Delivery of Positively Charged Proteins Using Hyaluronic Acid Microgels
In this study, hyaluronic acid (HA) microgels were developed for the goal of protein delivery. First, a hyaluronic acid-tyramine conjugate (HA-TA) was synthesized with a degree of substitution of 13 TA moieties per 100 disaccharide units. Then, HA-TA microdroplets were produced using a water in oil emulsion method and crosslinked in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). Loading capacity and the release kinetics of lysozyme and BSA, as model proteins, were investigated. It was shown that lysozyme, a cationic protein, can be incorporated efficiently in the HA microgels, while the loading efficiency for BSA, as a negatively charged protein, is low. The release profile of lysozyme showed a sustained release over a period of one month. The results demonstrated that the HA-TA microgels are a good carrier for spatial delivery of cationic proteins for biomedical applications.
[1] F. Lee, J. E. Chung, and M. Kurisawa, "An injectable hyaluronic acid–tyramine hydrogel system for protein delivery," Journal of Controlled Release, vol. 134, pp. 186-193, 2009.
[2] H. Bysell, R. Månsson, P. Hansson, and M. Malmsten, "Microgels and microcapsules in peptide and protein drug delivery," Advanced drug delivery reviews, vol. 63, pp. 1172-1185, 2011.
[3] A. Pepe, P. Podesva, and G. Simone, "Tunable uptake/release mechanism of protein microgel particles in biomimicking environment," Scientific Reports, vol. 7, p. 6014, 2017.
[4] S. A. Agnihotri, N. N. Mallikarjuna, and T. M. Aminabhavi, "Recent advances on chitosan-based micro-and nanoparticles in drug delivery," Journal of controlled release, vol. 100, pp. 5-28, 2004.
[5] Z. Liu, Y. Jiao, Y. Wang, C. Zhou, and Z. Zhang, "Polysaccharides-based nanoparticles as drug delivery systems," Advanced drug delivery reviews, vol. 60, pp. 1650-1662, 2008.
[6] C. Luo, J. Zhao, M. Tu, R. Zeng, and J. Rong, "Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network," Materials Science and Engineering: C, vol. 36, pp. 301-308, 2014.
[7] X. Xu, A. K. Jha, R. L. Duncan, and X. Jia, "Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2," Acta biomaterialia, vol. 7, pp. 3050-3059, 2011.
[8] X. Jia, Y. Yeo, R. J. Clifton, T. Jiao, D. S. Kohane, J. B. Kobler, et al., "Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration," Biomacromolecules, vol. 7, pp. 3336-3344, 2006.
[9] J. K. Oh, D. I. Lee, and J. M. Park, "Biopolymer-based microgels/nanogels for drug delivery applications," Progress in Polymer Science, vol. 34, pp. 1261-1282, 2009.
[10] R. Jin, L. M. Teixeira, P. J. Dijkstra, C. Van Blitterswijk, M. Karperien, and J. Feijen, "Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran–hyaluronic acid conjugates for cartilage tissue engineering," Biomaterials, vol. 31, pp. 3103-3113, 2010.
[11] C. Wu, C. Böttcher, and R. Haag, "Enzymatically crosslinked dendritic polyglycerol nanogels for encapsulation of catalytically active proteins," Soft Matter, vol. 11, pp. 972-980, 2015.
[12] D. E. Kuehner, J. Engmann, F. Fergg, M. Wernick, H. W. Blanch, and J. M. Prausnitz, "Lysozyme net charge and ion binding in concentrated aqueous electrolyte solutions," The Journal of Physical Chemistry B, vol. 103, pp. 1368-1374, 1999.
[13] S. Ge, K. Kojio, A. Takahara, and T. Kajiyama, "Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: influence of the phase separation on protein adsorption patterns," Journal of biomaterials science. Polymer edition, vol. 9, p. 131, 1998.
[14] M. Kong and H. J. Park, "Stability investigation of hyaluronic acid based nanoemulsion and its potential as transdermal carrier," Carbohydrate polymers, vol. 83, pp. 1303-1310, 2011.
[1] F. Lee, J. E. Chung, and M. Kurisawa, "An injectable hyaluronic acid–tyramine hydrogel system for protein delivery," Journal of Controlled Release, vol. 134, pp. 186-193, 2009.
[2] H. Bysell, R. Månsson, P. Hansson, and M. Malmsten, "Microgels and microcapsules in peptide and protein drug delivery," Advanced drug delivery reviews, vol. 63, pp. 1172-1185, 2011.
[3] A. Pepe, P. Podesva, and G. Simone, "Tunable uptake/release mechanism of protein microgel particles in biomimicking environment," Scientific Reports, vol. 7, p. 6014, 2017.
[4] S. A. Agnihotri, N. N. Mallikarjuna, and T. M. Aminabhavi, "Recent advances on chitosan-based micro-and nanoparticles in drug delivery," Journal of controlled release, vol. 100, pp. 5-28, 2004.
[5] Z. Liu, Y. Jiao, Y. Wang, C. Zhou, and Z. Zhang, "Polysaccharides-based nanoparticles as drug delivery systems," Advanced drug delivery reviews, vol. 60, pp. 1650-1662, 2008.
[6] C. Luo, J. Zhao, M. Tu, R. Zeng, and J. Rong, "Hyaluronan microgel as a potential carrier for protein sustained delivery by tailoring the crosslink network," Materials Science and Engineering: C, vol. 36, pp. 301-308, 2014.
[7] X. Xu, A. K. Jha, R. L. Duncan, and X. Jia, "Heparin-decorated, hyaluronic acid-based hydrogel particles for the controlled release of bone morphogenetic protein 2," Acta biomaterialia, vol. 7, pp. 3050-3059, 2011.
[8] X. Jia, Y. Yeo, R. J. Clifton, T. Jiao, D. S. Kohane, J. B. Kobler, et al., "Hyaluronic acid-based microgels and microgel networks for vocal fold regeneration," Biomacromolecules, vol. 7, pp. 3336-3344, 2006.
[9] J. K. Oh, D. I. Lee, and J. M. Park, "Biopolymer-based microgels/nanogels for drug delivery applications," Progress in Polymer Science, vol. 34, pp. 1261-1282, 2009.
[10] R. Jin, L. M. Teixeira, P. J. Dijkstra, C. Van Blitterswijk, M. Karperien, and J. Feijen, "Enzymatically-crosslinked injectable hydrogels based on biomimetic dextran–hyaluronic acid conjugates for cartilage tissue engineering," Biomaterials, vol. 31, pp. 3103-3113, 2010.
[11] C. Wu, C. Böttcher, and R. Haag, "Enzymatically crosslinked dendritic polyglycerol nanogels for encapsulation of catalytically active proteins," Soft Matter, vol. 11, pp. 972-980, 2015.
[12] D. E. Kuehner, J. Engmann, F. Fergg, M. Wernick, H. W. Blanch, and J. M. Prausnitz, "Lysozyme net charge and ion binding in concentrated aqueous electrolyte solutions," The Journal of Physical Chemistry B, vol. 103, pp. 1368-1374, 1999.
[13] S. Ge, K. Kojio, A. Takahara, and T. Kajiyama, "Bovine serum albumin adsorption onto immobilized organotrichlorosilane surface: influence of the phase separation on protein adsorption patterns," Journal of biomaterials science. Polymer edition, vol. 9, p. 131, 1998.
[14] M. Kong and H. J. Park, "Stability investigation of hyaluronic acid based nanoemulsion and its potential as transdermal carrier," Carbohydrate polymers, vol. 83, pp. 1303-1310, 2011.
@article{"International Journal of Medical, Medicine and Health Sciences:78188", author = "Elaheh Jooybar and Mohammad J. Abdekhodaie and Marcel Karperien and Pieter J. Dijkstra", title = "Delivery of Positively Charged Proteins Using Hyaluronic Acid Microgels", abstract = "In this study, hyaluronic acid (HA) microgels were developed for the goal of protein delivery. First, a hyaluronic acid-tyramine conjugate (HA-TA) was synthesized with a degree of substitution of 13 TA moieties per 100 disaccharide units. Then, HA-TA microdroplets were produced using a water in oil emulsion method and crosslinked in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). Loading capacity and the release kinetics of lysozyme and BSA, as model proteins, were investigated. It was shown that lysozyme, a cationic protein, can be incorporated efficiently in the HA microgels, while the loading efficiency for BSA, as a negatively charged protein, is low. The release profile of lysozyme showed a sustained release over a period of one month. The results demonstrated that the HA-TA microgels are a good carrier for spatial delivery of cationic proteins for biomedical applications.
", keywords = "Microgel, inverse emulsion, protein delivery, hyaluronic acid, crosslinking.", volume = "12", number = "11", pages = "537-4", }
