Polyethylene glycol (PEG) is extensively used to increasing the in vivo and in vitro stability of liposomes. However, PEGylated liposomes also produce some negative effects with further research, such as low cellular uptake, poor "endosomal escape" of pH sensitive liposome (PSL) and accelerated blood clearance (ABC) phenomenon, and this situation is referred as the "PEG dilemma". "PEG dilemma" posed severe challenges for the targeted delivery of PEGylated liposomes-loaded anticancer drugs, effective intracellular release of PEGylated PSL-encapsulated gene and protein drugs, and repeated administration of PEGylated liposomes. Therefore, it is urgent to solve the "PEG dilemma". This review focused on the definition, classification of "PEG dilemma", and discussed several possible approaches to overcome "PEG dilemma".
Antineoplastic Agents ; chemistry ; Drug Carriers ; chemistry ; Liposomes ; chemistry ; Polyethylene Glycols ; chemistry

OBJECTIVE:To evaluate the inhibitory actions of 3 traditional Chinese drugs on human nasopharyngeal carcinoma cells CNE-2 in vitro.METHODS:The IC50(50% inhibiting concentration)of 3 traditional Chinese drugs on human nasopharyngeal carcinoma cells CNE-2 in vitro was measured by MTT assay.RESULTS:The inhibitory actions of 3 traditional Chinese drugs on human nasopharyngeal carcinoma cells CNE-2 in vitro were enhanced with the increase of the concentration in a concentration-dependent manner,with formulation Ⅲ showing the most potent inhibitory action on CNE-2 cells in vitro.CONCLUSION:The heat-clearing and detoxicating traditional Chinese drugs could markedly inhibit the proliferation of CNE-2 cells.

Aim To observe the expression of migration inhibitory factor (MIF) in the enteric neurons,and to explore the nervous regulation on MIF activity in experimental colitis.Methods Colitis was induced in sensitized rat and mouse by 2,4-dinitrochlorobenzene(DNCB)enema.MIF activity was measured both in the mesentery lymphocyte(by MTT)and in the enteric neurons(by immunofluorescence double staining).6-OHDA was intraperitonealy (ip) administered to mouse before DNCB treatment.Norepinephrine(NE) was added to lymphocyte culture in vitro during MIF preparation.Results The expression of MIF protein in enteric neuron was increased in DNCB-induced colitis in rat.ip 6-OHDA in colitis mouse(38～150 mg?kg-1) resulted in a further increase of MIF activity than ip vehicle in colitis mouse (P

Objective To evaluate the surgical effects and influencing factors of ear malformation.Methods 408 cases were reviewed,including surgical methods and its effect in different condition of malformation,in which autogenous rib cartilage was used in reconstruction of ear.Meanwhile,349 cases(401 ears) double-lobe skin flap and 29 cases(29 ears) retroauricular groove flap were designed according to different condition of malformation.All the patients were treated with canalplasty,and 84 cases(84 ears) with mastoid process of pneumatic type were treated with tympanoplasty and canalplasty.Results months and more follow-up obtained in 335 cases (82%),and 6 months to 5 years follow-up in 273 cases(67%).Surgical effect was satisfactory,the shape of reconstructive ear was verisimilitude,and skull auricle angle was suitability;hearing was improved after operation in 335 ears,especially in 84 ears with canalplasty and tympanoplasty,but hearing was not improved after operation in 45 ears(

Altitude ; Altitude Sickness ; Animals ; Hypoxia ; Iron ; Mice ; Spleen

OBJECTIVE:To study the antipyretic and analgesic effects of Compound tuniuxi sirup.METHODS:Fever was induced by dry yeast in SD rats,then divided the rats into high-dose(33.12g/kg),medium-dose(16.56g/kg),low-dose(8.28g/kg)and control,aspirin group,observed the antipyretic effect;The mice were divided into high-dose(47.84g/kg),medium-dose(23.92g/kg),low-dose(11.96g/kg)and control,aspirin group,then were investigated with hot plate and acetic acid induced body twist.RESULTS:Compound tuniuxi sirup can markedly inhibit the fever in the model anmals 1 hour later,the effect of the high,medium groups are similar to aspirin;and could increase the pain threshold obviously(the low-dose group is obviously in 1.5h～2h(P

Objective To observe the expression of hypoxia inducible faetor-1α (HIF-1α) in the retina of rabbits with acute high intraocular pressure and to investigate the mechanism of systemic domestic recombinant human erythropoietin (rhEPO) protecting the retina from ischemia-reperfusion injury. Methods First, control group and model group were established in rabbit eyes. The acute high intraocular pressure model was established by saline perfusion into anterior chamber, and then hypodermic injection of domestic rhEPO was made. HIF-1α protein in the retina was observed by immunohistochemical staining method on days 1, 3, 7 and 14 after retinal ischemla-reperfusion, respectively. Results No cells with HIF-la positive expression were observed in the retina of the control group. Ceils with HIF-1α positive expression in the model group outnumbered those in the control group (P < 0. 01). The resemblance pattern occurred in EPO group but its degree was slightly greater than that in the model group from day 3 after ischemia-reperfusion (P<0.05). Conclusion Domestic rhEPO can down-regulate the expression of HIF-1α in the retina with acute high intraocular pressure, which may be one of the mechanisms that rhEPO protects the retina from ischemia-reperfusion injury.

Objective:To study the effects of compound preparation of Fanshiliu on lipid metabolism and pancreatic pathological changes in type 2 diabetes mellitus(T2DM)rats with insulin resistance. Methods:After fed with high-calorie food for 8 weeks,the rats received intraperitoneal injection with low dose of streptozotocin(STZ)to induce T2DM animal model,and then the rats were randomly divided into the model group,metformin group,high and low dose group of compound preparation of Fanshiliu. The normal group was given ordinary feed. The rats were sacrified after intragastric administration for six weeks,and fasted for 12 hours after the last administration. The lipid and lipoprotein indices were detected,and pathological morphology of pancreatic tissue was observed. Results:Compared with those in the model group,TC,TG,LDL-C and FFA in each treatment group were reduced,and HDL-C was increased(P < 0. 05). Fanshiliu high dose group and metformin group had obvious hypoglycemic and lipid-lowering effects. The results of pathological morphology of pancreatic tissue under a light microscope showed that the damage was the most obvious in the model group. Compound preparation of Fanshiliu groups and metformin group showed damage in varying degrees. Conclusion:Fanshiliu preparation can effectively adjust blood lipid levels,enhance the insulin sensitivity and reduce damage in pancreas in T2DM rats.

Objective To observe the effects of Xifeng Tongnao capsules on the content of TNF-α and IL-1β in brain tissue of rats with focal cerebral ischemia-reperfusion injury. Methods A total of 120 adult SD rats were randomized into 6 groups: Xifeng Tongnao low-, middle- and high-dose groups, model control group, Buchang Naoxintong group and sham-operated group.Buchang Naoxintong group were treated with Buchang Naoxintong capsules at 0.864 g??kg-1.Xifeng Tongnao high-, middle-and low-dose groups were treated with 3.456, 1.728, and 0.864 g??kg-1 Xifeng Tongnao capsules, respectively;sham-operated group and model control group were treated with equal volume of purified water. Medications were administered intragastrically once daily for 7 days. The acute transient focal cerebral ischemia-reperfusion model was established by middle cerebral artery occlusion ( MCAO) 1 h after the final dose, and rats in the sham-operated group only received anesthesia and stripping without occlusion.All rats were sacrificed after reperfusion for 24 h, and expression levels of TNF-α and IL-1β in the brain tissue were detected by ELISA. Results TNF-αcontent in Xifeng Tongnao capsutes low-, middle-and high-dose groups were (35.34±8.95), (33.75±6.92), and (40.95±5.39) ng??L-1, respectively.IL-1β content were (1.44±0.47), (1.45± 0.23), and (1.61±0.33) ng??L-1 in low-, middle- and high-dose groups, respectively.TNF-α and IL-1β were (38.96±9.84) and (1.56±0.31) ng??L-1, respectively in Buchang Naoxintong group, (52.74±6.76) and (2.79±0.45) ng??L-1in the model control group, and (32.54±4.00) and (1.32±0.22) ng??L-1 in sham-operated group.TNF-αand IL-1βcontent were significantly higher in Buchang Naoxintong group than in sham-operated group ( P<0. 05 ) . TNF-α and IL-1β content were significantly decreased in Xifeng Tongnao high-, middle- and low-dose groups (all P<0.05). Conclusion Xifeng Tongnao capsules can protect brain tissue by supressing TNF-α and IL-1β and alleviating inflammatory injury from ischemia.