Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 70, Issue 2, Pages 522-530Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2008.05.013
Keywords
Particle size distribution; Zeta potential; Dextran microspheres; Hydrogels; Network properties; Injectability; Computer simulations
Categories
Funding
- SenterNovem [IS042016]
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This work describes the tailorability of the network properties of self-assembling hydrogels, based on ionic crosslinking between dextran microspheres. Copolymerization of hydroxyethyl methacrylate-derivatized dextran (dex-HEMA), emulsified in an aqueous poly(ethylene glycol) (PEG) solution, with methacrylic acid (MAA) OF dimethylaminoethyl methacrylate (DMAEMA) resulted in negatively or positively charged microspheres, respectively, at physiological pH. The monomer/HEMA ratio ranged between 6 and 57, resulting in microspheres with zeta (zeta)-potentials from -6 to -34 mV and +3 to +23 mV, for the monomers MAA and DMAEMA, respectively. By altering the emulsification procedure, microsphere batches with various sizes and size distributions were obtained. The aim of the research was to assess the effect of particle size (distribution) and charge on the network properties of the macroscopic hydrogels. The ability to tailor the mechanical properties such as strength and elasticity increases the potential of the hydrogels to be used in a variety of pharmaceutical applications. Additionally, the injectability of these self-assembling hydrogels was investigated. Injectability is an important feature of drug delivery systems, since it allows avoiding Surgery. Rheological analysis showed that an increasing surface charge of the microspheres led to stronger hydrogels. Relatively small microspheres (7 pm) with a narrow size distribution (99% smaller than 14 mu m) gave rise to stronger hydrogels when compared to larger microspheres of 20 pin with a broad distribution (99% smaller than 50 mu m). When small microspheres were combined with large microspheres of opposite charge, it was found that the strongest gels were obtained with 75% small and 25% large microspheres, instead of equal amounts (50/50) of positively and negatively charged microspheres. Computer modeling confirmed these findings and showed that the most favorable composition, related to the lowest potential energy, comprised of 75% small microspheres. Taking both charge and size effects into account, the storage moduli (G') of the almost fully elastic hydrogels could be tailored from 400 to 30,000 Pa. Injectability tests showed that hydrogels (G' up to 4000 Pa) composed of equal amounts of oppositely charged microspheres (-7 and +6 mV, average particle size 7 mu m) could be injected through 25G needles using a static load of 15 N, an ISO accepted value. In conclusion, a variety of options to control the network properties of macroscopic hydrogels are provided, related to the charge and particle size of the composing dextran microspheres. Furthermore, it is shown that the hydrogels are injectable, making them attractive candidates for a diversity of pharmaceutical applications. (C) 2008 Elsevier B.V. All rights reserved.
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