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Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a Potential Anticancer Drug Delivery System

Patel, Meghavi

Abstract Details

2012, Master of Science in Pharmaceutical Science (MSP), University of Toledo, College of Pharmacy.
Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core with a well-defined shell and the particle size was in agreement with the particle size analysis data obtained by DLS. DSC thermograms of the lyophilized SLNs indicate a reduction in the crystallinity order of GMS particles. The drug encapsulation efficiency was found to be approximately 30%. In vitro drug release studies from redispersed lyophilized SLNs showed that 17 % of the encapsulated drug was released within 2 h. The SLNs prepared in our lab demonstrated characteristics that can potentially be utilized in an anticancer drug delivery system. Future in vitro cell culture and in vivo animal model studies will delineate compatibility and utility of these formulations in biological systems.
Jerry Nesamony, PhD (Committee Chair)
Sai Hanuman Sagar Boddu, PhD (Committee Member)
Surya Nauli, PhD (Committee Member)
95 p.

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Citations

  • Patel, M. (2012). Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a Potential Anticancer Drug Delivery System [Master's thesis, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1352944517

    APA Style (7th edition)

  • Patel, Meghavi. Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a Potential Anticancer Drug Delivery System. 2012. University of Toledo, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1352944517.

    MLA Style (8th edition)

  • Patel, Meghavi. "Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a Potential Anticancer Drug Delivery System." Master's thesis, University of Toledo, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=mco1352944517

    Chicago Manual of Style (17th edition)