Novel PLGA Microspheres for Sustained Delivery of Antisense Oligonucleotide

doi:10.1007/s40242-013-3127-2

Abstract

Abstract:

Novel poly(lactide-co-glycolide acid)(PLGA) microspheres were developed for sustained delivery of antisense oligonucleotide(ASO). First, a new cationic agent, polyethylenimine(PEI) conjugated to linoleic acid(LA)(PEI-LA) was synthesized by reacting PEI(M_w=800) with linoleoyl chloride. Then, PEI-LA was combined with LOR-2501 to form electrostatic complexes at moderate nitrogen-to-phosphate(N/P) molar ratios which were then encapsulated into poly(lactide-co-glycolide) microspheres by a multiple emulsion-solvent evaporation technique. With an increase in ASO/PEI-LA concentration from 5% to 10%, encapsulation efficiency of ASO in the microspheres reduced from 72.14% to 57.62%, and the particle size of microspheres increased from 28.58 μm to 34.76 μm. In vitro studies show that the release profile of ASO from microspheres prepared at 7.5% ASO-PEI-LA lasted for 14 d. The novel microspheres have a potential use as a sustained release vehicle for ASO.

Key words: Drug delivery, PLGA microsphere, Polyethylenimine, Antisense oligonucleotide

XIE Jing, LI Xin, JIANG Chao-jun, LEE Robert Jian-guang, ZHOU Yu-lin, TENG Le-sheng. Novel PLGA Microspheres for Sustained Delivery of Antisense Oligonucleotide[J]. Chemical Research in Chinese Universities, 2013, 29(5): 1003-1005.

References

[1] Crooke S. T., Bennett C. F., Annu Rev. Pharmacol., 1996, 36(1), 107
[2] Kole R., Krainer A. R., Altman S., Nat. Rev. Drug Discov., 2012, 11(2), 125
[3] Zhao X. B., Pan F., Holt C. M., Lewis A. L., Lu J. R., Expert Opin. Drug Del., 2009, 6(7), 673
[4] Ciardiello F., Bianco R., Damiano V., Fontanini G., Pomatico G., de Placido S., Bianco A. R., Mendelsohn J., Tortora G., Clin. Cancer Res., 2000, 6(9), 3739
[5] Hu Y. P., Cherton-Horvat G., Dragowska V., Baird S., Korneluk R. G., Durkin J. P., Mayer L. D., La Casse E. C., Clin. Cancer Res., 2003, 9(7), 2826
[6] Olie R. A., Simoes-Wust A. P., Baumann B.,Leech S. H., Fabbro D., Stahel R. A., Zangemeister-Wittke U., Cancer Res., 2000, 60(11), 2805
[7] Aichberger K. J., Mayerhofer M., Krauth M. T., Skvara H., Florian S., Sonneck K., Akgul C., Derdak S., Pickl W. F., Wacheck V., Selzer E., Monia B. P., Moriggl R., Valent P., Sillaber C., Blood, 2005, 105(8), 3303
[8] Marcucci G., Byrd J. C., Dai G. W., Klisovic M. I., Kourlas P. J., Young D. C., Cataland S. R., Fisher D. B., Lucas D., Chan K. K., Porcu P., Lin Z. P., Farag S. F., Frankel S. R., Zvviebel J. A., Kraut E. H., Balcerzak S. P.,. Bloomfield C. D., Grever M. R., Caligiuri M. A., Blood, 2003, 101(2), 425
[9] Olie R. A., Hafner C., Kuttel R., Sigrist B., Willers J., Dummer R., Hall J., Stahel R. A., Zangemeister-Wittke U., J. Invest. Dermatol., 2002, 118(3), 505
[10] Stevenson J. P., Yao K. S., Gallagher M., Friedland D., Mitchell E. P., Cassella A., Monia B., Kwoh T. J., Yu R., Holmlund J., Dorr F. A., O'Dwyer P. J., J. Clin. Oncol., 1999, 17(7), 2227
[11] Waters J. S., Webb A., Cunningham D., di Stefano F., Cotter F. E., J. Clin. Oncol., 2000, 18(9), 1812
[12] Agrawal S., Trends Biotechnol., 1996, 14(10), 376
[13] Levin A. A., Biochimica et Biophysica Acta, Gene Structure and Expression, 1999, 1489(1), 69
[14] Xu P. W, Zhang H., Hu H., Xu W. B., Zhang H. P., Hu H. B., Hu J. C., Zhou L. L., Chinese J. Chem., 2012, 30(2), 445
[15] Fa H. B., Zhang J., Qi H., Yin W., Zhang H. F., Hou C. J., Huo D. Q., Lu W. J., Chem. J. Chinese Universities, 2013, 34(5), 1160
[16] de Rosa G., Quaglia F., Bochot A., Ungaro F., Fattal E., Biomacromolecules, 2003, 4(3), 529
[17] de Rosa G., Quaglia F., la Rotonda M. I., Appel M., Alphandary H., Fattal E., J. Pharm. Sci, US, 2002, 91(3), 790
[18] de Rosa G., Bochot A., Quaglia F., Besnard M., Fattal E., Int J. Pharm, 2003, 254(1), 89
[19] Dos Santos A. L. G., Bochot A., Doyle A., Tsapis N., Siepmann F., Schmaler J., Besnard M., Behar-Cohen F., Fattal E., J. Control Release, 2006, 112(3), 369
[20] Howard K. A., Li X. W., Somavarapu S., Singh J., Green N., Atuah K. N., Ozsoy Y., Seymour L. W., Alpar H. O., BBA: Gen Subjects , 2004, 1674(2), 149