The Effect of PEGylation on Drugs' Pharmacokinetic Parameters; from Absorption to Excretion.

Ali Khajeei, Salar Masoomzadeh, Tooba Gholikhani, Yousef Javadzadeh
Author Information
  1. Ali Khajeei: Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. ORCID
  2. Salar Masoomzadeh: Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. ORCID
  3. Tooba Gholikhani: Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. ORCID
  4. Yousef Javadzadeh: Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. ORCID

Abstract

Until the drugs enter humans life, they may face problems in transportation, drug delivery, and metabolism. These problems can cause reducing drug's therapeutic effect and even increase its side effects. Together, these cases can reduce the patient's compliance with the treatment and complicate the treatment process. Much work has been done to solve or at least reduce these problems. For example, using different forms of a single drug molecule (like Citalopram and Escitalopram); slight changes in the drug's molecule like Meperidine and α-Prodine, and using carriers (like Tigerase®). PEGylation is a recently presented method that can use for many targets. Poly Ethylene Glycol or PEG is a polymer that can attach to drugs by using different methods and resulting sustained release, controlled metabolism, targeted delivery, and other cases. Although they will not necessarily lead to an increase in the effect of the drug, they will lead to the improvement of the treatment process in certain ways. In this article, the team of authors has tried to collect and carefully review the best cases based on the PEGylation of drugs that can help the readers of this article.

Keywords

References

D’souza A.A.; Shegokar R.; Polyethylene glycol (PEG): A versatile polymer for pharmaceutical applications. Expert Opin Drug Deliv 2016,13(9),1257-1275 [DOI: 10.1080/17425247.2016.1182485]
Abuchowski A.; van Es T.; Palczuk N.C.; Davis F.F.; Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem 1977,252(11),3578-3581 [DOI: 10.1016/S0021-9258(17)40291-2]
Yamaoka T.; Tabata Y.; Ikada Y.; Distribution and tissue uptake of poly(ethylene glycol) with different molecular weights after intravenous administration to mice. J Pharm Sci 1994,83(4),601-606 [DOI: 10.1002/jps.2600830432]
Monfardini C.; Schiavon O.; Caliceti P.; Morpurgo M.; Harris J.M.; Veronese F.M.; A branched monomethoxypoly(ethylene glycol) for protein modification. Bioconjug Chem 1995,6(1),62-69 [DOI: 10.1021/bc00031a006]
Harris J.M.; Chess R.B.; Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov 2003,2(3),214-221 [DOI: 10.1038/nrd1033]
Israelachvili J.; The different faces of poly(ethylene glycol). Proc Natl Acad Sci USA 1997,94(16),8378-8379 [DOI: 10.1073/pnas.94.16.8378]
Awad N.S.; Paul V.; Mahmoud M.S.; Al Sawaftah N.M.; Kawak P.S.; Al Sayah M.H.; Husseini G.A.; Effect of pegylation and targeting moieties on the ultrasound-mediated drug release from liposomes. ACS Biomater Sci Eng 2020,6(1),48-57 [DOI: 10.1021/acsbiomaterials.8b01301]
Haghiralsadat F.; Amoabediny G.; Helder M.N.; Naderinezhad S.; Sheikhha M.H.; Forouzanfar T.; Zandieh-doulabi B.; A comprehensive mathematical model of drug release kinetics from nano-liposomes, derived from optimization studies of cationic PEGylated liposomal doxorubicin formulations for drug-gene delivery. Artif Cells Nanomed Biotechnol 2018,46(1),169-177 [DOI: 10.1080/21691401.2017.1304403]
Mishra P.; Nayak B.; Dey R.K.; PEGylation in anti-cancer therapy: An overview. Asian J Pharm Sci 2016,11(3),337-348 [DOI: 10.1016/j.ajps.2015.08.011]
Ettinger A.R.; Pegaspargase (Oncaspar). J Pediatr Oncol Nurs 1995,12(1),46-48 [DOI: 10.1177/104345429501200110]
Abuchowski A.; Kazo G.M.; Verhoest C.R.; Van Es T.; Kafkewitz D.; Nucci M.L.; Viau A.T.; Davis F.F.; Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates. Cancer Biochem Biophys 1984,7(2),175-186 [PMID: 6467175]
Hershfield M.S.; Buckley R.H.; Greenberg M.L.; Melton A.L.; Schiff R.; Hatem C.; Kurtzberg J.; Markert M.L.; Kobayashi R.H.; Kobayashi A.L.; Abuchowski A.; Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 1987,316(10),589-596 [DOI: 10.1056/NEJM198703053161005]
Li W.; Zhan P.; De Clercq E.; Lou H.; Liu X.; Current drug research on PEGylation with small molecular agents. Prog Polym Sci 2013,38(3-4),421-444 [DOI: 10.1016/j.progpolymsci.2012.07.006]
Park E.J.; Choi J.; Lee K.C.; Na D.H.; Emerging PEGylated non-biologic drugs. Expert Opin Emerg Drugs 2019,24(2),107-119 [DOI: 10.1080/14728214.2019.1604684]
Asano S.; Gavrilyuk J.; Burton D.R.; Barbas C.F.; III Preparation and activities of macromolecule conjugates of the CCR5 antagonist Maraviroc. ACS Med Chem Lett 2014,5(2),133-137 [DOI: 10.1021/ml400370w]
Xiao Q.; Bécar N.A.; Brown N.P.; Smith M.S.; Stern K.L.; Draper S.R.E.; Thompson K.P.; Price J.L.; Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect. Org Biomol Chem 2018,16(46),8933-8939 [DOI: 10.1039/C8OB02535E]
Verma P.; Dayal S.; Jain V.K.; Amrani A.; Alopecia universalis as a side effect of pegylated interferon α-ribavirin combination therapy for hepatitis C: A rare case report. J Chemother 2017,29(6),380-382 [DOI: 10.1080/1120009X.2016.1245235]
Knauf M.J.; Bell D.P.; Hirtzer P.; Luo Z.P.; Young J.D.; Katre N.V.; Relationship of effective molecular size to systemic clearance in rats of recombinant interleukin-2 chemically modified with water-soluble polymers. J Biol Chem 1988,263(29),15064-15070 [DOI: 10.1016/S0021-9258(18)68146-3]
Caliceti P.; Veronese F.M.; Pharmacokinetic and biodistribution properties of poly(ethylene glycol)–protein conjugates. Adv Drug Deliv Rev 2003,55(10),1261-1277 [DOI: 10.1016/S0169-409X(03)00108-X]
Fu M.; Zhuang X.; Zhang T.; Guan Y.; Meng Q.; Zhang Y.; PEGylated leuprolide with improved pharmacokinetic properties. Bioorg Med Chem 2020,28(4),115306 [DOI: 10.1016/j.bmc.2020.115306]
Katre N.V.; The conjugation of proteins with polyethylene glycol and other polymers. Adv Drug Deliv Rev 1993,10(1),91-114 [DOI: 10.1016/0169-409X(93)90005-O]
Zhou J.Q.; He T.; Wang J.W.; PEGylation of cytochrome c at the level of lysine residues mediated by a microbial transglutaminase. Biotechnol Lett 2016,38(7),1121-1129 [DOI: 10.1007/s10529-016-2083-6]
da Silva Freitas D.; Mero A.; Pasut G.; Chemical and enzymatic site specific PEGylation of hGH. Bioconjug Chem 2013,24(3),456-463 [DOI: 10.1021/bc300594y]
Gonzلlez-Valdez J.; Cueto L.F.; Benavides J.; Rito-Palomares M.; Potential application of aqueous two-phase systems for the fractionation of RNase A and α-Lactalbumin from their PEGylated conjugates. J Chem Technol Biotechnol 2011,86(1),26-33 [DOI: 10.1002/jctb.2507]
Pasut G.; Veronese F.M.; State of the art in PEGylation: The great versatility achieved after forty years of research. J Control Release 2012,161(2),461-472 [DOI: 10.1016/j.jconrel.2011.10.037]
Rajender Reddy K.; Modi M.W.; Pedder S.; Use of peginterferon alfa-2a (40 KD) (Pegasys) for the treatment of hepatitis C. Adv Drug Deliv Rev 2002,54(4),571-586 [DOI: 10.1016/S0169-409X(02)00028-5]
Foser S.; Schacher A.; Weyer K.A.; Brugger D.; Dietel E.; Marti S.; Schreitmüller T.; Isolation, structural characterization, and antiviral activity of positional isomers of monopegylated interferon α-2a (PEGASYS). Protein Expr Purif 2003,30(1),78-87 [DOI: 10.1016/S1046-5928(03)00055-X]
Grigoletto A.; Mero A.; Zanusso I.; Schiavon O.; Pasut G.; Chemical and Enzymatic Site Specific PEGylation of hGH: The Stability and in vivo Activity of PEG- N -Terminal-hGH and PEG-Gln141-hGH Conjugates. Macromol Biosci 2016,16(1),50-56 [DOI: 10.1002/mabi.201500282]
Luo S.; Lu X.; Liu C.; Zhong J.; Zhou L.; Chen T.; Site specific PEGylation of β-lactoglobulin at glutamine residues and its influence on conformation and antigenicity. Food Res Int 2019,123,623-630 [DOI: 10.1016/j.foodres.2019.05.038]
Molineux G.; The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr Pharm Des 2004,10(11),1235-1244 [DOI: 10.2174/1381612043452613]
Singh M.; Salnikova M.; Novel approaches and strategies for biologics, vaccines and cancer therapies 2015
Wang Y.; Langley R.J.; Tamshen K.; Harms J.; Middleditch M.J.; Maynard H.D.; Jamieson S.M.F.; Perry J.K.; Enhanced bioactivity of a human GHR antagonist generated by solid-phase site-specific PEGylation. Biomacromolecules 2021,22(2),299-308 [DOI: 10.1021/acs.biomac.0c01105]
Roberts M.J.; Bentley M.D.; Harris J.M.; Chemistry for peptide and protein PEGylation. Adv Drug Deliv Rev 2002,54(4),459-476 [DOI: 10.1016/S0169-409X(02)00022-4]
Veronese F.M.; Caliceti P.; Schiavon O.; Branched and linear Poly(Ethylene Glycol): Influence of the Polymer structure on enzymological, pharmacokinetic, and immunological properties of protein conjugates. J Bioact Compat Polym 1997,12(3),196-207 [DOI: 10.1177/088391159701200303]
Gokarn Y.R.; McLean M.; Laue T.M.; Effect of PEGylation on protein hydrodynamics. Mol Pharm 2012,9(4),762-773 [DOI: 10.1021/mp200470c]
Pfister D.; Morbidelli M.; Process for protein PEGylation. J Control Release 2014,180,134-149 [DOI: 10.1016/j.jconrel.2014.02.002]
Constantinou A.; Chen C.; Deonarain M.P.; Modulating the pharmacokinetics of therapeutic antibodies. Biotechnol Lett 2010,32(5),609-622 [DOI: 10.1007/s10529-010-0214-z]
Kim J.; Kong Y.P.; Niedzielski S.M.; Singh R.K.; Putnam A.J.; Shikanov A.; Characterization of the crosslinking kinetics of multi-arm poly(ethylene glycol) hydrogels formed via Michael-type addition. Soft Matter 2016,12(7),2076-2085 [DOI: 10.1039/C5SM02668G]
Adkins C.E.; Nounou M.I.; Hye T.; Mohammad A.S.; Terrell-Hall T.; Mohan N.K.; Eldon M.A.; Hoch U.; Lockman P.R.; NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer. BMC Cancer 2015,15(1),685 [DOI: 10.1186/s12885-015-1672-4]
Garrett C.R.; Bekaii-Saab T.S.; Ryan T.; Fisher G.A.; Clive S.; Kavan P.; Shacham-Shmueli E.; Buchbinder A.; Goldberg R.M.; Randomized phase 2 study of pegylated SN-38 (EZN-2208) or irinotecan plus cetuximab in patients with advanced colorectal cancer. Cancer 2013,119(24),4223-4230 [DOI: 10.1002/cncr.28358]
Charych D.H.; Hoch U.; Langowski J.L.; Lee S.R.; Addepalli M.K.; Kirk P.B.; Sheng D.; Liu X.; Sims P.W.; VanderVeen L.A.; Ali C.F.; Chang T.K.; Konakova M.; Pena R.L.; Kanhere R.S.; Kirksey Y.M.; Ji C.; Wang Y.; Huang J.; Sweeney T.D.; Kantak S.S.; Doberstein S.K.; NKTR-214, an engineered cytokine with biased IL2 receptor binding, increased tumor exposure, and marked efficacy in mouse tumor models. Clin Cancer Res 2016,22(3),680-690 [DOI: 10.1158/1078-0432.CCR-15-1631]
Zalipsky S.; Functionalized poly(ethylene glycol) for preparation of biologically relevant conjugates. Bioconjug Chem 1995,6(2),150-165 [DOI: 10.1021/bc00032a002]
Zalipsky S.; Chemistry of polyethylene glycol conjugates with biologically active molecules. Adv Drug Deliv Rev 1995,16(2-3),157-182 [DOI: 10.1016/0169-409X(95)00023-Z]
Harris J.M.; Laboratory synthesis of polyethylene glycol derivatives. J Macromol Sci 1985,25(3),325-373
Dust J.M.; Fang Z.H.; Harris J.M.; Proton NMR characterization of poly(ethylene glycols) and derivatives. Macromolecules 1990,23(16),3742-3746 [DOI: 10.1021/ma00218a005]
A branched methoxy 40 KDA polyethylene glycol (PEG) moiety optimizes the pharmacokinetics (PK) of peginterferon a-2A (PEGIFN) and may explain its enhanced efficacy in chronic hepatitis C (CHC) Available From: https://www.natap.org/2000/7thcroi/37rpt22300.html1999
Bailon P.; Palleroni A.; Schaffer C.A.; Spence C.L.; Fung W.J.; Porter J.E.; Ehrlich G.K.; Pan W.; Xu Z.X.; Modi M.W.; Farid A.; Berthold W.; Graves M.; Rational design of a potent, long-lasting form of interferon: A 40 kDa branched polyethylene glycol-conjugated interferon α-2a for the treatment of hepatitis C. Bioconjug Chem 2001,12(2),195-202 [DOI: 10.1021/bc000082g]
Swierczewska M.; Lee K.C.; Lee S.; What is the future of PEGylated therapies? Expert Opin Emerg Drugs 2015,20(4),531-536 [DOI: 10.1517/14728214.2015.1113254]
Metelsky S.T.; Dependence of the apparent thickness of the unstirred layer at the intestinal mucosa on nutrient concentration. Biophysics 2007,52(4),423-425 [DOI: 10.1134/S0006350907040124]
Madonov P.G.; Svyatchenko V.A.; Legostaev S.S.; Kikhtenko N.A.; Kotlyarova A.A.; Oleinik L.A.; Baikalov G.I.; Evaluation of the anti-viral activity of human recombinant interferon Lambda-1 against SARS-CoV-2. Bull Exp Biol Med 2021,172(1),53-56 [DOI: 10.1007/s10517-021-05330-0]
Sherstoboev E.Y.; Oleinik L.A.; Zhdanov V.V.; Kikhtenko N.A.; Madonov P.G.; Pharmacokinetic parameters of oral Pegylated IFN-λ1. Bull Exp Biol Med 2022,173(2),215-218 [DOI: 10.1007/s10517-022-05521-3]
Chan K.; Mong M.; Yin M.; Antioxidative and anti-inflammatory neuroprotective effects of astaxanthin and canthaxanthin in nerve growth factor differentiated PC12 cells. J Food Sci 2009,74(7),H225-H231 [DOI: 10.1111/j.1750-3841.2009.01274.x]
Park J.H.; Yeo I.J.; Han J.H.; Suh J.W.; Lee H.P.; Hong J.T.; Anti-inflammatory effect of astaxanthin in phthalic anhydride-induced atopic dermatitis animal model. Exp Dermatol 2018,27(4),378-385 [DOI: 10.1111/exd.13437]
Maoka T.; Tokuda H.; Suzuki N.; Kato H.; Etoh H.; Anti-oxidative, anti-tumor-promoting, and anti-carcinogensis activities of nitroastaxanthin and nitrolutein, the reaction products of astaxanthin and lutein with peroxynitrite. Mar Drugs 2012,10(12),1391-1399 [DOI: 10.3390/md10061391]
Zhang L.; Wang H.; Multiple mechanisms of anti-cancer effects exerted by Astaxanthin. Mar Drugs 2015,13(7),4310-4330 [DOI: 10.3390/md13074310]
Takemoto M.; Yamaga M.; Furuichi Y.; Yokote K.; Astaxanthin improves nonalcoholic fatty liver disease in werner syndrome with diabetes mellitus. J Am Geriatr Soc 2015,63(6),1271-1273 [DOI: 10.1111/jgs.13505]
Sifi N.; Martin-Eauclaire M.F.; Laraba-Djebari F.K.; + channel blocker-induced neuroinflammatory response and neurological disorders: Immunomodulatory effects of astaxanthin. Inflamm Res 2016,65(8),623-634 [DOI: 10.1007/s00011-016-0945-y]
Li Y.; Kang T.; Wu Y.; Chen Y.; Zhu J.; Gou M.; Carbonate esters turn camptothecin-unsaturated fatty acid prodrugs into nanomedicines for cancer therapy. Chem Commun 2018,54(16),1996-1999 [DOI: 10.1039/C8CC00639C]
Liu Y.; Yang L.; Guo Y.; Zhang T.; Qiao X.; Wang J.; Xu J.; Xue C.; Hydrophilic Astaxanthin: PEGylated Astaxanthin fights diabetes by enhancing the solubility and oral absorbability. J Agric Food Chem 2020,68(11),3649-3655 [DOI: 10.1021/acs.jafc.0c00784]
Kouchakzadeh H.; Shojaosadati S.A.; Maghsoudi A.; Vasheghani Farahani E.; Optimization of PEGylation conditions for BSA nanoparticles using response surface methodology. AAPS PharmSciTech 2010,11(3),1206-1211 [DOI: 10.1208/s12249-010-9487-8]
Zhang X.; Pan S.R.; Hu H.M.; Wu G.F.; Feng M.; Zhang W.; Luo X.; Poly(ethylene glycol)-block-polyethylenimine copolymers as carriers for gene delivery: Effects of PEG molecular weight and PEGylation degree. J Biomed Mater Res A 2008,84A(3),795-804 [DOI: 10.1002/jbm.a.31343]
Tahmasbi Rad A.; Chen C.W.; Aresh W.; Xia Y.; Lai P.S.; Nieh M.P.; Combinational effects of active targeting, shape, and enhanced permeability and retention for cancer theranostic nanocarriers. ACS Appl Mater Interfaces 2019,11(11),10505-10519 [DOI: 10.1021/acsami.8b21609]
Yoshikawa T.; Mori Y.; Feng H.; Phan K.Q.; Kishimura A.; Kang J.H.; Mori T.; Katayama Y.; Rapid and continuous accumulation of nitric oxide-releasing liposomes in tumors to augment the enhanced permeability and retention (EPR) effect. Int J Pharm 2019,565,481-487 [DOI: 10.1016/j.ijpharm.2019.05.043]
Ming L.J.; Epperson J.D.; Metal binding and structure–activity relationship of the metalloantibiotic peptide bacitracin. J Inorg Biochem 2002,91(1),46-58 [DOI: 10.1016/S0162-0134(02)00464-6]
Smith J.L.; Weinberg E.D.; Mechanisms of antibacterial action of bacitracin. J Gen Microbiol 1962,28(3),559-569 [DOI: 10.1099/00221287-28-3-559]
Hancock R.; Fitz-James P.C.; Some differences in the action of penicillin, bacitracin, and vancomycin on Bacillus megaterium. J Bacteriol 1964,87(5),1044-1050 [DOI: 10.1128/jb.87.5.1044-1050.1964]
Hong W.; Gao X.; Qiu P.; Yang J.; Qiao M.; Shi H.; Zhang D.; Tian C.; Niu S.; Liu M.; Synthesis, construction, and evaluation of self-assembled nano-bacitracin A as an efficient antibacterial agent in vitro and in vivo. Int J Nanomedicine 2017,12,4691-4708 [DOI: 10.2147/IJN.S136998]
Hong W.; Zhao Y.; Guo Y.; Huang C.; Qiu P.; Zhu J.; Chu C.; Shi H.; Liu M.; PEGylated self-assembled nano-bacitracin A: Probing the antibacterial mechanism and real-time tracing of target delivery in vivo. ACS Appl Mater Interfaces 2018,10(13),10688-10705 [DOI: 10.1021/acsami.8b00135]
Soe Z.C.; Ou W.; Gautam M.; Poudel K.; Kim B.K.; Pham L.M.; Phung C.D.; Jeong J.H.; Jin S.G.; Choi H.G.; Ku S.K.; Yong C.S.; Kim J.O.; Development of folate-functionalized pegylated zein nanoparticles for ligand-directed delivery of paclitaxel. Pharmaceutics 2019,11(11),562 [DOI: 10.3390/pharmaceutics11110562]
Zeng N.; Hu Q.; Liu Z.; Gao X.; Hu R.; Song Q.; Gu G.; Xia H.; Yao L.; Pang Z.; Jiang X.; Chen J.; Fang L.; Preparation and characterization of paclitaxel-loaded DSPE-PEG-liquid crystalline nanoparticles (LCNPs) for improved bioavailability. Int J Pharm 2012,424(1-2),58-66 [DOI: 10.1016/j.ijpharm.2011.12.058]
Phung C.D.; Tran T.H.; Kim J.O.; Engineered nanoparticles to enhance natural killer cell activity towards onco-immunotherapy: A review. Arch Pharm Res 2020,43(1),32-45 [DOI: 10.1007/s12272-020-01218-1]
Cho H.J.; Recent progresses in the development of hyaluronic acid-based nanosystems for tumor-targeted drug delivery and cancer imaging. J Pharm Investig 2020,50(2),115-129 [DOI: 10.1007/s40005-019-00448-w]
Tran B.N.; Nguyen H.T.; Kim J.O.; Yong C.S.; Nguyen C.N.; Developing combination of artesunate with paclitaxel loaded into poly- D,L -lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response. Drug Dev Ind Pharm 2017,43(12),1952-1962 [DOI: 10.1080/03639045.2017.1357729]
Aung W.; Sogawa C.; Furukawa T.; Saga T.; Anticancer effect of dihydroartemisinin (DHA) in a pancreatic tumor model evaluated by conventional methods and optical imaging. Anticancer Res 2011,31(5),1549-1558 [PMID: 21617209]
Chen Y.; Chin B.W.; Bieber M.M.; Tan X.; Teng N.N.; Abstract 470: Artemisinin derivatives synergize with paclitaxel by targeting FOXM1 through Raf/MEK/MAPK signaling pathway in ovarian cancer. Cancer Res 2014,74,470-470 [DOI: 10.1158/1538-7445.AM2014-470]
Wang L.; Wang Y.; Wang X.; Sun L.; Zhou Z.; Lu J.; Zheng Y.; Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity. J Microencapsul 2016,33(1),43-52 [DOI: 10.3109/02652048.2015.1114042]
Phung C.D.; Le T.G.; Nguyen V.H.; Vu T.T.; Nguyen H.Q.; Kim J.O.; Yong C.S.; Nguyen C.N.; PEGylated-Paclitaxel and dihydroartemisinin nanoparticles for simultaneously delivering paclitaxel and dihydroartemisinin to colorectal cancer. Pharm Res 2020,37(7),129 [DOI: 10.1007/s11095-020-02819-7]
Wilson R.C.; Doudna J.A.; Molecular mechanisms of RNA interference. Annu Rev Biophys 2013,42(1),217-239 [DOI: 10.1146/annurev-biophys-083012-130404]
Chen X.; Mangala L.S.; Rodriguez-Aguayo C.; Kong X.; Lopez-Berestein G.; Sood A.K.; RNA interference-based therapy and its delivery systems. Cancer Metastasis Rev 2018,37(1),107-124 [DOI: 10.1007/s10555-017-9717-6]
Xia Y.; Tian J.; Chen X.; Effect of surface properties on liposomal siRNA delivery. Biomaterials 2016,79,56-68 [DOI: 10.1016/j.biomaterials.2015.11.056]
Hatakeyama H.; Akita H.; Harashima H.; The polyethyleneglycol dilemma: Advantage and disadvantage of PEGylation of liposomes for systemic genes and nucleic acids delivery to tumors. Biol Pharm Bull 2013,36(6),892-899 [DOI: 10.1248/bpb.b13-00059]
Hattori Y.; Tamaki K.; Sakasai S.; Ozaki K.I.; Onishi H.; Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene silencing effects and siRNA biodistribution in mice. Mol Med Rep 2020,22(5),4183-4196 [DOI: 10.3892/mmr.2020.11525]
Zhang X.; Wang H.; Ma Z.; Wu B.; Effects of pharmaceutical PEGylation on drug metabolism and its clinical concerns. Expert Opin Drug Metab Toxicol 2014,10(12),1691-1702 [DOI: 10.1517/17425255.2014.967679]
Hoguet V.; Lasalle M.; Maingot M.; Dequirez G.; Boulahjar R.; Leroux F.; Piveteau C.; Herledan A.; Biela A.; Dumont J.; Chلvez-Talavera O.; Belloy L.; Duplan I.; Hennuyer N.; Butruille L.; Lestavel S.; Sevin E.; Culot M.; Gosselet F.; Staels B.; Deprez B.; Tailleux A.; Charton J.; Beyond the rule of 5: Impact of PEGylation with various polymer sizes on pharmacokinetic properties, structure–properties relationships of mPEGylated small agonists of TGR5 receptor. J Med Chem 2021,64(3),1593-1610 [DOI: 10.1021/acs.jmedchem.0c01774]
Manjili H.K.; Malvandi H.; Mousavi M.S.; Attari E.; Danafar H.; In vitro and in vivo delivery of artemisinin loaded PCL–PEG–PCL micelles and its pharmacokinetic study. Artif Cells Nanomed Biotechnol 2018,46(5),926-936 [DOI: 10.1080/21691401.2017.1347880]
Lu X.; Lu D.; Scully M.; Kakkar V.; The role of integrins in cancer and the development of anti-integrin therapeutic agents for cancer therapy. Perspect Medicin Chem 2008,2,57-73 [DOI: 10.1177/1177391X0800200003]
Vogetseder A.; Thies S.; Ingold B.; Roth P.; Weller M.; Schraml P.; Goodman S.L.; Moch H.; αv-Integrin isoform expression in primary human tumors and brain metastases. Int J Cancer 2013,133(10),2362-2371 [DOI: 10.1002/ijc.28267]
Bandyopadhyay A.; Raghavan S.; Defining the role of integrin alphavbeta6 in cancer. Curr Drug Targets 2009,10(7),645-652 [DOI: 10.2174/138945009788680374]
Kimura R.H.; Teed R.; Hackel B.J.; Pysz M.A.; Chuang C.Z.; Sathirachinda A.; Willmann J.K.; Gambhir S.S.; Pharmacokinetically stabilized cystine knot peptides that bind alpha-v-beta-6 integrin with single-digit nanomolar affinities for detection of pancreatic cancer. Clin Cancer Res 2012,18(3),839-849 [DOI: 10.1158/1078-0432.CCR-11-1116]
Hausner S.H.; Abbey C.K.; Bold R.J.; Gagnon M.K.; Marik J.; Marshall J.F.; Stanecki C.E.; Sutcliffe J.L.; Targeted in vivo imaging of integrin alphavbeta6 with an improved radiotracer and its relevance in a pancreatic tumor model. Cancer Res 2009,69(14),5843-5850 [DOI: 10.1158/0008-5472.CAN-08-4410]
Hausner S.H.; Bauer N.; Hu L.Y.; Knight L.M.; Sutcliffe J.L.; The effect of Bi-Terminal PEGylation of an integrin α v β 6 –Targeted 18 F peptide on pharmacokinetics and tumor uptake. J Nucl Med 2015,56(5),784-790 [DOI: 10.2967/jnumed.114.150680]
Xu J.; Sun T.; Zhong R.; You C.; Tian M.; PEGylation of deferoxamine for improving the stability, cytotoxicity, and iron-overload in an experimental stroke model in rats. Front Bioeng Biotechnol 2020,8,592294 [DOI: 10.3389/fbioe.2020.592294]
Sun J.; Wu J.; Jin H.; Ying T.; Jin W.; Fan M.; Zhou J.; Chen H.; Jin L.; Zhou J.; Structure-guided PEGylated fibroblast growth factor 2 variants accelerate wound healing with improved stability. Authorea 2020,1-18 [DOI: 10.22541/au.158870115.54235041]
Ladwig G.P.; Robson M.C.; Liu R.; Kuhn M.A.; Muir D.F.; Schultz G.S.; Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers. Wound Repair Regen 2002,10(1),26-37 [DOI: 10.1046/j.1524-475X.2002.10903.x]
Xu H.L.; Chen P.P.; Wang L.F.; Tong M.Q.; Ou Z.; Zhao Y.Z.; Xiao J.; Fu T.L.; Wei-Xue, Skin-permeable liposome improved stability and permeability of bFGF against skin of mice with deep second degree scald to promote hair follicle neogenesis through inhibition of scar formation. Colloids Surf B Biointerfaces 2018,172,573-585 [DOI: 10.1016/j.colsurfb.2018.09.006]
Peng G.; Pan X.; Hu H.; Xu Y.; Wu C.; N-terminal site-specific PEGylation enhances the circulation half-life of Thymosin alpha 1. J Drug Deliv Sci Technol 2019,49,405-412 [DOI: 10.1016/j.jddst.2018.09.009]
Seo H.; Bae H.D.; Pyun H.; Kim B.G.; Lee S.I.; Song J.S.; Lee K.; PEGylation improves the therapeutic potential of dimerized translationally controlled tumor protein blocking peptide in ovalbumin-induced mouse model of airway inflammation. Drug Deliv 2022,29(1),2320-2329 [DOI: 10.1080/10717544.2022.2100511]
Zbyszynski P.; Tomasini-Johansson B.R.; Peters D.M.; Kwon G.S.; Characterization of the PEGylated Functional Upstream Domain Peptide (PEG-FUD): A potent fibronectin assembly inhibitor with potential as an anti-fibrotic therapeutic. Pharm Res 2018,35(7),126 [DOI: 10.1007/s11095-018-2412-7]
Hui Y.F.; Reitz J.; Gemcitabine: A cytidine analogue active against solid tumors. Am J Health Syst Pharm 1997,54(2),162-170 [DOI: 10.1093/ajhp/54.2.162]
Abdalla M.Y.; Ahmad I.M.; Rachagani S.; Banerjee K.; Thompson C.M.; Maurer H.C.; Olive K.P.; Bailey K.L.; Britigan B.E.; Kumar S.; Enhancing responsiveness of pancreatic cancer cells to gemcitabine treatment under hypoxia by heme oxygenase-1 inhibition. Transl Res 2019,207,56-69 [DOI: 10.1016/j.trsl.2018.12.008]
Barton-Burke M.; Gemcitabine: A pharmacologic and clinical overview. Cancer Nurs 1999,22(2),176-183 [DOI: 10.1097/00002820-199904000-00011]
Chiappori A.A.; Rocha-Lima C.M.; New agents in the treatment of small-cell lung cancer: Focus on gemcitabine. Clin Lung Cancer 2003,4(Suppl. 2),S56-S63 [DOI: 10.3816/CLC.2003.s.005]
van Nuland M.; Hillebrand M.J.X.; Rosing H.; Burgers J.A.; Schellens J.H.M.; Beijnen J.H.; Ultra-sensitive LC–MS/MS method for the quantification of gemcitabine and its metabolite 2′2′-difluorodeoxyuridine in human plasma for a microdose clinical trial. J Pharm Biomed Anal 2018,151,25-31 [DOI: 10.1016/j.jpba.2017.12.048]
Xu Y.; Keith B.; Grem J.L.; Measurement of the anticancer agent gemcitabine and its deaminated metabolite at low concentrations in human plasma by liquid chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004,802(2),263-270 [DOI: 10.1016/j.jchromb.2003.11.038]
Storniolo A.M.; Allerheiligen S.R.; Pearce H.L.; Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol 1997,24(2 Suppl 7),S7-2-S7-7
Robinson K.; Lambiase L.; Li J.; Monteiro C.; Schiff M.; Fatal cholestatic liver failure associated with gemcitabine therapy. Dig Dis Sci 2003,48(9),1804-1808 [DOI: 10.1023/A]
Yin L.; Ren T.; Zhao S.; Shi M.; Gu J.; Comparative pharmacokinetic study of PEGylated gemcitabine and gemcitabine in rats by LC-MS/MS coupled with pre-column derivatization and MSALL technique. Talanta 2020,206,120184 [DOI: 10.1016/j.talanta.2019.120184]
Liu J.; Zhang Y.; Qu J.; Xu L.; Hou K.; Zhang J.; Qu X.; Liu Y.; β-Elemene-induced autophagy protects human gastric cancer cells from undergoing apoptosis. BMC Cancer 2011,11(1),183 [DOI: 10.1186/1471-2407-11-183]
Wu X.S.; Xie T.; Lin J.; Fan H.Z.; Huang-Fu H.J.; Ni L.F.; Yan H.F.; An investigation of the ability of elemene to pass through the blood-brain barrier and its effect on brain carcinomas. J Pharm Pharmacol 2010,61(12),1653-1656 [DOI: 10.1211/jpp.61.12.0010]
Chen M.; Wang S.; Tan M.; Wang Y.; Applications of nanoparticles in herbal medicine: Zedoary turmeric oil and its active compound β-elemene. Am J Chin Med 2011,39(6),1093-1102 [DOI: 10.1142/S0192415X11009421]
Zhai B.; Wu Q.; Wang W.; Zhang M.; Han X.; Li Q.; Chen P.; Chen X.; Huang X.; Li G.; Zhang Q.; Zhang R.; Xiang Y.; Liu S.; Duan T.; Lou J.; Xie T.; Sui X.; Preparation, characterization, pharmacokinetics and anticancer effects of PEGylated β-elemene liposomes. Cancer Biol Med 2020,17(1),60-75 [DOI: 10.20892/j.issn.2095-3941.2019.0156]
Srivastava A.; Brewer A.K.; Mauser-Bunschoten E.P.; Key N.S.; Kitchen S.; Llinas A.; Ludlam C.A.; Mahlangu J.N.; Mulder K.; Poon M.C.; Street A.; Guidelines for the management of hemophilia. Haemophilia 2013,19(1),e1-e47 [DOI: 10.1111/j.1365-2516.2012.02909.x]
Gringeri A.; Lundin B.; Von MacKensen S.; Mantovani L.; Mannucci P.M.; A randomized clinical trial of prophylaxis in children with hemophilia A (the ESPRIT Study). J Thromb Haemost 2011,9(4),700-710 [DOI: 10.1111/j.1538-7836.2011.04214.x]
Manco-Johnson M.J.; Abshire T.C.; Shapiro A.D.; Riske B.; Hacker M.R.; Kilcoyne R.; Ingram J.D.; Manco-Johnson M.L.; Funk S.; Jacobson L.; Valentino L.A.; Hoots W.K.; Buchanan G.R.; DiMichele D.; Recht M.; Brown D.; Leissinger C.; Bleak S.; Cohen A.; Mathew P.; Matsunaga A.; Medeiros D.; Nugent D.; Thomas G.A.; Thompson A.A.; McRedmond K.; Soucie J.M.; Austin H.; Evatt B.L.; Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia. N Engl J Med 2007,357(6),535-544 [DOI: 10.1056/NEJMoa067659]
Collins P.W.; Blanchette V.S.; Fischer K.; Bjِrkman S.; Oh M.; Fritsch S.; Schroth P.; Spotts G.; Astermark J.; Ewenstein B.; Break‐through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A. J Thromb Haemost 2009,7(3),413-420 [DOI: 10.1111/j.1538-7836.2008.03270.x]
Mei B.; Pan C.; Jiang H.; Tjandra H.; Strauss J.; Chen Y.; Liu T.; Zhang X.; Severs J.; Newgren J.; Chen J.; Gu J.M.; Subramanyam B.; Fournel M.A.; Pierce G.F.; Murphy J.E.; Rational design of a fully active, long-acting PEGylated factor VIII for hemophilia A treatment. Blood 2010,116(2),270-279 [DOI: 10.1182/blood-2009-11-254755]
Röstin J.; Smeds A.L.; Åkerblom E.; B-Domain deleted recombinant coagulation factor VIII modified with monomethoxy polyethylene glycol. Bioconjug Chem 2000,11(3),387-396 [DOI: 10.1021/bc990137i]
Shah A.; Solms A.; Wiegmann S.; Ahsman M.; Berntorp E.; Tiede A.; Iorio A.; Mancuso M.E.; Zhivkov T.; Lissitchkov T.; Direct comparison of two extended-half-life recombinant FVIII products: A randomized, crossover pharmacokinetic study in patients with severe hemophilia A. Ann Hematol 2019,98(9),2035-2044 [DOI: 10.1007/s00277-019-03747-2]
Yu J.; Wang Y.; Zhou S.; Li J.; Wang J.; Chi D.; Wang X.; Lin G.; He Z.; Wang Y.; Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy. Acta Pharm Sin B 2020,10(9),1730-1740 [DOI: 10.1016/j.apsb.2020.04.011]
Zhao J.; Du J.; Wang J.; An N.; Zhou K.; Hu X.; Dong Z.; Liu Y.; Folic Acid and Poly(ethylene glycol) decorated paclitaxel nanocrystals exhibit enhanced stability and breast cancer-targeting capability. ACS Appl Mater Interfaces 2021,13(12),14577-14586 [DOI: 10.1021/acsami.1c00184]
Coelho S.C.; Rocha S.; Pereira M.C.; Juzenas P.; Coelho M.A.N.; Enhancing proteasome-lnhibitor effect by functionalized gold nanoparticles. J Biomed Nanotechnol 2014,10(4),717-723 [DOI: 10.1166/jbn.2014.1743]
Fischer D.; Li Y.; Ahlemeyer B.; Krieglstein J.; Kissel T.; In vitro cytotoxicity testing of polycations: Influence of polymer structure on cell viability and hemolysis. Biomaterials 2003,24(7),1121-1131 [DOI: 10.1016/S0142-9612(02)00445-3]
Hong S.; Leroueil P.R.; Janus E.K.; Peters J.L.; Kober M.M.; Islam M.T.; Orr B.G.; Baker J.R.; Banaszak Holl M.M.; Interaction of polycationic polymers with supported lipid bilayers and cells: Nanoscale hole formation and enhanced membrane permeability. Bioconjug Chem 2006,17(3),728-734 [DOI: 10.1021/bc060077y]
Sahoo R.K.; Gothwal A.; Rani S.; Nakhate K.T.; Ajazuddin ; Gupta U.; PEGylated dendrimer mediated delivery of bortezomib: Drug conjugation versus encapsulation. Int J Pharm 2020,584,119389 [DOI: 10.1016/j.ijpharm.2020.119389]
Mukherjee S.; Kotcherlakota R.; Haque S.; Bhattacharya D.; Kumar J.M.; Chakravarty S.; Patra C.R.; Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma. Mater Sci Eng C 2020,108,110375 [DOI: 10.1016/j.msec.2019.110375]
Mukherjee S.; Kotcherlakota R.; Haque S.; Das S.; Nuthi S.; Bhattacharya D.; Madhusudana K.; Chakravarty S.; Sistla R.; Patra C.R.; Silver prussian blue analogue nanoparticles: Rationally designed advanced nanomedicine for multifunctional biomedical applications. ACS Biomater Sci Eng 2020,6(1),690-704 [DOI: 10.1021/acsbiomaterials.9b01693]
Mukherjee S.; Bollu V.S.; Roy A.; Nethi S.K.; Madhusudana K.; Kumar J.M.; Sistla R.; Patra C.R.; Acute toxicity, biodistribution, and pharmacokinetics studies of Pegylated Platinum Nanoparticles in mouse model. Adv NanoBiomed Res 2021,1(7),2000082 [DOI: 10.1002/anbr.202000082]

MeSH Term

Humans
Polyethylene Glycols
Pharmaceutical Preparations
Animals
Drug Delivery Systems
Pharmacokinetics

Chemicals

Polyethylene Glycols
Pharmaceutical Preparations

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