In-vitro test and mathematical modelling on the controlled-release behavior of indomethacin from PLA-PEO nanospheres

Yun-Suk Jo 1Min-Cheol Kim 2Do-Kyung Kim 1Charn-Jung Kim 2Young-Keun Jeong 3Kyung-Ja Kim 3Mamoun Muhammed 1

1. Royal Institute of Technology, Dept of Materials Science and Engineering, Materials Chemistry Division (KTH), Brinellvaegen 23, 2tr., Stockholm SE10044, Sweden
2. Seoul National University, School of Mechanical and Aerospace Engineering (SNU), Kwanak-gu Shillim-dong San 56-1, Seoul 151744, Korea, South
3. Korea Institute of Ceramic Engineering and Technology (KICET), , Gasang-Dong, Geumcheon-Gu, Seoul 153023, Korea, South

Abstract

Drug delivery systems (DDS) have been focused as the most effective way to administer highly insoluble drug under physiologic conditions to the targeted site in a controlled manner. We report the synthesis of poly(lactic acid-co-ethylene oxide) (PLA-PEO), fabrication of PLA-PEO amphiphilic DDS and investigations of releasing behaviors of indomethacin as a model drug. The ring-opening polymerization (ROP) is commonly used technique for the synthesis of well-defined homo/copolymers from lactones or lactides. Instead of Sn(II) 2-ethylhexanoate which is well-known initiator for the ROP, a bioresorbable substance Fe(II) lactate was used to polymerize poly(D,L-lactide) (PDLLA) and poly(L-lactide) (PLLA) with poly(ethylene glycol) (PEG) to yield a series of PLA-PEO amphiphilic copolymers in the different compositions. DSC and XRD analysis results indicated that all copolymers were successfully synthesized and especially Fe(II) lactate was revealed as an effective initiator to yield highly crystalline PLLA-PEO copolymers. Emulsion/evaporation technique was used to fabricate amphiphilic nanospheres and resulted in a homogeneous size distribution with a low polydispersity index. Under physiologically similar condition, in-vitro test was conducted via dialysis method in phosphate saline buffer solution (PBS). The releasing behaviors were compared to two different types of mathematical models including diffusion and dissolution models. It was confirmed that key parameters such as volumetric ratio (Vr) between organic and aqueous phase, interaction parameter (Kp), and encapsulation efficiency (EE), affected to the overall characteristic regarding controlled-release of the entrapped drug. As the system had higher Vr value, the releasing profile tended to move toward dissolution model so that overall efficiency (ζ) were evaluated to optimize DDS for a specific type of drug or materials under consideration of various parameters to be manipulated.

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Presentation: oral at E-MRS Fall Meeting 2003, Symposium E, by Yun-Suk Jo
See On-line Journal of E-MRS Fall Meeting 2003

Submitted: 2003-05-27 19:48
Revised:   2009-06-08 12:55
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