PEGylation and Cell-Penetrating Peptides: Glimpse into the Past and Prospects in the Future

Author(s): Sumit Kumar, Devender Singh, Pooja Kumari, Rajender Singh Malik, Poonam, Keykavous Parang, Rakesh Kumar Tiwari*

Journal Name: Current Topics in Medicinal Chemistry

Volume 20 , Issue 5 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


Several drug molecules have shown low bioavailability and pharmacokinetic profile due to metabolism by enzymes, excretion by the renal system, or due to other physiochemical properties of drug molecules. These problems have resulted in the loss of efficacy and the gain of side effects associated with drug molecules. PEGylation is one of the strategies to overcome these pharmacokinetic issues and has been successful in the clinic. Cell-penetrating Peptides (CPPs) help to deliver molecules across biological membranes and could be used to deliver cargo selectively to the intracellular site or to the drug target. Hence CPPs could be used to improve the efficacy and selectivity of the drug. However, due to the peptidic nature of CPPs, they have a low pharmacokinetic profile. Using PEGylation and CPPs together as a component of a drug delivery system, the and efficacy of drug molecules could be improved. The other important pharmacokinetic properties such as short half-life, solubility, stability, absorption, metabolism, and elimination could be also improved. Here in this review, we summarized PEGylated CPPs or PEGylation based formulations for CPPs used in a drug delivery system for several biomedical applications until August 2019.

Keywords: Bioavailability, Cell-penetrating peptides, Cellular uptake, Drug delivery system, Polyethylene glycol, PEGylation, Stability, Toxicity.

Roberts, M.J.; Bentley, M.D.; Harris, J.M. Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev., 2012, 64, 116-127.
[] [PMID: 12052709]
Lau, J.L.; Dunn, M.K. Therapeutic peptides: Historical perspectives, current development trends, and future directions. Bioorg. Med. Chem., 2018, 26(10), 2700-2707.
[] [PMID: 28720325]
Pisal, D.S.; Kosloski, M.P.; Balu-Iyer, S.V. Delivery of therapeutic proteins. J. Pharm. Sci., 2010, 99(6), 2557-2575.
[] [PMID: 20049941]
Abuchowski, A.; McCoy, J.R.; Palczuk, N.C.; van Es, T.; Davis, F.F. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J. Biol.Chem., 1977, 252(11), 3582-3586.
[PMID: 16907]
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.
[PMID: 405385]
Kang, J.S.; Deluca, P.P.; Lee, K.C. Emerging PEGylated drugs. Expert Opin. Emerg. Drugs, 2009, 14(2), 363-380.
[] [PMID: 19453284]
Mishra, P.; Nayak, B.; Dey, R.K. PEGylation in anti-cancer therapy: An overview. Asian J. Pharm. Sci., 2016, 11(3), 337-348.
Veronese, F.M. Peptide and protein PEGylation: a review of problems and solutions. Biomaterials, 2001, 22(5), 405-417.
[] [PMID: 11214751]
Bunker, A. Poly (ethylene glycol) in drug delivery, why does it work, and can we do better? All atom molecular dynamics simulation provides some answers. Phys. Procedia, 2012, 34, 24-33.
Wang, X.L.; Xu, R.; Lu, Z.R. A peptide-targeted delivery system with pH-sensitive amphiphilic cell membrane disruption for efficient receptor-mediated siRNA delivery. J. Control. Release, 2009, 134(3), 207-213.
[] [PMID: 19135104]
Aldrian, G.; Vaissière, A.; Konate, K.; Seisel, Q.; Vivès, E.; Fernandez, F.; Viguier, V.; Genevois, C.; Couillaud, F.; Démèné, H.; Aggad, D.; Covinhes, A.; Barrère-Lemaire, S.; Deshayes, S.; Boisguerin, P. PEGylation rate influences peptide-based nanoparticles mediated siRNA delivery in vitro and in vivo. J. Control. Release, 2017, 256, 79-91.
[] [PMID: 28411182]
Canalle, L.A.; Löwik, D.W.P.M.; van Hest, J.C.M. Polypeptide-polymer bioconjugates. Chem. Soc. Rev., 2010, 39(1), 329-353.
[] [PMID: 20023856]
Rabotyagova, O.S.; Cebe, P.; Kaplan, D.L. Protein-based block copolymers. Biomacromolecules, 2011, 12(2), 269-289.
[] [PMID: 21235251]
Gauthier, M.A.; Klok, H.A. Peptide/protein-polymer conjugates: synthetic strategies and design concepts. Chem. Commun. (Camb.), 2008, (23), 2591-2611.
[] [PMID: 18535687]
Klok, H.A. Peptide/Protein-synthetic polymer conjugates: Quo Vadis. Macromolecules, 2009, 42, 7990-8000.
Delgado, C.; Francis, G.E.; Fisher, D. The uses and properties of PEG-linked proteins. Crit. Rev. Ther. Drug Carrier Syst., 1992, 9(3-4), 249-304.
[PMID: 1458545]
Ryan, S.M.; Mantovani, G.; Wang, X.; Haddleton, D.M.; Brayden, D.J. Advances in PEGylation of important biotech molecules: delivery aspects. Expert Opin. Drug Deliv., 2008, 5(4), 371-383.
[] [PMID: 18426380]
Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U.S. Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl., 2010, 49(36), 6288-6308.
[] [PMID: 20648499]
Alconcel, S.N.S.; Baas, A.S.; Maynard, H.D. FDA-Approved Poly (ethylene glycol) −Protein conjugate drugs. Polym. Chem., 2011, 2, 1442-1448.
Zalipsky, S. Chemistry of polyethylene-glycol conjugates with biologically active molecules. Adv. Drug Deliv. Rev., 1995, 16, 157-182.
Hamley, I.W. PEG-peptide conjugates. Biomacromolecules, 2014, 15(5), 1543-1559.
[] [PMID: 24720400]
Tesauro, D.; Accardo, A.; Diaferia, C.; Milano, V.; Guillon, J.; Ronga, L.; Rossi, F. Peptide-based drug-delivery systems in biotechnological applications: recent advances and Perspectives. Molecules, 2019, 24(2), 351.
Järver, P.; Langel, U. Cell-penetrating peptides--a brief introduction. Biochim. Biophys. Acta, 2006, 1758(3), 260-263.
[] [PMID: 16574060]
Bruno, B.J.; Miller, G.D.; Lim, C.S. Basics and recent advances in peptide and protein drug delivery. Ther. Deliv., 2013, 4(11), 1443-1467.
[] [PMID: 24228993]
Bucci, M.; Gratton, J.P.; Rudic, R.D.; Acevedo, L.; Roviezzo, F.; Cirino, G.; Sessa, W.C. In vivo delivery of the caveolin-1 scaffolding domain inhibits nitric oxide synthesis and reduces inflammation. Nat. Med., 2000, 6(12), 1362-1367.
[] [PMID: 11100121]
Rousselle, C.; Clair, P.; Lefauconnier, J.M.; Kaczorek, M.; Scherrmann, J.M.; Temsamani, J. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. Mol. Pharmacol., 2000, 57(4), 679-686.
[] [PMID: 10727512]
Nasrolahi Shirazi, A.; Tiwari, R.; Chhikara, B.S.; Mandal, D.; Parang, K. Design and biological evaluation of cell-penetrating peptide-doxorubicin conjugates as prodrugs. Mol. Pharm., 2013, 10(2), 488-499.
[] [PMID: 23301519]
Chhikara, B.S.; Rathi, B.; Parang, K. Critical evaluation of pharmaceutical rational design of nano-delivery systems for Doxorubicin in cancer therapy. J. Mater. Nanosci., 2019, 6(2), 47-66.
Madani, F.; Lindberg, S.; Langel, U.; Futaki, S.; Gräslund, A. Mechanisms of cellular uptake of cell-penetrating peptides. J. Biophys., Article 2011.ID-414729, 1-10..
Hatakeyama, H.; Akita, H.; Harashima, H. A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv. Drug Deliv. Rev., 2011, 63(3), 152-160.
[] [PMID: 20840859]
Kurrikoff, K.; Gestin, M.; Langel, Ü. Recent in vivo advances in cell-penetrating peptide-assisted drug delivery. Expert Opin. Drug Deliv., 2016, 13(3), 373-387.
[] [PMID: 26634750]
Koren, E.; Torchilin, V.P. Cell-penetrating peptides: breaking through to the other side. Trends Mol. Med., 2012, 18(7), 385-393.
[] [PMID: 22682515]
Nigatu, A.S.; Vupputuri, S.; Flynn, N.; Ramsey, J.D. Effects of cell-penetrating peptides on transduction efficiency of PEGylated adenovirus. Biomed. Pharmacother., 2015, 71, 153-160.
[] [PMID: 25960231]
Benincasa, M.; Zahariev, S.; Pelillo, C.; Milan, A.; Gennaro, R.; Scocchi, M. PEGylation of the peptide Bac7(1-35) reduces renal clearance while retaining antibacterial activity and bacterial cell penetration capacity. Eur. J. Med. Chem., 2015, 95, 210-219.
[] [PMID: 25817771]
Yang, V.; Pedrosa, S.S.; Fernandes, R.; Maurício, A.C.; Koksch, B.; Gärtner, F.; Amorim, I.; Vale, N. Synthesis of PEGylated methotrexate conjugated with a novel CPP6, in sillico structural insights and activity in MCF-7 cells. J. Mol. Struct., 2019, 1192, 201-207.
Lee, S.H.; Moroz, E.; Castagner, B.; Leroux, J.C. Activatable cell penetrating peptide-peptide nucleic acid conjugate via reduction of azobenzene PEG chains. J. Am. Chem. Soc., 2014, 136(37), 12868-12871.
[] [PMID: 25185512]
Nguyen, J.; Xie, X.; Neu, M.; Dumitrascu, R.; Reul, R.; Sitterberg, J.; Bakowsky, U.; Schermuly, R.; Fink, L.; Schmehl, T.; Gessler, T.; Seeger, W.; Kissel, T. Effects of cell-penetrating peptides and pegylation on transfection efficiency of polyethylenimine in mouse lungs. J. Gene Med., 2008, 10(11), 1236-1246.
[] [PMID: 18780309]
Oh, E.; Delehanty, J.B.; Sapsford, K.E.; Susumu, K.; Goswami, R.; Blanco-Canosa, J.B.; Dawson, P.E.; Granek, J.; Shoff, M.; Zhang, Q.; Goering, P.L.; Huston, A.; Medintz, I.L. Cellular uptake and fate of PEGylated gold nanoparticles is dependent on both cell-penetration peptides and particle size. ACS Nano, 2011, 5(8), 6434-6448.
[] [PMID: 21774456]
Rosés, C.; Carbajo, D.; Sanclimensb, G.; Sinfreu, J.F.; Blancafort, A.; Oliveras, G.; Cirac, A.D.; Bardají, E.; Teresa Puig, T.; Planas, M.; Feliu, L.; Fernando Albericio, F.; Royo, M. Cell-penetratingγ-peptide/antimicrobial undecapeptide conjugates with anticancer activity. Tetrahedron, 2012, 68(23), 4406-4412.
Ziegler, A.; Seelig, J. Contributions of glycosaminoglycan binding and clustering to the biological uptake of the nonamphipathic cell-penetrating peptide WR9. Biochemistry, 2011, 50(21), 4650-4664.
[] [PMID: 21491915]
Baumhof, P.; Schlake, T. Disulfide-linked polyethylene glycol/peptide conjugates for the transfection of nucleic acids. U.S. Patent US8703906B2, 2014.
Ding, Y.; Sun, D.; Wang, G.L.; Yang, H.G.; Xu, H.F.; Chen, J.H.; Xie, Y.; Wang, Z.Q. An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery. Int. J. Nanomedicine, 2015, 10, 6199-6214.
[PMID: 26491292]
Koren, E.; Apte, A.; Jani, A.; Torchilin, V.P. Multifunctional PEGylated 2C5-immunoliposomes containing pH-sensitive bonds and TAT peptide for enhanced tumor cell internalization and cytotoxicity. J. Control. Release, 2012, 160(2), 264-273.
[] [PMID: 22182771]
Biswas, S.; Deshpande, P.P.; Perche, F.; Dodwadkar, N.S.; Sane, S.D.; Torchilin, V.P. Octa-arginine-modified pegylated liposomal doxorubicin: an effective treatment strategy for non-small cell lung cancer. Cancer Lett., 2013, 335(1), 191-200.
[] [PMID: 23419527]
Biswas, S.; Dodwadkar, N.S.; Deshpande, P.P.; Parab, S.; Torchilin, V.P. Surface functionalization of doxorubicin-loaded liposomes with octa-arginine for enhanced anticancer activity. Eur. J. Pharm. Biopharm., 2013, 84(3), 517-525.
[] [PMID: 23333899]
Zhang, Q.; Tang, J.; Fu, L.; Ran, R.; Liu, Y.; Yuan, M.; He, Q. A pH-responsive α-helical cell penetrating peptide-mediated liposomal delivery system. Biomaterials, 2013, 34(32), 7980-7993.
[] [PMID: 23891517]
Zhang, Y.; Zhang, L.; Hu, Y.; Jiang, K.; Li, Z.; Lin, Y.Z.; Wei, G.; Lu, W. Cell-permeable NF-κB inhibitor-conjugated liposomes for treatment of glioma. J. Control. Release, 2018, 289, 102-113.
[] [PMID: 30243823]
Barattin, M.; Mattarei, A.; Balasso, A.; Paradisi, C.; Cantù, L.; Del Favero, E.; Viitala, T.; Mastrotto, F.; Caliceti, P.; Salmaso, S. pH-controlled liposomes for enhanced cell penetration in tumor environment. ACS Appl. Mater. Interfaces, 2018, 10(21), 17646-17661.
[] [PMID: 29737834]
Apte, A.; Koren, E.; Koshkaryev, A.; Torchilin, V.P. Doxorubicin in TAT peptide-modified multifunctional immunoliposomes demonstrates increased activity against both drug-sensitive and drug-resistant ovarian cancer models. Cancer Biol. Ther., 2014, 15(1), 69-80.
[] [PMID: 24145298]
Teymouri, M.; Badiee, A.; Golmohammadzadeh, S.; Sadri, K.; Akhtari, J.; Mellat, M.; Nikpoor, A.R.; Jaafari, M.R. Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: An in vitro and in vivo study on drug cellular delivery, release, biodistribution and antitumor activity. Int. J. Pharm., 2016, 511(1), 236-244.
[] [PMID: 27363937]
Xie, X.; Kerrigan, J.E.; Minko, T.; Garbuzenko, O.; Lee, K.C.; Scarborough, A.; Abali, E.E.; Budak-Alpdogan, T.; Johnson-Farley, N.; Banerjee, D.; Scotto, K.W.; Bertino, J.R. Antitumor and modeling studies of a penetratin-peptide that targets E2F-1 in small cell lung cancer. Cancer Biol. Ther., 2013, 14(8), 742-751.
[] [PMID: 23792570]
Kuai, R.; Yuan, W.; Li, W.; Qin, Y.; Tang, J.; Yuan, M.; Fu, L.; Ran, R.; Zhang, Z.; He, Q. Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration. Mol. Pharm., 2011, 8(6), 2151-2161.
[] [PMID: 21981683]
Kibria, G.; Hatakeyama, H.; Ohga, N.; Hida, K.; Harashima, H. Dual-ligand modification of PEGylated liposomes shows better cell selectivity and efficient gene delivery. J. Control. Release, 2011, 153(2), 141-148.
[] [PMID: 21447361]
Fisher, R.K.; Mattern-Schain, S.I.; Best, M.D.; Kirkpatrick, S.S.; Freeman, M.B.; Grandas, O.H.; Mountain, D.J.H. Improving the efficacy of liposome-mediated vascular gene therapy via lipid surface modifications. J. Surg. Res., 2017, 219, 136-144.
[] [PMID: 29078873]
Janssen, A.P.; Schiffelers, R.M.; ten Hagen, T.L.; Koning, G.A.; Schraa, A.J.; Kok, R.J.; Storm, G.; Molema, G. Peptide-targeted PEG-liposomes in anti-angiogenic therapy. Int. J. Pharm., 2003, 254(1), 55-58.
[] [PMID: 12615409]
Osman, G.; Rodriguez, J.; Chan, S.Y.; Chisholm, J.; Duncan, G.; Kim, N.; Tatler, A.L.; Shakesheff, K.M.; Hanes, J.; Suk, J.S.; Dixon, J.E. PEGylated enhanced cell penetrating peptide nanoparticles for lung gene therapy. J. Control. Release, 2018, 285, 35-45.
[] [PMID: 30004000]
Khalil, I.A.; Harashima, H. An efficient PEGylated gene delivery system with improved targeting: Synergism between octaarginine and a fusogenic peptide. Int. J. Pharm., 2018, 538(1-2), 179-187.
[] [PMID: 29341911]
Perillo, E.; Hervé-Aubert, K.; Allard-Vannier, E.; Falanga, A.; Galdiero, S.; Chourpa, I. Synthesis and in vitro evaluation of fluorescent and magnetic nanoparticles functionalized with a cell penetrating peptide for cancer theranosis. J. Colloid Interface Sci., 2017, 499, 209-217.
[] [PMID: 28388503]
Li, Y.; Lee, R.J.; Yu, K.; Bi, Y.; Qi, Y.; Sun, Y.; Li, Y.; Xie, J.; Teng, L. Delivery of siRNA using lipid nanoparticles modified with cell penetrating peptide. ACS Appl. Mater. Interfaces, 2016, 8(40), 26613-26621.
[] [PMID: 27617513]
Cheng, C.J.; Saltzman, W.M. Enhanced siRNA delivery into cells by exploiting the synergy between targeting ligands and cell-penetrating peptides. Biomaterials, 2011, 32(26), 6194-6203.
[] [PMID: 21664689]
Gang, W.; Xiaoli, L.; Wenjian, Z.; Chang, L.; Weiyue, L. Cellpenetrating peptide-modified nanoparticle and preparation method.CN Patent 1,02,988,295 A, 2013.
Fields, R.J.; Cheng, C.J.; Quijano, E.; Weller, C.; Kristofik, N.; Duong, N.; Hoimes, C.; Egan, M.E.; Saltzman, W.M. Surface modified poly(β amino ester)-containing nanoparticles for plasmid DNA delivery. J. Control. Release, 2012, 164(1), 41-48.
[] [PMID: 23041278]
Malhotra, M.; Tomaro-Duchesneau, C.; Prakash, S. Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA delivery targeting neurodegenerative diseases. Biomaterials, 2013, 34(4), 1270-1280.
[] [PMID: 23140978]
Mok, H.; Bae, K.H.; Ahn, C.H.; Park, T.G. PEGylated and MMP-2 specifically dePEGylated quantum dots: comparative evaluation of cellular uptake. Langmuir, 2009, 25(3), 1645-1650.
[] [PMID: 19117377]
Choi, Y.; Kim, K.; Hong, S.; Kim, H.; Kwon, Y.J.; Song, R. Intracellular protein target detection by quantum dots optimized for live cell imaging. Bioconjug. Chem., 2011, 22(8), 1576-1586.
[] [PMID: 21718016]
Mahmoudi, A.; Jaafari, M.R.; Ramezanian, N.; Gholami, L.; Malaekeh-Nikouei, B. BR2 and CyLoP1 enhance in-vivo SN38 delivery using pegylated PAMAM dendrimers. Int. J. Pharm., 2019, 564, 77-89.
[] [PMID: 30991135]
Zhu, L.; Wang, T.; Perche, F.; Taigind, A.; Torchilin, V.P. Enhanced anticancer activity of nanopreparation containing an MMP2-sensitive PEG-drug conjugate and cell-penetrating moiety. Proc. Natl. Acad. Sci. USA, 2013, 110(42), 17047-17052.
[] [PMID: 24062440]
Liu, L.; Xie, H.J.; Mu, L.M.; Liu, R.; Su, Z.B.; Cui, Y.N.; Xie, Y.; Lu, W.L. Functional chlorin gold nanorods enable to treat breast cancer by photothermal/photodynamic therapy. Int. J. Nanomedicine, 2018, 13, 8119-8135.
[] [PMID: 30555230]
Chen, Y.; Zhang, M.; Jin, H.; Tang, Y.; Wu, A.; Xu, Q.; Huang, Y. Prodrug-like, PEGylated protein toxin trichosanthin for reversal of chemoresistance. Mol. Pharm., 2017, 14(5), 1429-1438.
[] [PMID: 28195491]
Teramura, Y.; Asif, S.; Ekdahl, K.N.; Gustafson, E.; Nilsson, B. Cell adhesion induced using surface modification with cell-penetrating peptide-conjugated poly (ethylene glycol)-lipid: A new cell glue for 3D cell-based structures. ACS Appl. Mater. Interfaces, 2017, 9(1), 244-254.
[] [PMID: 27976850]
Hu, S.; Wang, T.; Pei, X.; Cai, H.; Chen, J.; Zhang, X.; Wan, Q.; Wang, J. Synergistic enhancement of antitumor efficacy by PEGylated multi-walled carbon nanotubes modified with cell-penetrating peptide TAT. Nanoscale Res. Lett., 2016, 11(1), 452.
[] [PMID: 27726120]
Iwase, Y.; Kamei, N.; Khafagy, S.; Miyamoto, M.; Takeda-Morishita, M. Use of a non-covalent cell-penetrating peptide strategy to enhance the nasal delivery of interferon beta and its PEGylated form. Int. J. Pharm., 2016, 510(1), 304-310.
[] [PMID: 27343364]
Gefen, T.; Vaya, J.; Khatib, S.; Harkevich, N.; Artoul, F.; Heller, E.D.; Pitcovski, J.; Aizenshtein, E. The impact of PEGylation on protein immunogenicity. Int. Immunopharmacol., 2013, 15(2), 254-259.
[] [PMID: 23306102]
Caliceti, P.; Veronese, F.M. Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev., 2003, 55(10), 1261-1277.
[] [PMID: 14499706]
Calceti, P.; Salmaso, S.; Walker, G.; Bernkop-Schnürch, A. Development and in vivo evaluation of an oral insulin-PEG delivery system. Eur. J. Pharm. Sci., 2004, 22(4), 315-323.
[] [PMID: 15196588]
Sherman, M.R.; Saifer, M.G.P.; Williams, L.D.; Michaels, S.J.; Sobczyk, M.A. Next-generation PEGylation enables reduced immunoreactivity of PEG-protein conjugates. Drug Des. Deliv., 2012, 12(5), 36-41.
Perinelli, D.R.; Campana, M.; Singh, I.; Vllasaliu, D.; Doutch, J.; Palmieri, G.F.; Casettari, L. PEGylation affects the self-assembling behaviour of amphiphilic octapeptides. Int. J. Pharm., 2019, 571118752
[] [PMID: 31606529]
Laine, G.A.; Hossain, S.M.; Solis, R.T.; Adams, S.C. Polyethylene glycol nephrotoxicity secondary to prolonged high-dose intravenous lorazepam. Ann. Pharmacother., 1995, 29(11), 1110-1114.
[] [PMID: 8573954]
Choi, N.K.; Chang, Y.; Jung, S.Y.; Choi, Y.K.; Lee, J.; Lee, J.H.; Kim, J.Y.; Park, B.J. A population-based case-crossover study of polyethylene glycol use and acute renal failure risk in the elderly. World J. Gastroenterol., 2011, 17(5), 651-656.
[] [PMID: 21350715]
Ishida, T.; Ichihara, M.; Wang, X.; Kiwada, H. Spleen plays an important role in the induction of accelerated blood clearance of PEGylated liposomes. J. Control. Release, 2006, 115(3), 243-250.
[] [PMID: 17011060]
Lawrence, P.B.; Price, J.L. How PEGylation influences protein conformational stability. Curr. Opin. Chem. Biol., 2016, 34, 88-94.
[] [PMID: 27580482]
Hamidi, M.; Azadi, A.; Rafiei, P. Pharmacokinetic consequences of pegylation. Drug Deliv., 2006, 13(6), 399-409.
[] [PMID: 17002967]
Khutoryanskiy, V.V. Beyond PEGylation: Alternative surface-modification of nanoparticles with mucus-inert biomaterials. Adv. Drug Deliv. Rev., 2018, 124, 140-149.
[] [PMID: 28736302]
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.
[] [PMID: 30957581]
[Shang, E. P.; Sajid, M.I.; Parang, K.; Tiwari, R.K. Cyclic cell-penetrating peptides as efficient intracellular drug delivery tools. Mol. Pharm.,2019, 16(9), 3727-3743.]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [337 - 348]
Pages: 12
DOI: 10.2174/1568026620666200128142603
Price: $65

Article Metrics

PDF: 25