Polymer particle-based micromolding to fabricate novel microstructures

Conventional micromolding provides rapid and low-cost methods to fabricate polymer microstructures, but has limitations when producing sophisticated designs. To provide more versatile micromolding techniques, we developed methods based on filling micromolds with polymer microparticles, as opposed to polymer melts, to produce microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions. Polymer microparticles of 1 to 30 μm in size were made from PLA, PGA and PLGA using established spray drying and emulsion techniques either with or without encapsulating model drug compounds. These polymer microparticles were filled into PDMS micromolds at room temperature and melted or bonded together to form microstructures according to different protocols. Porous microstructures were fabricated by ultrasonically welding microparticles together in the mold while maintaining the voids inherent in their packing structure. Multi-layered microstructures were fabricated to have different compositions of polymers and encapsulated compounds located in different regions of the microstructures. More complex arrowhead microstructures were fabricated in a two-step process using a single mold. To assess possible applications, microstructures were designed as microneedles for minimally invasive drug delivery. Multi-layer microneedles were shown to insert into cadaver tissue and, according to design, detach from their base substrate and remain embedded in the tissue for controlled release drug delivery over time. We conclude that polymer particle-based micromolding can encapsulate compounds within microstructures composed of multiple materials, having complex geometries, and made using mild processing conditions.

[1]  Dong-Chul Han,et al.  PDMS-based micro PCR chip with Parylene coating , 2003 .

[2]  L. Brannon-Peppas,et al.  Microparticle Drug Delivery Systems , 2004 .

[3]  D. Armani,et al.  Microfabrication technology for polycaprolactone, a biodegradable polymer , 2000 .

[4]  Bharat Bhushan,et al.  Adhesion and friction properties of polymers in microfluidic devices , 2005 .

[5]  Steve Arscott,et al.  Integrated microfluidics based on multi-layered SU-8 for mass spectrometry analysis , 2004 .

[6]  Jin-Woo Choi,et al.  Disposable smart lab on a chip for point-of-care clinical diagnostics , 2004, Proceedings of the IEEE.

[7]  L. Draghi,et al.  Microspheres leaching for scaffold porosity control , 2005, Journal of materials science. Materials in medicine.

[8]  J. Benoit,et al.  Biodegradable microspheres: Advances in production technology , 1996 .

[9]  David J. Odde,et al.  Micro-Patterning of Animal Cells on PDMS Substrates in the Presence of Serum without Use of Adhesion Inhibitors , 2004, Biomedical microdevices.

[10]  Rebecca S. Shawgo,et al.  Biocompatibility and biofouling of MEMS drug delivery devices. , 2003, Biomaterials.

[11]  James Prescott,et al.  On powder flowability , 2000 .

[12]  Harish Manohara,et al.  Polydimethylsiloxane ( PDMS ) for High Aspect Ratio Three-dimensional MEMS , 2001 .

[13]  J. Park,et al.  Double-walled microparticles for single shot vaccine , 1997 .

[14]  J. Humphrey,et al.  Cancer Drug Discovery and Development , 2003 .

[15]  Sung-chul Shin,et al.  Magnetic enhancement of iron oxide nanoparticles encapsulated with poly(d,l-latide-co-glycolide) , 2005 .

[16]  Robert Langer,et al.  In vivo release from a drug delivery MEMS device. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[17]  Mark G. Allen,et al.  Integrated vertical screen microfilter system using inclined SU-8 structures , 2003, The Sixteenth Annual International Conference on Micro Electro Mechanical Systems, 2003. MEMS-03 Kyoto. IEEE.

[18]  W. Friess,et al.  Collagen/PLGA microparticle composites for local controlled delivery of gentamicin. , 2003, Journal of pharmaceutical sciences.

[19]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[20]  S C Jakeway,et al.  Miniaturized total analysis systems for biological analysis , 2000, Fresenius' journal of analytical chemistry.

[21]  Jeung Sang Go,et al.  In-channel 3-D micromesh structures using maskless multi-angle exposures and their microfilter application , 2004 .

[22]  Bernhard E. Boser,et al.  An Immunoassay Platform Based on CMOS Hall Sensors , 2002 .

[23]  Mark G. Allen,et al.  Polymer Microneedles for Controlled-Release Drug Delivery , 2006, Pharmaceutical Research.

[24]  Daniel G. Anderson,et al.  Poly-beta amino ester-containing microparticles enhance the activity of nonviral genetic vaccines. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[25]  A. Shahzamani,et al.  In vivo characterization of sustained-release formulations of human growth hormone. , 1997, The Journal of pharmacology and experimental therapeutics.

[26]  D. K. Majumdar,et al.  Eudragit S100 entrapped insulin microspheres for oral delivery , 2005, AAPS PharmSciTech.

[27]  M. Allen,et al.  Microfabricated microneedles for gene and drug delivery. , 2000, Annual review of biomedical engineering.

[28]  Hong-Seok Noha,et al.  Parylene micromolding, a rapid and low-cost fabrication method for parylene microchannel , 2004 .

[29]  Jung-Hwan Park,et al.  Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[30]  A. Ahluwalia,et al.  Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. , 2003, Biomaterials.

[31]  Mark R Prausnitz,et al.  Microneedles for transdermal drug delivery. , 2004, Advanced drug delivery reviews.

[32]  Joon B. Park Biomaterials:An Introduction , 1992 .

[33]  M. Vert,et al.  Something new in the field of PLA/GA bioresorbable polymers? , 1998, Journal of controlled release : official journal of the Controlled Release Society.