      Subject
      mycophenolate mofetil, polymeric nanoparticle, sustained-release, mucoadhesive
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