Abstract
An implantable manually-actuated drug delivery device, consisting of a refillable drug reservoir, flexible cannula, check valve, and suture tabs, was investigated as a new approach for delivering pharmaceuticals to treat chronic ocular diseases. Devices are fabricated by molding and bonding three structured layers of polydimethylsiloxane. A 30 gauge non-coring needle was used to refill the reservoir; this size maximized the number of repeated refills while minimizing damage to the reservoir. The check valve cracking pressure was 76 ± 8.5 mmHg (mean ± SE, n = 4); the valve sustained > 2000 mmHg of reverse pressure without leakage. Constant delivery at 1.57 ± 0.2 µL/sec and 0.61 ± 0.2 µL/sec (mean ± SE, n = 4) under 500 mmHg and 250 mmHg of applied pressure, respectively, was obtained in benchtop experiments. The valve closing time constant was 10.2 s for 500 mmHg and 14.2 s for 250 mmHg. Assembled devices were successfully demonstrated in benchtop, ex vivo, and in vivo experiments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
J. Ambati, E.S. Gragoudas, J.W. Miller, T.T. You, K. Miyamoto, F.C. Delori, A.P. Adamis, Invest. Ophthalmol. Vis. Sci. 41, 5 (2000)
L. Cao, S. Mantell, D. Polla, Sens. Actuators A Phys 94, 1–2 (2001). doi:10.1016/S0924-4247(01)00680-X
A.K. Dash, G.C. Cudworth 2nd, J. Pharmacol. Toxicol. Methods 40, 1 (1998). doi:10.1016/S1056-8719(98)00027-6
D.C. Duffy, J.C. McDonald, O.J.A. Schueller, G.M. Whitesides, Anal. Chem. 70, 23 (1998). doi:10.1021/ac980656z
F.T. Fraunfelder, JAMA 237, 5 (1977). doi:10.1001/jama.237.5.446b
F.T. Fraunfelder, Ophthalmology 86, 1 (1979)
F.T. Fraunfelder, Ophthalmology 87, 2 (1980)
F.T. Fraunfelder, J. Am. Ophthalmol 110, 4 (1990)
F.T. Fraunfelder, S.M. Meyer, J. Aust. Ophthalmol 12, 2 (1984)
F.W. Fraunfelder, Insight 29, 2 (2004)
F.W. Fraunfelder, F.T. Fraunfelder, Ophthalmology 111, 7 (2004)
D.H. Geroski, H.F. Edelhauser, Invest. Ophthalmol. Vis. Sci. 41, 5 (2000)
A.C.R. Grayson, R.S. Shawgo, Y.W. Li, M.J. Cima, Adv. Drug Deliv. Rev. 56, 2 (2004)
J.Z. Hilt, N.A. Peppas, Int. J. Pharm 306, 1–2 (2005). doi:10.1016/j.ijpharm.2005.09.022
H. Jayaram, I. Calder, Anaesth. Intensive Care Med. 5, 9 (2004). doi:10.1383/anes.5.9.300.49895
S.S. Lee, P. Yuan, M.R. Robinson, Encyclopedia of Biomaterials and Biomedical Engineering, (2004)
R. Lo, K. Kuwahara, P.Y. Li, R. Agrawal, M.S. Humayun, E. Meng, (Okinawa, Japan, 2006), pp. 4
R. Lo, P.Y. Li, S. Saati, R. Agrawal, M.S. Humayun, E. Meng, Lab Chip 8, 7 (2008)
N. Mamalis, L. Kearsley, E. Brinton, Curr. Opin. Ophthalmol. 13, 1 (2002). doi:10.1097/00055735-200202000-00004
J.C. McDonald, D.C. Duffy, J.R. Anderson, D.T. Chiu, H.K. Wu, O.J.A. Schueller, G.M. Whitesides, Electrophoresis 21, 1 (2000). doi:10.1002/(SICI)1522-2683(20000101)21:1<27::AID-ELPS27>3.0.CO;2-C
J.C. McDonald, G.M. Whitesides, Acc. Chem. Res. 35, 7 (2002). doi:10.1021/ar010110q
D.C. Metrikin, R. Anand, Curr. Opin. Ophthalmol. 5, 3 (1994). doi:10.1097/00055735-199406000-00005
S.Z. Razzacki, P.K. Thwar, M. Yang, V.M. Ugaz, M.A. Burns, Adv. Drug Deliv. Rev. 56, 2 (2004)
R. Ritch, M.B. Shields, T. Krupin, The Glaucomas (Mosby, St. Louis, 1989)
J.T. Santini, M.J. Cima, R. Langer, Nature 397, 6717 (1999)
D. Smerdon, Curr. Anaesth. Crit. Care 11, 6 (2000). doi:10.1054/cacc.2000.0296
M.A. Unger, H.P. Chou, T. Thorsen, A. Scherer, S.R. Quake, Science 288, 5463 (2000). doi:10.1126/science.288.5463.113
J.T. Wilensky, Curr. Opin. Ophthalmol. 10, 2 (1999). doi:10.1097/00055735-199904000-00005
H.K. Wu, B. Huang, R.N. Zare, Lab Chip 5, 12 (2005). doi:10.1039/b418042a
B. Ziaie, A. Baldi, M. Lei, Y. Gu, R.A. Siegel, Adv. Drug Deliv. Rev. 56, 2 (2004). doi:10.1016/j.addr.2003.09.001
Acknowledgments
This work was funded in part by the Engineering Research Centers Program of the NSF (EEC-0310723), NIH (1R21EY018490-01), NIH core grant (EY03040), an unrestricted grant by Research to Prevent Blindness, and Bausch and Lomb. The authors would like to thank Mr. Trevor Roper and Mr. Merrill Roragen for fabrication assistance, Dr. Yu-Chong Tai for providing access to the Caltech Micromachining Laboratory Cleanroom, Ms. Lilian Tran for conducting PDMS bonding experiments, Mr. Kenrick Kuwahara for his contributions to optimizing the assembly of the drug delivery device, Mr. Tun Min Soe for artistic illustrations of the device in the eye, and Ms. Mei Li Nickles for creating the SolidWorks images of the test jigs.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lo, R., Li, PY., Saati, S. et al. A passive MEMS drug delivery pump for treatment of ocular diseases. Biomed Microdevices 11, 959 (2009). https://doi.org/10.1007/s10544-009-9313-9
Published:
DOI: https://doi.org/10.1007/s10544-009-9313-9