PMID- 18342975 OWN - NLM STAT- MEDLINE DCOM- 20080716 LR - 20211020 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 127 IP - 3 DP - 2008 May 8 TI - Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with hydrolytically degradable seals. PG - 280-7 LID - 10.1016/j.jconrel.2008.02.001 [doi] AB - We demonstrate, for the first time, a robust novel polydimethylsiloxane (PDMS) chip that can provide controlled pulsatile release of DNA based molecules, proteins and oligonucleotides without external stimuli or triggers. The PDMS chip with arrays of wells was constructed by replica molding. Poly(lactic acid-co-glycolic acid) (PLGA) polymer films of varying composition and thickness were used as seals to the wells. The composition, molecular weight and thickness of the PLGA films were all parameters used to control the degradation rate of the seals and therefore the release profiles. Degradation of the films followed the PLGA composition order of 50:50 PLGA>75:25 PLGA>85:15 PLGA at all time-points beyond week 1. Scanning electron microscopy images showed that films were initially smooth, became porous and ruptured as the osmotic pressure pushed the degrading PLGA film outwards. Pulsatile release of DNA was controlled by the composition and thickness of the PLGA used to seal the well. Transfection experiments in a model Human Embryonic Kidney 293 (HEK293) cell line showed that plasmid DNA loaded in the wells was functional after pulsatile release in comparison to control plasmid DNA at all time-points. Thicker films degraded faster than thinner films and could be used to fine-tune the release of DNA over day length periods. Finally the PDMS chip was shown to provide repeated sequential release of CpG oligonucleotides and a model antigen, Ovalbumin (OVA), indicating significant potential for this device for vaccinations or applications that require defined complex release patterns of a variety of chemicals, drugs and biomolecules. FAU - Intra, Janjira AU - Intra J AD - Division of Pharmaceutics, College of Pharmacy, University of Iowa, 52242, United States. FAU - Glasgow, Justin M AU - Glasgow JM FAU - Mai, Hoang Q AU - Mai HQ FAU - Salem, Aliasger K AU - Salem AK LA - eng GR - T32 GM007337/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080211 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 0 (CpG ODN 1826) RN - 0 (Dimethylpolysiloxanes) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Silicones) RN - 1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer) RN - 26009-03-0 (Polyglycolic Acid) RN - 33X04XA5AT (Lactic Acid) RN - 63148-62-9 (baysilon) RN - 9006-59-1 (Ovalbumin) RN - 9007-49-2 (DNA) SB - IM MH - Cell Line MH - DNA/administration & dosage/*chemistry MH - Dimethylpolysiloxanes/administration & dosage/*chemistry MH - Humans MH - Hydrolysis MH - Lactic Acid/administration & dosage/*chemistry MH - Oligodeoxyribonucleotides MH - Ovalbumin/administration & dosage/*chemistry MH - Plasmids/genetics MH - Polyglycolic Acid/administration & dosage/*chemistry MH - Polylactic Acid-Polyglycolic Acid Copolymer MH - Silicones/administration & dosage/*chemistry MH - Transfection EDAT- 2008/03/18 09:00 MHDA- 2008/07/17 09:00 CRDT- 2008/03/18 09:00 PHST- 2007/12/06 00:00 [received] PHST- 2008/01/28 00:00 [revised] PHST- 2008/02/04 00:00 [accepted] PHST- 2008/03/18 09:00 [pubmed] PHST- 2008/07/17 09:00 [medline] PHST- 2008/03/18 09:00 [entrez] AID - S0168-3659(08)00076-X [pii] AID - 10.1016/j.jconrel.2008.02.001 [doi] PST - ppublish SO - J Control Release. 2008 May 8;127(3):280-7. doi: 10.1016/j.jconrel.2008.02.001. Epub 2008 Feb 11.