Research ArticlesPolymer–drug compatibility: A guide to the development of delivery systems for the anticancer agent, ellipticine
Section snippets
INTRODUCTION
Compatibility between a drug and polymer is known to be one of the key factors in determining the effectiveness of polymeric delivery systems. Herein we consider compatibility between a polymer and drug to refer to miscibility and/or interaction with no alteration in the chemical structure of the polymer or the drug. Because each drug has its own unique chemical and physical properties, no delivery vehicle prepared from a particular polymer will serve as a universal carrier for all drugs. The
Materials
Ellipticine, polycaprolactone (MW = 14,000), poly (d,l‐lactide) (MW = 75,000–120,000), poly (glycolide) (MW = 100,000–125,000), poly‐β‐benzyl‐L‐aspartate (MW = 11,500) and all solvents (HPLC grade) were purchased from Sigma‐Aldrich Chemical Company (St. Louis, MO). The block copolymers, poly (ethylene oxide)‐b‐polycaprolactone (with MW = 5000 for poly (ethylene oxide) and 4000 for polycaprolactone, i.e., PEO5000‐b‐PCL4000) and poly (ethylene oxide) b‐poly (d,l‐lactide) (with MW = 5000 for poly
Calculations and Comparison of Solubility Parameters
Table 1 includes the values we obtained for the partial solubility parameters for Ellipticine and various polymers calculated by GCM. The value for the total solubility parameter for Ellipticine (δt = 26.09) was very close to that obtained using Molecular Modeling Pro software (Chem SW Inc.) (data not shown). Thermodynamic criteria for the mutual miscibility of two substances is based on the free energy of mixing (ΔGM); that is, if ΔGM is negative, the two substances are said to be mutually
CONCLUSION
Our studies have shown that consideration of partial solubility parameters and calculation of ΔHM enables prediction of polymer–drug compatibility. The X‐ray analyses of polymer–drug blends clearly provided an indication of which polymer was most suitable for Ellipticine.
The formulation studies including preparation of homopolymer films and copolymer micelles, demonstrated that consideration of solubility parameters and physico‐chemical analyses may be used to choose a suitable polymer for a
Acknowledgements
The authors would like to thank Professor R. MacGregor for allowing J. Liu to use his fluorometer, Professor E. Kumacheva for allowing J. Liu to use dynamic light scattering instrument. The authors are also grateful to NSERC and the University of Toronto Rosenstadt Fund for funding this research.
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