长循环pH敏感顺铂脂质体的制备和研究进展
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摘要
背景:顺铂具有很高的抗肿瘤活性,但严重的不良反应限制了其临床应用。脂质体给药系统可通过被动和主动靶向策略,避免其对正常细胞的毒性,增强肿瘤细胞内的药物浓度。目的:综述长循环pH敏感顺铂脂质体的制备及应用研究进展。方法:以"长循环pH敏感顺铂脂质体;纳米载体;肿瘤治疗;生物毒性"或"long-circulating;pH-sensitive liposomes containing cisplatin;nanocarriers;treatment of tumors;biological toxicity"为检索词,检索万方、爱思维尔数据库和Pub Med数据库中关于长循环pH敏感顺铂脂质体的文章。结果与结论:目前多采用冻干再水化法和逆向蒸发法制备长循环pH敏感顺铂脂质体,其中逆向蒸发法已被证明是最适合的方法,因为其制备的脂质体载体粒径小,可形成纯化的长循环pH敏感顺铂脂质体最终产物。长循环pH敏感顺铂脂质体改进了顺铂的药代动力学,减少了其生物毒性,且具有肿瘤细胞局部定位特性。在胰腺肿瘤小鼠模型实验中,长循环pH敏感顺铂脂质体给药系统与以往传统顺铂静脉给药方法相比具有明显优势,表明这种纳米载体给药系统在未来抗肿瘤治疗应用中具有极佳的前景。
BACKGROUND: Although cisplatin is a widely used anticancer agent with a high antitumor activity, its clinical use is limited due to its severe side effects. Liposomes can avoid toxicity to normal cells by using both passive and active targeting strategies, and thus enhance the intracellular concentration of drugs in cancer cells. OBJECTIVE: To review the preparation and application of long-circulating and p H-sensitive liposomes containingcisplatin. METHODS: The authors retrieved the articles about the preparation of long-circulating and p H-sensitive liposomes containing cisplatin in in Wan Fang, Elsevier and Pub Med databases by the keywords as follows: "long-circulating; p H-sensitive liposomes containing cisplatin; nanocarriers; treatment of tumors; biological toxicity" in Chinese and English, respectively. RESULTS AND CONCLUSION: At present, long circulating and p H-sensitive liposomes containing cisplatin are mainly prepared by freeze-thaw and dehydration-rehydration and reverse-phase evaporation. However, reverse-phase evaporation has been proved to be the most suitable method, which can be used to prepare small-size liposome carriers, and the purified long-circulating and p H-sensitive liposome containing cisplatin is finally produced. The long-circulating and p H-sensitive liposome containing cisplatin improves the pharmacokinetics of cisplatin, reduces the biological toxicity, and can localize tumor cells. In the mouse model of pancreatic tumor, this new nano-scaled drug delivery system has obvious advantages compared with the traditional method of cisplatin intravenous administration, which shows a great prospect in the future application of antitumor therapy.
BACKGROUND: Although cisplatin is a widely used anticancer agent with a high antitumor activity, its clinical use is limited due to its severe side effects. Liposomes can avoid toxicity to normal cells by using both passive and active targeting strategies, and thus enhance the intracellular concentration of drugs in cancer cells. OBJECTIVE: To review the preparation and application of long-circulating and p H-sensitive liposomes containingcisplatin. METHODS: The authors retrieved the articles about the preparation of long-circulating and p H-sensitive liposomes containing cisplatin in in Wan Fang, Elsevier and Pub Med databases by the keywords as follows: "long-circulating; p H-sensitive liposomes containing cisplatin; nanocarriers; treatment of tumors; biological toxicity" in Chinese and English, respectively. RESULTS AND CONCLUSION: At present, long circulating and p H-sensitive liposomes containing cisplatin are mainly prepared by freeze-thaw and dehydration-rehydration and reverse-phase evaporation. However, reverse-phase evaporation has been proved to be the most suitable method, which can be used to prepare small-size liposome carriers, and the purified long-circulating and p H-sensitive liposome containing cisplatin is finally produced. The long-circulating and p H-sensitive liposome containing cisplatin improves the pharmacokinetics of cisplatin, reduces the biological toxicity, and can localize tumor cells. In the mouse model of pancreatic tumor, this new nano-scaled drug delivery system has obvious advantages compared with the traditional method of cisplatin intravenous administration, which shows a great prospect in the future application of antitumor therapy.
引文
[1]Zeb A,Qureshi OS,Kim HS,et al.High payload itraconazole-incorporated lipid nanoparticles with modulated release property for oral and parenteral administration.J Pharm Pharmacol.2017;69(8):955-966.
[2]Qureshi OS,Kim HS,Zeb A,et al.Sustained release docetaxelincorporated lipid nanoparticles with improved p Harmacokinetics for oral and parenteral administration.J Microencapsul.2017;34(3):250-261.
[3]Battaglia L,Gallarate M,Peira E,et al.Solid lipid nanoparticles for potential doxorubicin delivery in glioblastoma treatment:preliminary in vitro studies.J Pharm Sci.2014;103(7):2157-2165.
[4]Kakkar D,Dumoga S,Kumar R,et al.PEGylated solid lipid nanoparticles:design,methotrexate loading and biological evaluation in animal models.Med Chem Commun.2015;6(8):1452-1463.
[5]Patel MN,Lakkadwala S,Majrad MS,et al.Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.AAPS Pharm Sci Tech.2014;15(6):1498-1508.
[6]Lee WH,Loo CY,Traini D,et al.Nano-and micro-based inhaled drug delivery systems for targeting alveolar macrop Hages.Expert Opin Drug Deliv.2015;12(6):1009-1026.
[7]Giuberti CDS,Boratto FA,Degobert G,et al.Investigation of alternative organic solvents and methods for the preparation of long-circulating and p H-sensitive liposomes containing cisplatin.J Liposome Res.2013;23(3):220-227.
[8]Leite EA,Souza CM,Carvalho-Júnior AD,et al.Encapsulation of cisplatin in long-circulating and p H-sensitive liposomes improves its antitumor effect and reduces acute toxicity.Int J Nanomedicine.2012;7:5259-5269.
[9]Giuberti CS,Reis ECO,Rocha TGR,et al.Study of the pilot production process of long-circulating and pH-sensitive liposomes containing cisplatin.J Liposome Res.2011;21:60-69.
[10]Biswas S,Kumari P,Lakhani PM,Ghosh B.Recent advances in polymeric micelles for anti-cancer drug delivery.Eur J PHarm Sci.2016;83:184-202.
[11]Gothwal A,Khan I,Gupta U.Polymeric micelles:recent advancements in the delivery of anticancer drugs.Pharm Res.2016;33(1):18-39.
[12]Ng CM,Loh HS,Muthoosamy K,et al.Conjugation of insulin onto the sidewalls of single-walled carbon nanotubes through functionalization and diimide-activated amidation.Int J Nanomedicine.2016;11:1607-1614.
[13]Johnsson M,Edwards K.Liposomes,disks and spH erical micelles:aggregate structure in mixtures of gel pH ase p Hosp Hatidylcholines and poly(ethyleneglycol)-p Hosp Holipids.Biop Hys J.2003;85:3839-3847.
[14]Kasper JC,Friess W.The freezing step in lyopH ilization:pH ysico-chemical fundamentals,freezing methods and consequences on process performance and quality attributes of biop Harmaceuticals.Eur J Pharm Biopharm.2011;78:248-263.
[15]Leite EA,Lana AMQ,Junior ADC,et al.Acute toxicity study of cisplatin loaded long-circulating and p H-sensitive liposomes administered in mice.J Biomed Nanotechnol.2012;8:229-239.
[16]Prabhakar N,Zhang J,Desai D,et al.Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular si RNA delivery.Int J Nanomedicine.2016;11:6591-6608.
[17]Wagner A,Vorauer-Uhl K.Liposome technology for industrial purposes.J Drug Deliv.2011;2011:591325.
[18]Wessman P,Edwards K,Mahlin D.Structural effects caused by sprayand freeze-drying of liposomes and bilayes disks.J PHarm Sci.2010;99:2032-2048.
[19]Desai D,Zhang J,Sandholm J,et al.Lipid bilayer-gated mesoporous silica nanocarriers for tumor-targeted delivery of zoledronic acid in vivo.Mol Pharm.2017;14(9):3218-3227.
[20]Han N,Zhao Q,Wan L,et al.Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance.ACS Appl Mater Interfaces.2015;7(5):3342-3351.
[21]Ganesanab P,Narayanasamya D.Lipid nanoparticles:Different preparation techniques,characterization,hurdles,and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery.Sustain Chem Pharm 2017;6:37-56.
[22]Geszke-Moritz M,Moritz M.Solid lipid nanoparticles as attractive drug vehicles:Composition,properties and therapeutic strategies.Mater Sci Eng C Mater Biol Appl.2016;68:982-994.
[23]Charcosset C,Audrey J,Valour JP,et al.Preparation of liposomes at large scale using the ethanol injection method:Effect of scale-up and injection devices.Chem Eng Res Des.2015;94(2):508-515.
[24]Huang Z,Li X,Zhang T,et al.Progress involving new techniques for liposome preparation.Asian J Pharm Sci.2014;9(4):176-182.
[25]Wagner A,Vorauer-Uhl K,Katinger H.Liposomes produced in a pilot scale:production,purification and efficiency aspects.Eur J Pharm Biopharm.2002;54(2):213-219.
[26]Pham TT,Jaafar-Maalej C,Charcosset C,et al.Liposome and niosome preparation using a membrane contactor for scale-up.Colloids Surf B Biointerfaces.2012;94:15-21.
[27]Silva JO,Fernandes RS,Lopes SCA,et al.p H-Sensitive,Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors:a Feasibility Animal Study.Molecular Imaging Biol.2016;18(6):1-7.
[28]Carlesso FN,Araújo RS,Fuscaldi LL,et al.Preliminary data of the antipancreatic tumor efficacy and toxicity of long-circulating and p H-sensitive liposomes containing cisplatin.Nucl Med Commun.2016;37(7):727-734.
[29]Abuasal BS,Lucas C,Peyton B,et al.Enhancement of intestinal permeability utilizing solid lipid nanoparticles increases[gamma]-tocotrienol oral bioavailability.Lipids.2012;5:461-469.
[30]Andrade ME,Araujo RS,de Barros PA,et al.The role of immunomodulators on intestinal barrier homeostasis in experimental models.Clin Nutr.2015;34:1080-1087.
[31]Araujo JG,Mota L,Leite EA,et al.Biodistribution and antitumoral effect of long-circulating and pH sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice.Exp Biol Med(Maywood).2011;236:808-815.
[32]Arifa RD,Madeira MF,de Paula TP,et al.Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1beta and IL-18 in mice.Am J Pathol.2014;184:2023-2034.
[33]Arivarasu NA,Fatima S,Mahmood R.Effect of cisplatin on brush border membrane enzymes and anti-oxidant system of rat intestine.Life Sci.2007;81:393-398.
[34]Atista MA,Nicoli JR,Martins Fdos S,et al.Pretreatment with citrulline improves gut barrier after intestinal obstruction in mice.JPEN J Parenter Enteral Nutr.2012;36:69-76.
[35]Bearcroft CP,Domizio P,Mourad FH,et al.Cisplatin impairs fluid and electrolyte absorption in rat small intestine:a role for5-hydroxytryptamine.Gut.1999;44:174-179.
[36]Beutheu Youmba S,Belmonte L,Galas L,et al.Methotrexate modulates tight junctions through NF-kappaB,MEK,and JNK pathways.J Pediatr Gastroenterol Nutr.2012;54:463-470.
[37]Beutheu S,Ouelaa W,Guerin C,et al.Glutamine supplementation,but not combined glutamine and arginine supplementation,improves gut barrier function during chemotherapy-induced intestinal mucositis in rats.Clin Nutr.2014;33:694-701.
[38]Bodiga VL,Bodiga S,Surampudi S,et al.Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats.Nutrition.2012;28:572-580.
[39]Carvalho Junior AD,Vieira FP,Melo VJ,et al.Preparation and cytotoxicity of cisplatin-containing liposomes.Braz.J Med Biol Res.2007;40:1149-1157.
[40]de Carvalho Maroni L,de Oliveira Silveira AC,Leite EA,et al.Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and p H-sensitive liposomes against Ehrlich ascitic tumor.Exp Biol Med(Maywood).2012;237:973-984.
[41]Dobrovolskaia MA,Mc Neil SE.Immunological properties of engineered nanomaterials.Nat Nanotechnol.2007;2:469-478.
[42]Elsabahy M,Wooley KL.Cytokines as biomarkers of nanoparticle immunotoxicity.Chem Soc Rev.2013;12:5552-5576.
[43]Ferreira Ddos S,Lopes SC,Franco MS,et al.p H-sensitive liposomes for drug delivery in cancer treatment.Ther.Deliv.2013;4:1099-1123.
[44]Frankenberger M,Haussinger K,Ziegler-Heitbrock L.Liposomal methylprednisolone differentially regulates the expression of TNF and IL-10 in human alveolar macrop Hages.Int Immunop Harmacol.2015;5:289-299.
[45]Araújo RS,Silveira ALM,de Sales E SouzaéL,et al.Intestinal toxicity evaluation of long-circulating and p H-sensitive liposomes loaded with cisplatin.Eur J Pharm Sci.2017;106:142-151.
[46]Monteiro LOF,Fernandes RS,Oda CMR,et al.Paclitaxel-loaded folate-coated long circulating and p H-sensitive liposomes as a potential drug delivery system:A biodistribution study.Biomed Pharmacother.2018;97:489-495.
[47]Gunji S,Obama K,Matsui M,et al.A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microsp Heres incorporating cisplatin.Surgery.2013;154:991-999.
[48]Duan Y,Wei L,Petryk J.Formulation,characterization and tissue distribution of a novel p H-sensitive long-circulating liposome-based theranostic suitable for molecular imaging and drug delivery.Int J Nanomedicine.2016;11:5697-5708.
[49]Leite EA,Giuberti Cdos S,Wainstein AJ,et al.Acute toxicity of long-circulating and p H-sensitive liposomes containing cisplatin in mice after intraperitoneal administration.Life Sci.2009;8(19-20):641-649.
[50]Schillaci O,Corleto VD,Annibale B,et al.Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in gastro-entero pancreatic tumours.Ital J Gastroenterol Hepatol.1999;31 Suppl 2:S186-189.
[51]Li J,Sun K,Ni L,et al.Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity.Toxicol Appl PHarmacol.2012;258:376-383.
[52]Nose S,Wasa M,Tazuke Y,et al.Cisplatin upregulates glutamine transport in human intestinal epithelial cells:the protective mechanism of glutamine on intestinal mucosa after chemotherapy.JPEN J Parenter Enteral Nutr.2010;34:530-537.
[53]Kohli AG,Kieler-Ferguson HM,Chan D,et al.A robust and quantitative method for tracking liposome contents after intravenous administration.J Control Release.2014;176:86-93.
[54]Kohli AG,Kierstead PH,Venditto VJ,et al.Designer lipids for drug delivery:from heads to tails.J Control Release.2014;90:274-287.
[55]Lajunen,T,Kontturi LS,Viitala L,et al.Indocyanine green-loaded liposomes for light-triggered drug release.Mol Pharm.2016;13:2095-2107.
[2]Qureshi OS,Kim HS,Zeb A,et al.Sustained release docetaxelincorporated lipid nanoparticles with improved p Harmacokinetics for oral and parenteral administration.J Microencapsul.2017;34(3):250-261.
[3]Battaglia L,Gallarate M,Peira E,et al.Solid lipid nanoparticles for potential doxorubicin delivery in glioblastoma treatment:preliminary in vitro studies.J Pharm Sci.2014;103(7):2157-2165.
[4]Kakkar D,Dumoga S,Kumar R,et al.PEGylated solid lipid nanoparticles:design,methotrexate loading and biological evaluation in animal models.Med Chem Commun.2015;6(8):1452-1463.
[5]Patel MN,Lakkadwala S,Majrad MS,et al.Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.AAPS Pharm Sci Tech.2014;15(6):1498-1508.
[6]Lee WH,Loo CY,Traini D,et al.Nano-and micro-based inhaled drug delivery systems for targeting alveolar macrop Hages.Expert Opin Drug Deliv.2015;12(6):1009-1026.
[7]Giuberti CDS,Boratto FA,Degobert G,et al.Investigation of alternative organic solvents and methods for the preparation of long-circulating and p H-sensitive liposomes containing cisplatin.J Liposome Res.2013;23(3):220-227.
[8]Leite EA,Souza CM,Carvalho-Júnior AD,et al.Encapsulation of cisplatin in long-circulating and p H-sensitive liposomes improves its antitumor effect and reduces acute toxicity.Int J Nanomedicine.2012;7:5259-5269.
[9]Giuberti CS,Reis ECO,Rocha TGR,et al.Study of the pilot production process of long-circulating and pH-sensitive liposomes containing cisplatin.J Liposome Res.2011;21:60-69.
[10]Biswas S,Kumari P,Lakhani PM,Ghosh B.Recent advances in polymeric micelles for anti-cancer drug delivery.Eur J PHarm Sci.2016;83:184-202.
[11]Gothwal A,Khan I,Gupta U.Polymeric micelles:recent advancements in the delivery of anticancer drugs.Pharm Res.2016;33(1):18-39.
[12]Ng CM,Loh HS,Muthoosamy K,et al.Conjugation of insulin onto the sidewalls of single-walled carbon nanotubes through functionalization and diimide-activated amidation.Int J Nanomedicine.2016;11:1607-1614.
[13]Johnsson M,Edwards K.Liposomes,disks and spH erical micelles:aggregate structure in mixtures of gel pH ase p Hosp Hatidylcholines and poly(ethyleneglycol)-p Hosp Holipids.Biop Hys J.2003;85:3839-3847.
[14]Kasper JC,Friess W.The freezing step in lyopH ilization:pH ysico-chemical fundamentals,freezing methods and consequences on process performance and quality attributes of biop Harmaceuticals.Eur J Pharm Biopharm.2011;78:248-263.
[15]Leite EA,Lana AMQ,Junior ADC,et al.Acute toxicity study of cisplatin loaded long-circulating and p H-sensitive liposomes administered in mice.J Biomed Nanotechnol.2012;8:229-239.
[16]Prabhakar N,Zhang J,Desai D,et al.Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular si RNA delivery.Int J Nanomedicine.2016;11:6591-6608.
[17]Wagner A,Vorauer-Uhl K.Liposome technology for industrial purposes.J Drug Deliv.2011;2011:591325.
[18]Wessman P,Edwards K,Mahlin D.Structural effects caused by sprayand freeze-drying of liposomes and bilayes disks.J PHarm Sci.2010;99:2032-2048.
[19]Desai D,Zhang J,Sandholm J,et al.Lipid bilayer-gated mesoporous silica nanocarriers for tumor-targeted delivery of zoledronic acid in vivo.Mol Pharm.2017;14(9):3218-3227.
[20]Han N,Zhao Q,Wan L,et al.Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance.ACS Appl Mater Interfaces.2015;7(5):3342-3351.
[21]Ganesanab P,Narayanasamya D.Lipid nanoparticles:Different preparation techniques,characterization,hurdles,and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery.Sustain Chem Pharm 2017;6:37-56.
[22]Geszke-Moritz M,Moritz M.Solid lipid nanoparticles as attractive drug vehicles:Composition,properties and therapeutic strategies.Mater Sci Eng C Mater Biol Appl.2016;68:982-994.
[23]Charcosset C,Audrey J,Valour JP,et al.Preparation of liposomes at large scale using the ethanol injection method:Effect of scale-up and injection devices.Chem Eng Res Des.2015;94(2):508-515.
[24]Huang Z,Li X,Zhang T,et al.Progress involving new techniques for liposome preparation.Asian J Pharm Sci.2014;9(4):176-182.
[25]Wagner A,Vorauer-Uhl K,Katinger H.Liposomes produced in a pilot scale:production,purification and efficiency aspects.Eur J Pharm Biopharm.2002;54(2):213-219.
[26]Pham TT,Jaafar-Maalej C,Charcosset C,et al.Liposome and niosome preparation using a membrane contactor for scale-up.Colloids Surf B Biointerfaces.2012;94:15-21.
[27]Silva JO,Fernandes RS,Lopes SCA,et al.p H-Sensitive,Long-Circulating Liposomes as an Alternative Tool to Deliver Doxorubicin into Tumors:a Feasibility Animal Study.Molecular Imaging Biol.2016;18(6):1-7.
[28]Carlesso FN,Araújo RS,Fuscaldi LL,et al.Preliminary data of the antipancreatic tumor efficacy and toxicity of long-circulating and p H-sensitive liposomes containing cisplatin.Nucl Med Commun.2016;37(7):727-734.
[29]Abuasal BS,Lucas C,Peyton B,et al.Enhancement of intestinal permeability utilizing solid lipid nanoparticles increases[gamma]-tocotrienol oral bioavailability.Lipids.2012;5:461-469.
[30]Andrade ME,Araujo RS,de Barros PA,et al.The role of immunomodulators on intestinal barrier homeostasis in experimental models.Clin Nutr.2015;34:1080-1087.
[31]Araujo JG,Mota L,Leite EA,et al.Biodistribution and antitumoral effect of long-circulating and pH sensitive liposomal cisplatin administered in Ehrlich tumor-bearing mice.Exp Biol Med(Maywood).2011;236:808-815.
[32]Arifa RD,Madeira MF,de Paula TP,et al.Inflammasome activation is reactive oxygen species dependent and mediates irinotecan-induced mucositis through IL-1beta and IL-18 in mice.Am J Pathol.2014;184:2023-2034.
[33]Arivarasu NA,Fatima S,Mahmood R.Effect of cisplatin on brush border membrane enzymes and anti-oxidant system of rat intestine.Life Sci.2007;81:393-398.
[34]Atista MA,Nicoli JR,Martins Fdos S,et al.Pretreatment with citrulline improves gut barrier after intestinal obstruction in mice.JPEN J Parenter Enteral Nutr.2012;36:69-76.
[35]Bearcroft CP,Domizio P,Mourad FH,et al.Cisplatin impairs fluid and electrolyte absorption in rat small intestine:a role for5-hydroxytryptamine.Gut.1999;44:174-179.
[36]Beutheu Youmba S,Belmonte L,Galas L,et al.Methotrexate modulates tight junctions through NF-kappaB,MEK,and JNK pathways.J Pediatr Gastroenterol Nutr.2012;54:463-470.
[37]Beutheu S,Ouelaa W,Guerin C,et al.Glutamine supplementation,but not combined glutamine and arginine supplementation,improves gut barrier function during chemotherapy-induced intestinal mucositis in rats.Clin Nutr.2014;33:694-701.
[38]Bodiga VL,Bodiga S,Surampudi S,et al.Effect of vitamin supplementation on cisplatin-induced intestinal epithelial cell apoptosis in Wistar/NIN rats.Nutrition.2012;28:572-580.
[39]Carvalho Junior AD,Vieira FP,Melo VJ,et al.Preparation and cytotoxicity of cisplatin-containing liposomes.Braz.J Med Biol Res.2007;40:1149-1157.
[40]de Carvalho Maroni L,de Oliveira Silveira AC,Leite EA,et al.Antitumor effectiveness and toxicity of cisplatin-loaded long-circulating and p H-sensitive liposomes against Ehrlich ascitic tumor.Exp Biol Med(Maywood).2012;237:973-984.
[41]Dobrovolskaia MA,Mc Neil SE.Immunological properties of engineered nanomaterials.Nat Nanotechnol.2007;2:469-478.
[42]Elsabahy M,Wooley KL.Cytokines as biomarkers of nanoparticle immunotoxicity.Chem Soc Rev.2013;12:5552-5576.
[43]Ferreira Ddos S,Lopes SC,Franco MS,et al.p H-sensitive liposomes for drug delivery in cancer treatment.Ther.Deliv.2013;4:1099-1123.
[44]Frankenberger M,Haussinger K,Ziegler-Heitbrock L.Liposomal methylprednisolone differentially regulates the expression of TNF and IL-10 in human alveolar macrop Hages.Int Immunop Harmacol.2015;5:289-299.
[45]Araújo RS,Silveira ALM,de Sales E SouzaéL,et al.Intestinal toxicity evaluation of long-circulating and p H-sensitive liposomes loaded with cisplatin.Eur J Pharm Sci.2017;106:142-151.
[46]Monteiro LOF,Fernandes RS,Oda CMR,et al.Paclitaxel-loaded folate-coated long circulating and p H-sensitive liposomes as a potential drug delivery system:A biodistribution study.Biomed Pharmacother.2018;97:489-495.
[47]Gunji S,Obama K,Matsui M,et al.A novel drug delivery system of intraperitoneal chemotherapy for peritoneal carcinomatosis using gelatin microsp Heres incorporating cisplatin.Surgery.2013;154:991-999.
[48]Duan Y,Wei L,Petryk J.Formulation,characterization and tissue distribution of a novel p H-sensitive long-circulating liposome-based theranostic suitable for molecular imaging and drug delivery.Int J Nanomedicine.2016;11:5697-5708.
[49]Leite EA,Giuberti Cdos S,Wainstein AJ,et al.Acute toxicity of long-circulating and p H-sensitive liposomes containing cisplatin in mice after intraperitoneal administration.Life Sci.2009;8(19-20):641-649.
[50]Schillaci O,Corleto VD,Annibale B,et al.Single photon emission computed tomography procedure improves accuracy of somatostatin receptor scintigraphy in gastro-entero pancreatic tumours.Ital J Gastroenterol Hepatol.1999;31 Suppl 2:S186-189.
[51]Li J,Sun K,Ni L,et al.Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity.Toxicol Appl PHarmacol.2012;258:376-383.
[52]Nose S,Wasa M,Tazuke Y,et al.Cisplatin upregulates glutamine transport in human intestinal epithelial cells:the protective mechanism of glutamine on intestinal mucosa after chemotherapy.JPEN J Parenter Enteral Nutr.2010;34:530-537.
[53]Kohli AG,Kieler-Ferguson HM,Chan D,et al.A robust and quantitative method for tracking liposome contents after intravenous administration.J Control Release.2014;176:86-93.
[54]Kohli AG,Kierstead PH,Venditto VJ,et al.Designer lipids for drug delivery:from heads to tails.J Control Release.2014;90:274-287.
[55]Lajunen,T,Kontturi LS,Viitala L,et al.Indocyanine green-loaded liposomes for light-triggered drug release.Mol Pharm.2016;13:2095-2107.