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Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.
ABSTRACT
Objective To investigate the antioxidative effects of all-trans retinoic acid (ATRA) on the intestinal ischemia reperfusion.Methods Thirty-two male SD rats were randomly divided into the sham operation group,occlusion group,dimethyl sulfoxide (DMSO) group and the ATRA group according to the random number table.There were 8 rats in each group.Rat models of intestinal ischemia reperfusion were established by clamping the superior mesenteric arteries for 60 minutes,and then restore the blood flow for 120 minutes.Superior mesenteric arteries were only separated without clamping in the sham operation group.Rats in the ATRA group received ATRA pretreatment through intragastric infusion at the dosage of 15 μg/g for 5 days,and then ATRA pretreatment at 6 hours before operation.Rats in the DMSO group received intragastric infusion of DMSO at the same dosage.The concentration of ATRA at 5 hours before operation was detected by high performance liquid chromatography.The pathomorphological changes of the ileal mucosa were detected by hematoxylin-eosin staining,and the Chiu's scores on the ileal mucosa were evaluated.The serum content of diamine oxidase (DAO),tissue level of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) were detected by colorimetry.Protein expression of manganese superoxide dismutase (MnSOD) in the ileal tissues was detected by Western blot.All data were analyzed using the analysis of variance or LSD-t test.Results The concentrations of ATRA in the ATRA group was (827 ±276) μg/L,which was significantly higher than (48 ± 12) μg/L of the sham operation group,(55 ± 15) μg/L of the occlusion group and (63 ± 20) μg/L of the DMSO group (t =11.242,11.138,11.013,P ＜ 0.05).The morphology of the ileal mucosa was normal in the sham operation group,while the ileal mucosa was severely damaged in the occlusion group and the DMSO group.The injury of the ileal mucosa in the ATRA group was slight.The Chiu's scores of the occlusion group,DMSO group and the ATRA group were 3.83 ±0.77,3.92 ± 0.87 and 2.42 ± 0.75,which were significantly higher than 0.37 ± 0.28 of the sham operation group (t =9.803,10.040,5.793,P ＜0.05).The Chiu's scores of the ATRA group was significantly lower than that of the occlusion group and the DMSO group (t =4.009,4.247,P ＜ 0.05).The DAO levels of the occlusion group,DMSO group and the ATRA group were (26.3 ±4.4)U/L,(25.1 ± 4.3)U/L and (20.8 ±3.8)U/L,which were significantly higher than (14.2 ± 1.9) U/L of the sham operation group (t =6.493,5.835,3.534,P ＜ 0.05).The level of DAO of the ATRA group was significantly lower than that of the occlusion group and the DMSO group (t =2.959,2.301,P ＜0.05).The levels of MDA of the occlusion group,DMSO group and the ATRA group were (16.9 ± 4.0) μmol/g,(16.0 ± 3.5) μmol/g and (11.3 ± 3.1) μmol/g,which were significantly higher than (5.4 ± 1.0) μmol/g of the sham operation group (t =7.397,6.821,3.821,P ＜ 0.05).The level of MDA of the ATRA group was signifcantly lower than that of the occlusion group and the DMSO group (t =3.575,3.000,P ＜ 0.05).The SOD activity of the occlusion group,DMSO group and the ATRA group were (108 ±22) U/mg,(98 ± 19) U/mg and (181 ± 38)U/mg,which were significantly lower than (243 ± 37)U/mg of the sham operation group (t =8.939,9.647,4.106,P ＜ 0.05).The SOD activity of the ATRA group was significantly higher than that of the occlusion group and the DMSO group (t =4.833,5.541,P ＜ 0.05).The relative protein expressions of the MnSOD of the occlusion group and the DMSO group were 0.36 ± 0.08 and 0.28 ± 0.07,which were significantly lower than 0.93 ± 0.13 of the sham operation group (t =8.972,10.101,P ＜ 0.05).The relative protein expression of the MnSOD of the ATRA group was 0.80 ± 0.19,which was significantly higher than that of the occlusion group and the DMSO group (t =6.948,8.077,P ＜ 0.05),while it was not significantly different from that of the sham operation group (t =2.024,P ＞ 0.05).Conclusion Through up-regulating the expression of MnSOD and improving the antioxidative capacity of tissue,ATRA pretreatment can attenuate intestinal ischemia and reperfusion injury.
ABSTRACT
Objective To investigate the effects of minimal-flow sevoflurane anesthesia combined with a new CO2 adsorbent Amsorb Plus calcium lime on the hepatic and renal functions in patients.Methods Seventytow ASA Ⅰ or Ⅱ patients,aged 20-60 yr,scheduled for gastrointestinal surgery under general anesthesia,were randomized into 2 groups (n =36 each):middle-flow anesthesia group (group G1 ) and minimal-flow anesthesia group (group G2 ).Amsorb Plus calcium lime was added into the CO2 absorption canister and the core temperature of the calcium lime was continuously monitored and recorded.The patients were tracheal intubated after anesthesia induction and mechanically ventilated.The initial sevoflurane concentration was set at 4％ and the fresh gas flow of oxygen was set at 4 L/min.After the end-tidal concentration of sevoflurane reached 2.6％,the fresh gas flow of oxygen was adjusted to 2 L/min in group G1 or 0.5 L/min in group G2.The end-tidal concentration of sevoflurane was maintained at 2.4％-2.8％ during operation.Venous blood samples were taken 24 h before and 24 h after operation for determination of the serum concentrations of total bilirubin (TBIL),direct bilirubin (DBIL),blood urea nitrogen (BUN) and creatinire (Cr) and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST).Urine samples were obtained at 24 h before and after operation to detect the concentration of glucose and protein.The urine glucose and protein positive patients were recorded.Results There was no significant difference in the core temperature of calcium lime at different time points between the two groups ( P ＞ 0.05 ).Compared with that at 24 h before operation,AST activity,TBIL and DBIL concentrations were significantly increased,BUN concentration was significantly decreased,but no significant change was found in the Cr concentration and the number of urine glucose and protein positive patients at 24 h after operation in group G1,and DBIL concentration was significantly increased,while BUN concentration was significantly decreased at 24 h after operation in group G2 ( P ＜ 0.05 ).There was no significant difference in the parameters of hepatic and renal functions between the two groups ( P ＞ 0.05).Conclusion The combination of minimal-flow sevoflurane anesthesia and Amsorb Plus calcium lime exerts no effect on the hepatic and renal functions,the effect is similar to that of middle-flow anesthesia,and it can be safely used in patients.