iPRECIO Micro Infusion Pumps development tool for use in drug discovery 1. Reduced drug requirements 2. Large selection of compatible solvents used in drug discovery 3. Easy to modulate and time exposure profiles with non-optimized compound 4. Easy to use/program 5. Available since 2007 - Solubility issues and need a higher flow rate? - Need more control for dosage due to narrow therapeutic index? - Want to program a drug holiday or maximize efficacy/reduce toxicity with a timed dose during the mornings? - Want to refill with a different test article/drug (sequential administration)? 1

The ability to program the device to start, stop and deliver different doses at different time points or just deliver one continuous dose makes iPRECIO ideally suited to the drug discovery and basic research process. All programmed in an easy to use PC based application software. iPRECIO Micro Infusion Pumps for Drug Delivery Exposure-enabling technology for advancing early preclinical studies and basic research • Enables simple and complex dosing regimens at the click of the mouse/keyboard (ubiquitous PC) – several clicks • Automation which minimizes animal handling • Reduces stress and behavior...

What researchers are saying : Ease of programming: “I was pleasantly surprised with how easy it was to program, fill, and implant the pumps.” Programmable & implantable pump : "This device enables implementation of infusion protocols to reliably and precisely achieve the desired exposure profiles (shapes and timing) with low degree of invasiveness." Improved drug delivery: “The infusion pumps enhanced the delivery of the drug and allowed for us to identify a clean behavioral antidepressant effect, devoid of complications due to daily injections.” Improved drug efficacy: “This study demonstrated...

Introduction > P.1 What Researchers are saying > P.3 Contents > P.4 Research Applications 1-6 > P.5 a b Liver-derived ketone bodies are necessary for food anticipation, Nature Communication Dosing Profile Profoundly Influences Nicotinic Acid's Ability to Improve Metabolic Control in Rats, J. of Lipid Research The abruptness of terminating nicotinic acid delivery has a profound effect on free fatty acid and insulin rebound in rats, 51st EASD Annual Meeting, Stockholm 2015 Ecto-domain phosphorylation promotes functional recovery from spinal cord injury, Scientific Reports Intrathecal administration...

Timed release of Test Article (TA), ßOHB Rohit Chavan, Céline Feillet, Sara S. Fonseca Costa, James E. Delorme, Takashi Okabe, Jürgen A.Ripperger & Urs Albrecht Liver-derived ketone bodies are necessary for food anticipation. Nature Communications 7, Article number: 10580 doi:10.1038/ncomms10580 http://www.nature.com/ncomms/2016/160203/ncomms10580/full/ncomms10580.html?WT.ec_id=NCOMMS-20160205 Figure 1 (Figure 4a in Full Article) Rescue of food anticipation in L Per2-/-mice by ßhydroxybutyrate. (a) Timed release of ßOHB (green) but not NaCl (white) or Na-Pyruvate (purple) in L Per2-/- mice mimics...

iPRECIO SMP-300 pumps were used to test the potential of ßOHB as a FA signal. Short methods or use of the pumps: iPRECIO SMP-300 pumps were programmed to infuse saline vehicle at 2 ul/h, or D-ßOHB at 2 ul/h, or Sodium pyruvate at 5 ul/h, or coconut oil at 5 ul/h prior to meal time (6 h, ZT22ZT4) under Restricted Feeding (RF) Results/significance: Liver-derived ketone bodies are necessary for food anticipation. Timed Release of ßOHB partially rescues FA. Research Need: Timed Release of ßOHB in free moving animal with minimum or no handling to reduce stress and any confounding effects. Additional...

Can different dosing (12 hour rectangular exposure profile) and terminating profile (a slowstep down) of Nicotinic Acid (NiAc) prevent/delay tolerance development and attenuate the FFA rebound development respectively. Tobias Kroon (2016) PhD Thesis, , http://pub.epsilon.slu.se/13324/ http://pub.epsilon.slu.se/13324/1/kroon_t_160429.pdf Thesis and publications cover Drug Discovery implications 1. Importance of time-series disease model 2. Continuous vs. intermittent drug exposures /Programmable, implantable mini-pump 3. Time exposure to physiology/Shape of exposure 4. Meta-analysis/Rank candidates/Predict...

Fig. 3. (Figure 5 in Kroon et al.) Plasma insulin (A, B) and glucose (C, D) concentration in lean (left) and obese (right) following infusion of saline (lean n = 5, obese n = 12) or NiAc (0.17μmol·min -1·kg -1 ) given acutely (NiAc naïve, n = 7/group) or following 5 days continuous (Cont. NiAc, lean n = 4, obese n = 8) or intermittent (Inter. NiAc, lean n = 4, obese n = 9) or 11 days intermittent (Inter. NiAc Day 11, obese n = 4) dosing. The black horizontal bar represents the period of acute NiAc/saline infusion. Data presented as mean ± SE. Figures 2 and 3 licensed material. © <2015> The American...

Intrathecal Administration Continuous infusion of PKA and ATP at 1µl/hour for 14 days where solution in pump was changed every 2 days due to stability of PKA and ATP. Kenji Suehiro, Yuka Nakamura, Shuai Xu, Youichi Uda, Takafumi Matsumura, Yoshiaki Yamaguchi, Hitoshi Okamura, Toshihide Yamashita & Yoshinori Takei Ecto-domain phosphorylation promotes functional recovery from spinal cord injury Scientific Reports 4 , Article number: 4972 (2014) doi:10.1038/srep04972 http://www.nature.com/articles/srep04972 Figure 4 is reproduced from Ecto-domain phosphorylation promotes functional recovery from...

Purpose of the study: Investigate if inhibition of Nogo-66 receptor (NgR) via ecto-domain phosphorylation by protein kinase A (PKA), which blocks activation of the receptor can promote recovery following spinal cord injury. iPRECIO SMP-200 pumps were used to infuse PKA plus ATP for 14 days at 1µl/hour. Solution in reservoir was changed every 2 days. Results/significance: Authors found that infusion of PKA plus ATP into the damaged spinal cord can promote recovery of locomotor function. Research Need: Ability to replace unstable test articles or drugs easily and rapidly without additional surgeries...