The different fate of liposomes among species has been discovered and mentioned in many studies, but the underlying mechanisms have not been explored. In the present work, we concentrated on the in vivo fate of PEGylated liposomes (sLip) in three commonly used species (mice, rats, and dogs). It was exhibited that the accelerated blood clearance (ABC) phenomenon and hypersensitivity in large animals (beagle dogs) were much more significant than that in rodents. We demonstrated that anti-PEG IgM (partially) and complement (mostly) determined the elimination of sLip and linked the distinct interspecies performances with the diverse complement capacity among species. Based on the data from animals and clinical patients, it was revealed that the fate of sLip in large animals was closer to that in humans, for the sufficient complement capacity could expose the potential adverse reactions caused by anti-PEG antibodies. Our results suggested that the distinctive interspecies performances of sLip were highly related to the physiological variabilities among species, which should not be overlooked in the innovation and translation of nanomedicines.

[Objective]To investigate the changes of the hemodynamics and pulmonary histopathology in acute spinal cord injured rats during isoflurane inhalation.[Method]Sixty male SD rats with body weights of 300～330 g were divided into 3 groups:chloral hydrate group,1.5% isoflurane group and 3% isoflurane group.Epidural balloon compression of the T8 spinal cord was performed.Blood pressure and heart rate were monitored during surgery.All animals were sacrificed 10 min after being compressed.The author harvested the lung and recorded lung wet/dry weight ratios(W/D)to assess lung injury severity,and observed the changes of the pulmonary pathology.[Result]Blood pressure in all animals was higher than that of the baseline during the spinal cord injury,but the heart rate was lower than that of the baseline(P0.05).Rats from the 1.5% isoflurane group exhibited severe neurogenic pulmonary edema.The W/D in 1.5% group was significantly higher than those in the other two groups(P

[Objective]To investigate the relationship between neurogenic pulmonary edema(NPE)and the changes of substance P in serum and bronchoatveolar lavage fluid(BALF)in acute spinal cord injured rats during isoflurane inhalation.[Method]Thirty male SD rats with body weight of 300-330g were randomly divided into 3 groups:1.5% isoflurane group,chloral hydrate group and sham operation group,ten in each group.Epidural balloon compression of the T8 spinal cord was performed.Alt animals were sacrificed 10 min after being compressed.The content of substance P and protein concentration in serum and BALF were measured.Then the lung permeability index(LPI)was calculated.[Result]The content of substance P in serum and BALF in 1.5% isofiurane group was higher than that in chloral hydrate group(P0.05).[Conclusion]1.5% isofturane can stimulate the release of substance P to take part in the development of neurogenic pulmonary edema in rats.

BACKGROUND: Bupivacaine is widely used to alleviate post-operation pain and cure acute and chronic pain caused by inflammation or cancer.Its analgesic time cannot meet the request that drug is released slowly to prolong the analgesic time in clinic.OBJECTIVE: To detect the alleviating effect of bupivacaine polylactic acid microspheres taking high molecular polymer-polylactic acid as vector in rabbits with high performance liquid chromatograph (HPLC) and traditional skin test method.DESIGN: A completely randomized controlled animal experimental study.SETTING: School of Pharmacy, Second Military Medical University of Chinese PLAMATERIALS: Sixteen New Zealand rabbits, weighing (2.58±0.17)kg were used in this experiment.INTERVENTIONS: The experiment was carried out at the Department of pharmaceutics, School of Pharmacy, Second Military Medical University of Chinese PLA between September and November 2002. ① Animal models were established according to traditional skin test method. ② Totally 16 New Zealand rabbits were randomly divided into 2 groups: Group A and Group B, with 8 in each one. 5 mg/kg bupivacaine parenteral solution was injected subcutaneously in Group A, 5 mg/kg bupivacaine polylactic acid microspheres were implanted between subcutaneous tissue and sarcolemma in Group B. We took 1.5 mL blood from ear border vein at 5, 10, 20, 30,45 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after administration of bupivacaine parenteral solution respectively in Group A and another 1.5 mL at 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 3 6, 48 and 60 hours after admistration of bupivacaine microsphere powder for index detection. ③ HPLC method was used to detect the concentration and releasing effect of bupivacaine in blood serum.MAIN OUTCOME MEASURES: Concentration change of bupivacaine in blood serum and efficacy diameter of local anesthetic.RESULTS:All the 16 rabbits entered the stage of result analysis. ①Change of bupivacaine concentration: Plasma bupivacaine concentration in Group A reached the peaked quickly after subutaneous injection with the high concentration of 2.466 4 mg/L, then declined quickly. Plasma bupivacaine concentration in Group B was relative stable, reached a peak much slowly after subcutaneous implantation, with peak concentration of 0.778 1 mg/L, and the plasma bupivacaine concentration maintained a relative low level, the mean retention time was obviously prolonged (P ＜ 0.05).② Alleviating effect of bupivacaine: The analgesic time was significantly longer in the bupivacaine microsphere group than in the bupivacaine parenteral solution group (P ＜ 0.05).CONCLUSION:Bupivacaine polylactic acid microspheres have sustained release effects in rabbits.