| Mini osmotic pumps can continuously delivery drugs or reagents to the target tissues quantitatively at a consistent rate,with a lot of advantages over conventional drug administration methods.Therefore,mini osmotic pumps have been widely used in animal modeling and pharmacological studies.Different types of mini osmotic pumps can provide different load capacities,flow rates and drug releasing periods.It is necessary to select proper types of pumps and to optimize the methods to meet the requirements of different research purposes.Different types of Alzet mini osmotic pumps can continuously delivery chemical compounds from one day up to 6 weeks,depending on the type of pumps.The in vitro test showed that the correct filling and appropriate priming time were critical to achieve the desired drug-releasing rate.The drug-releasing rates of Model 2001D,2001,2002,2004 and 2006 reached 7.7 ± 0.3ul/h,23.6 ± 1.6 ul/d,11.7 ± 0.8 ul/d,5.9 ± 0.4 ul/d and.3.7 ± 0.2 ul/day,respectively,which was comparable to the desired release rate.Prolonging the priming period can improve the performance of mini osmotic pumps.To study the impact of pump implantation on rats,both body weight and food consumption were observed after mini osmotic pump implantation and compared with the oral gavage group.Three days after pump implantation,animals recovered to normal conditions and could be used for experiments.In addition,the drug administration efficiency of mini osmotic pumps was compared with that of mechanical syringe pumps,without significant difference in plasma drug concentration at 3,8 and 24 hrs after drug delivery.Both jugular vein intubation and intrathecal intubation techniques were also optimized.The mini osmotic pumps can be conveniently connected to the surgical animals,and the animals recovered quickly after surgery.The rat formalin acute pain model with clear two-stage pain periods was successfully induced by 5%formalin.Different analgesics were applied to treat the formalin model and the pain behavior was efficiently released with different anti-pain drugs.For example,5 mg/kg morphine could significantly inhibit the pain in phases Ⅰ andⅡ.100 mg/kg gabapentin and 100 mg/kg ibuprofen could significantly inhibit the pain in phases Ⅰ and Ⅱ.Different concentrations of pregabalin could not release the pain in phase I,but 10 mg/kg and 30 mg/kg pregabalin significantly inhibited the pain in phase Ⅱ with t dose dependence.The ProTx-Ⅱ tested in this study is a biotoxin isolated from tarantulas,which can selectively inhibit Nav1.7 sodium channel.Drug stability study data showed that saline was not suitable for dissolving ProTx-Ⅱ which was degraded to 50%in 4 hrs in saline.Tween-80 can maintain ProTx-Ⅱ stability up to 72 hrs,and 0.025%was the lowest concentration for maintaining the stability.ProTx-II delivered by jugular vein infusion could safely increase the plasma drug concentration up to 125 ± 18 nM in rats,with the significantly inhibitory effect against 30%phase II pain behavior in formalin model and delayed of the onset of phase Ⅱ pain.0.1 mg/kg ProTx-Ⅱ delivered by i.v bolus could not release formalin-induced pain at phases I and II.Bypassing brain blood barrier,intrathecal infusion of mini osmotic pumps can deliver ProTx-Ⅱ directly to CNS.Intrathecal infusion of ProTx-Ⅱ at 25 ng/h and 7.5 ng/h could significantly release the pain of formalin model.In conclusion,mini osmotic pumps can be widely used in animal pharmaceutic studies with long-term drug delivery at consistent releasing rate with significant advantages over conventional drug administration methods,including dramatical reduction of labor force,less distress and better welfare for animals. |
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