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6 PEGylation asaTool toAlter Immunological Properties ofNanocarriers
187
6.6.7 Cardiovascular (CVS) Drug Delivery
PEGylated nanocarriers can be utilized to deliver drugs for treating cardiovascular
diseases, such as atherosclerosis or hypertension. The nanocarriers can target specic sites in the vasculature, improving drug efcacy and reducing off-target effects
(Mohamed etal. 2022). PEGylated nanocarriers have shown great potential as drug
delivery systems for various therapeutic applications. The PEGylation strategy must
be carefully optimized to achieve the desired pharmacokinetic and biodistribution
properties while minimizing the risk of adverse reactions.
6.7 Challenges andFuture Perspectives
PEGylation is a complex technique often involving multistep synthesis methods.
Achieving high conjugation efciency and uniform distribution of PEG chains on
the nanocarrier surface is crucial for consistent performance. PEGylation involves
the use of PEG chains of varying lengths. The choice of PEG chain length can inuence the pharmacokinetics, biodistribution, and clearance of the nanocarriers.
Achieving consistent and controlled PEGylation with precise chain lengths can be
challenging, and variations in chain length can lead to unpredictable behavior and
efcacy. These issues highlight the manufacturing challenges associated with
PEGylated products. Hence, developing efcient PEGylation methods that ensure
uniform coverage and minimal batch-to-batch variability is an ongoing challenge
(Rabanel etal. 2014). The stability of the PEG coating is another concern related to
the PEGylated molecules. PEG chains can undergo degradation or detachment from
the nanocarriers’ surface over time, potentially impacting the stability and performance of PEGylated nanocarriers. Strategies to improve the stability and prevent
premature shedding of PEG chains are being explored (Sun etal. 2017).
PEGylation can limit the interaction of nanocarriers with target cells or tissues,
as the PEG chains create a steric barrier. Overcoming this challenge involves designing strategies to enhance targeting and cellular penetration while maintaining the
benets of PEGylation. PEGylated moieties can further be conjugated with targeting ligands to improve the targeting efciency of the designed nanocarriers. Few
individuals may develop antibodies against PEG, leading to reduced efcacy and
increased clearance of PEGylated nanocarriers. Developing strategies to overcome
immune responses and minimize PEG-related immunogenicity is an active area of
research (McSweeney et al. 2019). Despite the challenges associated with the
PEGylation technique, it remains a most lucrative area of research endeavors related
to drug delivery. Researchers are exploring innovative PEGylation methods, such as
site-specic or controlled PEGylation, which allow for precise control over the
location and density of PEG chains. These techniques aim to optimize the benets
of PEGylation while minimizing its potential drawbacks. Current developments in
the formulation of PEGylated nanocarriers focus on designing nanocarriers with
integrated functionalities beyond PEGylation. These may include incorporating targeting ligands, stimuli-responsive components, or imaging agents, thereby
188
A. Tiwari et al.
expanding the capabilities of nanocarriers for personalized and targeted therapy
(Ekladious etal. 2019).
Researchers are investigating alternative polymers or coatings that can provide
similar benets to PEGylation while addressing some of its challenges. These
include zwitterionic polymers, biomimetic coatings, or self-assembled monolayers,
which offer improved stability, reduced immunogenicity, and enhanced targeting
capabilities (Amoozgar and Yeo 2012). The future of nanocarrier-based drug delivery lies in combination therapies, where multiple therapeutic agents, such as drugs,
siRNA, or immunotherapies, are co-delivered using PEGylated nanocarriers. This
approach enables synergistic effects and improved treatment outcomes (Zhang etal.
2016b). Furthermore, with advancements in nanotechnology and PEGylation tech-
niques, the future of nanocarriers lies in personalized medicine. Tailoring nanocarriers to specic patient proles, disease characteristics, and therapeutic requirements
holds excellent potential for improving treatment efcacy and minimizing side
effects (Sakamoto etal. 2010).
While challenges exist, the eld of PEGylation and nanocarrier-based drug
delivery continues to evolve rapidly. With ongoing research, innovative techniques,
and a better understanding of nanocarrier behavior, the future looks promising for
overcoming current challenges and harnessing the full potential of PEGylated nanocarriers in clinical applications.
6.8 Conclusion
Nanocarriers are lucrative drug delivery vehicles, considering the unique advantages they offer. However, the immunogenicity concerns associated with nanocarriers constitute a signicant obstacle in their applications. Various surface modication
strategies have been explored to tackle the immune recognition of nanocarriers. One
of the most prominent approaches is surface modication of nanocarriers with PEG,
also known as PEGylation. The PEGylation has been regarded as a widely utilized
strategy to improve the performance of nanocarriers in drug delivery. It offers benets such as enhanced stability, prolonged circulation time, improved biocompatibility, and reduced immunogenicity.
Research in PEGylation continues to advance, exploring alternative coatings,
site-specic PEGylation, controlled release systems, immunogenicity mitigation,
combination therapies, advanced characterization techniques, and standardization.
These future directions aim to overcome the limitations of PEGylation, expand its
applications, optimize its performance, and ensure its safe and effective translation
into clinical use. As research progresses, it is expected that PEGylation-based technologies will continue to play a signicant role in drug delivery, biotechnology, and
diagnostics. Through ongoing efforts and advancements, the eld of PEGylation
holds promise for addressing current challenges and further improving the effectiveness and safety of nanocarriers in various therapeutic applications.
6 PEGylation asaTool toAlter Immunological Properties ofNanocarriers
189
References
Almeida AJ, Souto E (2007) Solid lipid nanoparticles as a drug delivery system for peptides and
proteins. Adv Drug Deliv Rev 59:478–490
Amoozgar Z, Yeo Y (2012) Recent advances in stealth coating of nanoparticle drug delivery sys-
tems. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:219–233
Anaya J-M, Shoenfeld Y, Rojas-Villarraga A, Levy R, Cervera R (2013) Autoimmunity: from
bench to bedside. El Rosario University Press, Bogota
Baker MP, Reynolds HM, Lumicisi B, Bryson CJ (2010) Immunogenicity of protein therapeutics:
the key causes, consequences and challenges. Self Nonself 1:314–322
Bellido E, Hidalgo T, Lozano MV, Guillevic M, Simón-Vázquez R, Santander-Ortega MJ,
González-Fernández Á, Serre C, Alonso MJ, Horcajada P (2015) Heparin-engineered meso-
porous iron metal-organic framework nanoparticles: toward stealth drug nanocarriers. Adv
Healthc Mater 4:1246–1257
Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene
glycol)-protein conjugates. Adv Drug Deliv Rev 55:1261–1277
Castro F, Pinto ML, Silva AM, Pereira CL, Teixeira GQ, Gomez-Lazaro M, Santos SG, Barbosa
MA, Gonçalves RM, Oliveira MJ (2017) Pro-inammatory chitosan/poly(γ-glutamic acid)
nanoparticles modulate human antigen-presenting cells phenotype and revert their pro-invasive
capacity. Acta Biomater 63:96–109
Chaplin DD (2010) Overview of the immune response. J Allergy Clin Immunol 125:S3–S23
Cheng Z, Li M, Dey R, Chen Y (2021) Nanomaterials for cancer therapy: current progress and
perspectives. J Hematol Oncol 14:85
Cooper D, Eleftherianos I (2017) Memory and specicity in the insect immune system: current
perspectives and future challenges. Front Immunol 8:539
Crawford L, Rosch J, Putnam D (2016) Concepts, technologies, and practices for drug delivery
past the blood–brain barrier to the central nervous system. J Control Release 240:251–266
De Groot MC, Van Zwieten-Boot BJ, Van Grootheest AC (2004) [Severe adverse reactions after
the use of Sulphur hexauoride (SonoVue) as an ultrasonographic contrast agent]. Ned Tijdschr
Geneeskd 148: 1887–1888
Debele TA, Yeh CF, Su WP (2020) Cancer immunotherapy and application of nanoparticles in
cancers immunotherapy as the delivery of immunotherapeutic agents and as the immunomodu-
lators. Cancers (Basel) 12:3773
Den Haan JMM, Arens R, Van Zelm MC (2014) The activation of the adaptive immune system:
cross-talk between antigen-presenting cells, T cells and B cells. Immunol Lett 162:103–112
Din FU, Aman W, Ullah I, Qureshi OS, Mustapha O, Shaque S, Zeb A (2017) Effective use of
nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine
12:7291–7309
Dobrovolskaia MA, McNeil SE (2007) Immunological properties of engineered nanomaterials.
Nat Nanotechnol 2:469–478
Donahue ND, Acar H, Wilhelm S (2019) Concepts of nanoparticle cellular uptake, intracellular
trafcking, and kinetics in nanomedicine. Adv Drug Deliv Rev 143:68–96
Du B, Jiang X, Huang Y, Li S, Lin JC, Yu M, Zheng J (2020) Tailoring kidney transport of organic
dyes with low-molecular-weight PEGylation. Bioconjug Chem 31:241–247
Duan X, Li Y (2013) Physicochemical characteristics of nanoparticles affect circulation, biodistri-
bution, cellular internalization, and trafcking. Small 9:1521–1532
Ebner A, Wildling L, Kamruzzahan ASM, Rankl C, Wruss J, Hahn CD, Hölzl M, Zhu R, Kienberger
F, Blaas D, Hinterdorfer P, Gruber HJ (2007) A new, simple method for linking of antibodies to
atomic force microscopy tips. Bioconjug Chem 18:1176–1184
Ekladious I, Colson YL, Grinstaff MW (2019) Polymer–drug conjugate therapeutics: advances,
insights and prospects. Nat Rev Drug Discov 18:273–294
Fernandes AI, Gregoriadis G (2001) The effect of polysialylation on the immunogenicity and anti-
genicity of asparaginase: implication in its pharmacokinetics. Int J Pharm 217:215–224
190
Fontana A, Spolaore B, Mero A, Veronese FM (2008) Site-specic modication and PEGylation of
pharmaceutical proteins mediated by transglutaminase. Adv Drug Deliv Rev 60:13–28
Fu D, Wang Z, Tu Y, Peng F (2021) Interactions between biomedical micro-/nano-motors and the
immune molecules, immune cells, and the immune system: challenges and opportunities. Adv
Healthc Mater 10:2001788
Fulton MD, Najahi-Missaoui W (2023) Liposomes in cancer therapy: how did we start and where
are we now. Int J Mol Sci 24:6615
Gamucci O, Bertero A, Gagliardi M, Bardi G (2014) Biomedical nanoparticles: overview of their
surface immune-compatibility. Coatings 4:139–159
Gulati NM, Pitek AS, Steinmetz NF, Stewart PL (2017) Cryo-electron tomography investigation
of serum albumin-camouaged tobacco mosaic virus nanoparticles. Nanoscale 9:3408–3415
Gulati NM, Pitek AS, Czapar AE, Stewart PL, Steinmetz NF (2018) The invivo fates of plant
viral nanoparticles camouaged using self-proteins: overcoming immune recognition. J Mater
Chem B 6:2204–2216
Gupta V, Bhavanasi S, Quadir M, Singh K, Ghosh G, Vasamreddy K, Ghosh A, Siahaan TJ,
Banerjee S, Banerjee SK (2019) Protein PEGylation for cancer therapy: bench to bedside. J
Cell Commun Signal 13:319–330
Hadjesfandiari N, Parambath A (2018) Stealth coatings for nanoparticles: polyethylene gly-
col alternatives. In: Engineering of biomaterials for drug delivery systems. Woodhead
Publishing, Sawston
Harris JM, Martin NE, Modi M (2001) Pegylation: a novel process for modifying pharmacokinet-
ics. Clin Pharmacokinet 40:539–551
Hatakeyama H, Akita H, Harashima H (2011) 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 63:152–160
Howard MD, Jay M, Dziubla TD, Lu X (2008) PEGylation of nanocarrier drug delivery systems:
state of the art. J Biomed Nanotechnol 4:133–148
Hu C-MJ, Zhang L, Aryal S, Cheung C, Fang RH, Zhang L (2011) Erythrocyte membrane-
camouaged polymeric nanoparticles as a biomimetic delivery platform. Proc Natl Acad Sci
U S A 108:10980–10985
Hu C-MJ, Fang RH, Wang K-C, Luk BT, Thamphiwatana S, Dehaini D, Nguyen P, Angsantikul
P, Wen CH, Kroll AV, Carpenter C, Ramesh M, Qu V, Patel SH, Zhu J, Shi W, Hofman FM,
Chen TC, Gao W, Zhang K, Chien S, Zhang L (2015) Nanoparticle biointerfacing by platelet
membrane cloaking. Nature 526:118–121
Jia Y, Li J (2015) Molecular assembly of Schiff Base interactions: construction and application.
Chem Rev 115:1597–1621
Kolate A, Baradia D, Patil S, Vhora I, Kore G, Misra A (2014) PEG—versatile conjugating ligand
for drugs and drug delivery systems. J Control Release 192:67–81
Kozma GT, Shimizu T, Ishida T, Szebeni J (2020) Anti-PEG antibodies: properties, formation, test-
ing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals. Adv Drug
Deliv Rev 154–155:163–175
Le Dévédec F, Strandman S, Hildgen P, Leclair G, Zhu XX (2013) PEGylated bile acids for use
in drug delivery systems: enhanced solubility and bioavailability of itraconazole. Mol Pharm
10:3057–3066
Lee JH, Yeo Y (2015) Controlled drug release from pharmaceutical nanocarriers. Chem Eng Sci
125:75–84
Li B, Wang F, Gui L, He Q, Yao Y, Chen H (2018) The potential of biomimetic nanoparticles for
tumor-targeted drug delivery. Nanomedicine (Lond) 13:2099–2118
Liu Y, Hardie J, Zhang X, Rotello VM (2017) Effects of engineered nanoparticles on the innate
immune system. Semin Immunol 34:25–32
Lombardo D, Kiselev MA, Caccamo MT (2019) Smart nanoparticles for drug delivery applica-
tion: development of versatile nanocarrier platforms in biotechnology and nanomedicine. J
Nanomater 2019:3702518
A. Tiwari et al.
6 PEGylation asaTool toAlter Immunological Properties ofNanocarriers
McSweeney MD, Price LSL, Wessler T, Ciociola EC, Herity LB, Piscitelli JA, Dewalle AC, Harris
TN, Chan AKP, Saw RS, Hu P, Jennette JC, Forest MG, Cao Y, Montgomery SA, Zamboni
WC, Lai SK (2019) Overcoming anti-PEG antibody mediated accelerated blood clearance of
PEGylated liposomes by pre-infusion with high molecular weight free PEG.J Control Release
311–312:138–146
Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R (2021) Engineering
precision nanoparticles for drug delivery. Nat Rev Drug Discov 20:101–124
Mohamed NA, Marei I, Crovella S, Abou-Saleh H (2022) Recent developments in nanomaterials-
based drug delivery and upgrading treatment of cardiovascular diseases. Int J Mol Sci 23:1404
Moses JE, Moorhouse AD (2007) The growing applications of click chemistry. Chem Soc Rev
36:1249–1262
Naing A, Papadopoulos KP, Autio KA, Ott PA, Patel MR, Wong DJ, Falchook GS, Pant S,
Whiteside M, Rasco DR, Mumm JB, Chan IH, Bendell JC, Bauer TM, Colen RR, Hong DS,
Van Vlasselaer P, Tannir NM, Oft M, Infante JR (2016) Safety, antitumor activity, and immune
activation of pegylated recombinant human INTERLEUKIN-10 (AM0010) in patients with
advanced solid tumors. J Clin Oncol 34:3562–3569
Nowinski AK, White AD, Keefe AJ, Jiang S (2014) Biologically inspired stealth peptide-capped
gold nanoparticles. Langmuir 30:1864–1870
Parhi P, Mohanty C, Sahoo SK (2012) Nanotechnology-based combinational drug delivery: an
emerging approach for cancer therapy. Drug Discov Today 17:1044–1052
Parodi A, Quattrocchi N, Van De Ven AL, Chiappini C, Evangelopoulos M, Martinez JO, Brown
BS, Khaled SZ, Yazdi IK, Enzo MV, Isenhart L, Ferrari M, Tasciotti E (2013) Synthetic
nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like func-
tions. Nat Nanotechnol 8:61–68
Peer D, Florentin A, Margalit R (2003) Hyaluronan is a key component in cryoprotection and for-
mulation of targeted unilamellar liposomes. Biochim Biophys Acta 1612:76–82
Pérez-Pérez L, García-Gavín J, Piñeiro B, Zulaica A (2011) Biologic-induced urticaria due to
polysorbate 80: usefulness of prick test. Br J Dermatol 164:1119–1120
Perry JL, Reuter KG, Kai MP, Herlihy KP, Jones SW, Luft JC, Napier M, Bear JE, Desimone JM
(2012) PEGylated PRINT nanoparticles: the impact of PEG density on protein binding, macro-
phage association, biodistribution, and pharmacokinetics. Nano Lett 12:5304–5310
Piao J-G, Wang L, Gao F, You Y-Z, Xiong Y, Yang L (2014) Erythrocyte membrane is an alternative
coating to polyethylene glycol for prolonging the circulation lifetime of gold nanocages for
photothermal therapy. ACS Nano 8:10414–10425
Qiao Z-Y, Zhao W-J, Gao Y-J, Cong Y, Zhao L, Hu Z, Wang H (2017) Recongurable peptide
nanotherapeutics at tumor microenvironmental pH.ACS Appl Mater Interfaces 9:30426–30436
Qin M, Du G, Sun X (2020) Biomimetic cell-derived nanocarriers for modulating immune
responses. Biomater Sci 8:530–543
Rabanel JM, Hildgen P, Banquy X (2014) Assessment of PEG on polymeric particles surface, a
key step in drug carrier translation. J Control Release 185:71–87
Rawat M, Singh D, Saraf S, Saraf S (2006) Nanocarriers: promising vehicle for bioactive drugs.
Biol Pharm Bull 29:1790–1798
Rodriguez PL, Harada T, Christian DA, Pantano DA, Tsai RK, Discher DE (2013) Minimal “self”
peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science
339:971–975
Saito G, Swanson JA, Lee K-D (2003) Drug delivery strategy utilizing conjugation via reversible
disulde linkages: role and site of cellular reducing activities. Adv Drug Deliv Rev 55:199–215
Sakamoto JH, Van De Ven AL, Godin B, Blanco E, Serda RE, Grattoni A, Ziemys A, Bouamrani A,
Hu T, Ranganathan SI, De Rosa E, Martinez JO, Smid CA, Buchanan RM, Lee S-Y, Srinivasan
S, Landry M, Meyn A, Tasciotti E, Liu X, Decuzzi P, Ferrari M (2010) Enabling individualized
therapy through nanotechnology. Pharmacol Res 62:57–89
Schöttler S, Becker G, Winzen S, Steinbach T, Mohr K, Landfester K, Mailänder V, Wurm
FR (2016) Protein adsorption is required for stealth effect of poly(ethylene glycol)- and
poly(phosphoester)-coated nanocarriers. Nat Nanotechnol 11:372–377
191
192
Sellaturay P, Nasser S, Ewan P (2021) Polyethylene glycol-induced systemic allergic reactions
(Anaphylaxis). J Allergy Clin Immunol Pract 9:670–675
Shi D, Beasock D, Fessler A, Szebeni J, Ljubimova JY, Afonin KA, Dobrovolskaia MA (2022)
To PEGylate or not to PEGylate: immunological properties of nanomedicine’s most popular
component, polyethylene glycol and its alternatives. Adv Drug Deliv Rev 180:114079
Sinz A (2006) Chemical crosslinking and mass spectrometry to map three-dimensional protein
structures and protein-protein interactions. Mass Spectrom Rev 25:663–682
Su S, Kang PM (2020) Recent advances in nanocarrier-assisted therapeutics delivery systems.
Pharmaceutics 12:837
Suk JS, Xu Q, Kim N, Hanes J, Ensign LM (2016) PEGylation as a strategy for improving
nanoparticle-based drug and gene delivery. Adv Drug Deliv Rev 99:28–51
Sun Q, Zhou Z, Qiu N, Shen Y (2017) Rational design of cancer nanomedicine: nanoproperty
integration and synchronization. Adv Mater 29
Sung H-J, Luk A, Murthy NS, Liu E, Jois M, Joy A, Bushman J, Moghe PV, Kohn J (2010)
Poly(ethylene glycol) as a sensitive regulator of cell survival fate on polymeric biomaterials:
the interplay of cell adhesion and pro-oxidant signaling mechanisms. Soft Matter 6:5196–5205
Tang L, Azzi J, Kwon M, Mounayar M, Tong R, Yin Q, Moore R, Skartsis N, Fan TM, Abdi R,
Cheng J (2012) Immunosuppressive activity of size-controlled PEG-PLGA nanoparticles con-
taining encapsulated cyclosporine A.J Transplant 2012:896141
Thasneem YM, Sajeesh S, Sharma CP (2013) Glucosylated polymeric nanoparticles: a sweetened
approach against blood compatibility paradox. Colloids Surf B: Biointerfaces 108:337–344
Thomas SN, Van Der Vlies AJ, O’Neil CP, Reddy ST, Yu SS, Giorgio TD, Swartz MA, Hubbell
JA (2011) Engineering complement activation on polypropylene sulde vaccine nanoparticles.
Biomaterials 32:2194–2203
Tian Y, Gao Z, Wang N, Hu M, Ju Y, Li Q, Caruso F, Hao J, Cui J (2022) Engineering
poly(ethylene glycol) nanoparticles for accelerated blood clearance inhibition and targeted
drug delivery. J Am Chem Soc 144:18419–18428
Toole BP (2004) Hyaluronan: from extracellular glue to pericellular cue. Nat Rev Cancer 4:528–539
Totten JD, Wongpinyochit T, Carrola J, Duarte IF, Seib FP (2019) PEGylation-dependent met-
abolic rewiring of macrophages with silk broin nanoparticles. ACS Appl Mater Interfaces
11:14515–14525
Tsai CH, Wang PY, Lin IC, Huang H, Liu GS, Tseng CL (2018) Ocular drug delivery: role of
degradable polymeric nanocarriers for ophthalmic application. Int J Mol Sci 19:2830
Verhoef JJ, Carpenter JF, Anchordoquy TJ, Schellekens H (2014) Potential induction of anti-PEG
antibodies and complement activation toward PEGylated therapeutics. Drug Discov Today
19:1945–1952
Vllasaliu D, Fowler R, Stolnik S (2014) PEGylated nanomedicines: recent progress and remaining
concerns. Expert Opin Drug Deliv 11:139–154
Wen P, Ke W, Dirisala A, Toh K, Tanaka M, Li J (2023) Stealth and pseudo-stealth nanocarriers.
Adv Drug Deliv Rev 198:114895
Wildling L, Unterauer B, Zhu R, Rupprecht A, Haselgrübler T, Rankl C, Ebner A, Vater D,
Pollheimer P, Pohl EE, Hinterdorfer P, Gruber HJ (2011) Linking of sensor molecules with
amino groups to amino-functionalized AFM tips. Bioconjug Chem 22:1239–1248
Wilson DR, Zhang N, Silvers AL, Forstner MB, Bader RA (2014) Synthesis and evaluation of
cyclosporine A-loaded polysialic acid-polycaprolactone micelles for rheumatoid arthritis. Eur
J Pharm Sci 51:146–156
Xia W, Tao Z, Zhu B, Zhang W, Liu C, Chen S, Song M (2021) Targeted delivery of drugs and
genes using polymer nanocarriers for cancer therapy. Int J Mol Sci 22:2830
Zalba S, Ten Hagen TLM, Burgui C, Garrido MJ (2022) Stealth nanoparticles in oncology: facing
the PEG dilemma. J Control Release 351:22–36
Zalipsky S (1995) Functionalized poly(ethylene glycols) for preparation of biologically relevant
conjugates. Bioconjug Chem 6:150–165
A. Tiwari et al.
6 PEGylation asaTool toAlter Immunological Properties ofNanocarriers
Zarreen Simnani F, Singh D, Patel P, Choudhury A, Sinha A, Nandi A, Kumar Samal S, Verma
SK, Kumar Panda P (2023) Nanocarrier vaccine therapeutics for global infectious and chronic
diseases. Mater Today 66:371–408
Zhang P, Sun F, Liu S, Jiang S (2016a) Anti-PEG antibodies in the clinic: current issues and
beyond PEGylation. J Control Release 244:184–193
Zhang RX, Wong HL, Xue HY, Eoh JY, Wu XY (2016b) Nanomedicine of synergistic drug combi-
nations for cancer therapy—strategies and perspectives. J Control Release 240:489–503
Zheng X, Bao Y, Huang A, Yu L, Qin G (2023) Temperature dependence of thermophysical proper-
ties of polyethylene glycol in solid/liquid phase change region. J Chem Thermodyn 180:107022
Zolnik BS, González-Fernández AF, Sadrieh N, Dobrovolskaia MA (2010) Minireview: nanopar-
ticles and the immune system. Endocrinology 151:458–465
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PEGylated Nanocarrier asaPromising
Tool forSite-Specific Delivery
ofTherapeutics
SwetaAcharya, NiyatiLad, AniketNavale, SimranjitKaur,
AprameyaGaneshPrasad, andRakeshKumarTekade
Abstract
Nanocarrier systems have gained popularity for drug delivery and diagnostic
purposes, offering targeted and site-specic transport of highly efcacious medi-
cations. These systems connect biological and physical sciences, allowing for the
treatment of various diseases and disorders. They can avoid severe side effects,
improve target specicity, and reduce doses. Modifying carrier properties, such
as targeted delivery, regulated distribution, and shielding from biological milieus,
can further enhance their benets. Several targeted nanocarrier systems such as
nano-crystals, lipid nanoparticles (NPs), PEGylated polymeric nanocarriers,
nanobers, quantum dots, liposomes, dendrimers, micelles, protein-based
nanoparticles, and metal-based nanoparticles are well explored for their benets
over conventional drug delivery systems. This chapter specically highlights the
different types of PEGylated nanocarriers and their uses in targeted drug delivery.
7
Keywords
PEGylated nanocarriers · Liposomes · Cancer · Brain disorders · Pulmonary dis-
orders · Targeted delivery · EPR effect · RES system
S. Acharya · N. Lad · A. Navale · S. Kaur · R. K. Tekade (*)
National Institute of Pharmaceutical Education and Research (NIPER) Ahmedabad, An
Institute of National Importance, Government of India, Department of Pharmaceuticals,
Ministry of Chemicals and Fertilizers, Palaj, Opp. Air force stations, Gandhinagar,
Gujarat, India
A. G. Prasad
Department of Chemical and Biomolecular Engineering, Johns Hopkins University,
Baltimore, MD, USA
195
196
S. Acharya et al.
Abbreviations
Anti-hMAM Anti-human mammaglobin
BBB Blood brain barrier
Bcl-2 B-cell lymphoma-2
BPQDs Black phosphorus quantum dots
BSA Bovine serum albumin
CaP Calcium phosphate
CAT Catalase
ChNPs Chitosan nanoparticles
CNTs Carbon nanotubes
DDS Drug delivery systems
DMARDs Disease-modifying anti-rheumatic drugs
DMMA-P-DOX/LAP 2,3-Dimethylmaleic-anhydride-poly(ethylene glycol)-ε-
poly- -lysine-doxorubicin/lapatinib polymeric
DOPE 1,2-Dioleyl-sn-glycero-3-phosphoethanolamine
DOX Doxorubicin
DPI Dry powder inhaler
EAE Encephalomyelitis
EGFP Enhanced green uorescent protein
EGFR Epidermal growth factor receptor
EPR Enhanced permeability and retention
ERs Estrogen receptors
FA Folic acid
FMN Formononetin
GBM Glioblastoma multiforme
GCs Glucocorticoids
GEM Gemcitabine
GFLG Glycylphenylalanylleucylglycine
GO Graphene oxide
GOD Glucose oxidase
GSH Glutathione
HA Hyaluronic acid
Has Human serum albumin
HEL Hen egg-white lysozyme
HER2 Human epidermal growth factor receptor 2
HPMA Hydroxy propyl methacrylamide-methacid
IA Intra-articular
LRP Low-density lipoprotein receptor
mAbs Monoclonal antibodies
MCF-7 Michigan cancer foundation-7
Mcl-1 Myeloid cell leukemia-1
MMP Mitochondrial membrane potential
MWNTs Multi-walled carbon nanotubes
NCs Nanocarriers