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In-Vitro Test and Mathematical Modeling on The Controlled-Release Behavior of Indomethacin from PLA-PEO Nanospheres

Y S Jo, M Kim, D K Kim, C J Kim, J K Jeong, K J Kim, M Muhammed

Ann Transplant 2004; 9(1A): 96-100

ID: 15646


Objectives: Drug delivery systems (DDS) have been focused on as the most effective way to administer highly insoluble drug under physiological conditions to the targeted site in a controlled manner. Here, we report the synthesis of poly (lactic acid-co-ethylene oxide) (PLA-PEO), fabrication of PLA-PEO amphiphilic DDS and investigations of releasing behaviours of indomethacin as a model drug.
Methods: Sn (II) 2-ethylhexanoate was used to polymerize poly (L-lactide) (PLLA) with poly (ethylene glycol) (PEG) via ring-opening polymerization (ROP). The emulsion/evaporation technique was used to produce amphiphilic nanospheres and resulted in a homogeneous size distribution with a low polydispersity index. Under physiologically similar conditions, an in vitro test was conducted via a dialysis method in phosphate saline buffer solution (PBS).
Results: 1H-NMR, DSC and XRD analysis indicated that PLLA-PEO copolymer was successfully synthesized. Moreover, a QELS particle sizer
showed the spheres were well-defined with a narrow distributional character. As for the in vitro experiments, the releasing behaviours of
indomethacin were well explained by two different types of mathematical models constructed, including diffusion and dissolution models.
Conclusions: It was confirmed that key parameters such as volumetric ratio (Vr) between the organic and aqueous phases, the interaction parameter (Kp), and encapsulation efficiency (EE), affected to the overall characteristics of the controlled-release of the encapsulated drug. As the system had higher Vr value, the releasing profile tended to move toward the dissolution model, so that overall efficiencies (ζ) were evaluated to optimize the DDS for a specific type of drug or materials under consideration of various parameters to be manipulated.

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