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16 Beyond PEGylation “PEGylation andits Alternatives”
467
(c) Reduced protein adsorption on surfaces coated with pCBMA has been shown
in invivo investigations using animal models, leading to extended circulation
durations for drug carriers. This shows that the body tolerates pCBMA well
(Taylor etal. 2021).
According to studies on its toxicity, when manufactured correctly and delivered
in the proper doses, pCBMA does not demonstrate acute toxicity or adverse effects
on essential organs. However, like with any substance, negative consequences could
result from prolonged exposure or high doses. To avoid contamination, pCBMA
should be synthesized and handled in sterile circumstances. Any impurities added
during synthesis or handling can jeopardize the product’s safety prole. For each
unique drug delivery application, the pCBMA dosage and concentration should be
calculated. Appropriate dosage is essential to get the desired PEG-like effects while
lowering the risk of overexposure. It’s important to do thorough safety assessments
and research for each situation because the safety prole can vary depending on the
specic poly(zwitterion) and its application (Marcelino 2016).
Since poly(zwitterions) exhibit much stronger intramolecular interactions via
ionic binding than PEG, this could explain their high nonspecic protein resistance
capability mediated by higher charge density (Cao and Jiang 2012). Since synthetic
zwitterionic materials like poly(carboxybetaine) (pCB) and poly(sulfobetaine)
(pSB) (Fig.16.6) have strong hydration shells, they have been suggested as PEG
substitutes. This property imparts them with low immunogenicity while also making them more resistant to nonspecic protein fouling (Yang etal. 2009; Jiang and
Cao 2010). These polyelectrolytes’ excellent non-fouling properties are due to their
intense hydration, which is caused by electrostatic interactions between the ionic
functional groups and water molecules. This property is essential in the construction
of polymer protein conjugates, self-assembled nanoparticles, and vesicles.
Poly(zwitterions) are very hydrophilic and poorly soluble in most nonpolar solvents, in contrast to PEG (Cao et al. 2011; Keefe and Jiang 2012; Jiang and
Cao 2010).
Here’s how poly(zwitterions) are used for PEGylation and their applications in
drug delivery systems. Like PEGylation, polyzwitterion conjugation can improve
the pharmacokinetics of drugs and therapeutic molecules. They can, therefore,
extend the drug’s circulation time in the bloodstream, increasing its bioavailability.
Poly(zwitterions), due to their neutral charge and biocompatible properties, can
reduce the immunogenic response of the drug. This is important for enhancing the
safety prole of biopharmaceuticals. It can create a hydrophilic surface that resists
protein adsorption, which helps prevent opsonization. Opsonization can mark drug
delivery systems for removal by the immune system, so minimizing this process
improves drug delivery efciency (Laschewsky 2014). Poly(zwitterions) can be
used as biocompatible coatings on medical implants and devices to reduce the risk
of inammation and infection. Their biocompatibility and resistance to protein
adsorption make them ideal for improving the safety and performance of medical
implants. Additionally, poly(zwitterions) can be used to functionalize nanoparticles
or liposomes for drug delivery to tumor sites. The stealthy nature of the polymer can
468
S. Mohanta et al.
help evade the immune system and enhance tumor-specic drug delivery (Zheng
etal. 2017), potentially improving the efcacy of cancer treatments. The use of
polyzwitterions for PEGylation offers a versatile and biocompatible alternative to
traditional PEGylation, and it continues to be an area of active research in the development of advanced drug delivery systems and biomaterials. Although
poly(zwitterions) have substantial advantages, more research may be required to
establish them as an alternative to PEG polymers.
16.5.2 Poly(Glycerols)
Poly(glycerols) (PGs) have recently emerged as a potential alternative to PEG in a
variety of pharmaceutical applications. Frey and colleagues rst synthesized PGs,
and their applications werefurther explored and expanded by the research groups of
Haag and Brooks (Imran Ul-Haq etal. 2012; Kainthan etal. 2006; Kurniasih etal.
2015). Poly(glycerols) of various molecular weights have been synthesized in a
highly regulated manner using anionic ring-opening polymerization of glycidol
(Kainthan etal. 2006; Kurniasih etal. 2015; Sunder etal. 1999). Poly(glycerols) are
hyperbranched, compact structures with high hydrophilicity and biocompatibility.
Their low intrinsic viscosity in water and a structure amenable to multifunctionalization make them attractive alternatives to PEG.
Poly(glycerols) are extremely hydrophilic polymers with a high attraction for
water. This characteristic avoids protein and other biomolecule adsorption on the
surface of drug carriers or biomaterials, resulting in a hydrophilic and “stealthy”
layer. This, like PEG, decreases opsonization (the immune system’s identication
and clearance of foreign elements) and increases circulation times. Poly(glycerols)
are biocompatible and are less prone to elicit an immunological response. They lack
the immunogenicity that certain other materials may have, which is critical for
improving the safety of drug delivery systems and biomaterials. Poly(glycerol)
characteristics, such as molecular weight and architecture, can be tuned to tailor
their performance to specic applications. This adaptability enables researchers to
optimize drug delivery systems for various therapeutic objectives (Sunder
etal. 1999).
A variety of chemical processes can be used to conjugate poly(glycerols) to drug
carriers or nanoparticles. The specic chemistry used is determined by the functional groups present on the polymer and the drug carrier’s surface. The following
is a general overview of how poly(glycerols) can be conjugated: both poly(glycerol)
and the drug carrier must be functionalized with reactive groups. Hydroxyl (-OH),
amino (-NH2), and carboxyl (-COOH) groups are the typical functional groups
required for PG conjugation (Gheybi etal. 2018). Esterication, amide bond formation, and click chemistry are examples of common chemistries involved. Suppose
both the poly(glycerol) and the carrier have hydroxyl groups. In that case, they can
be conjugated by activating one with a coupling reagent (e.g., N-hydroxysuccinimide
or NHS) and reacting it with the other, which has compatible functional groups
(Cao et al. 2016). In some circumstances, poly(glycerols) may be utilized for
16 Beyond PEGylation “PEGylation andits Alternatives”
469
surface modication rather than direct conjugation. In this case, the polymer forms
a protective layer over the drug carrier or nanoparticle, resulting in a biocompatible,
stealthy surface.
The poly(glycerols) employed and the chemistry used for conjugation will be
determined by the application and desired attributes of the drug delivery system.
Due to their high purity and quality, poly(glycerols) are essential in drug delivery
systems and biomaterial applications. They must undergo biocompatibility testing
to assess their safety and interactions with biological systems. Chemical compatibility with other drug delivery system components is crucial, and contamination
control is essential to assure sterility. The optimal dosage and concentration of
poly(glycerols) should be determined, as excessive amounts may not improve the
PEG-like effect and may result in unnecessary exposure (Abbina etal. 2017).
Like poly(glycerol), PEGylated liposomes are a commonly studied and utilized
drug delivery system. These liposomes have a poly(glycerol) PEG layer on their
surface, which provides improved biocompatibility and stability. Poly(glycerol)
PEGylated liposomes have shown high biocompatibility, low cytotoxicity, minimal
immune response, and extended circulation times in the bloodstream. They do not
exhibit acute toxicity, but exposure to high concentrations may cause adverse effects
(Liang etal. 2010). They should be prepared and handled under sterile conditions to
prevent contamination. The optimal dosage and concentration for each drug delivery application should be determined, achieving desired PEG-like effects while
minimizing overexposure risk.
Kizhakkedathu’s research group has created biodegradable PGs by including
acid-sensitive ketal moieties. They were able to establish high degradation proles,
which aided in the reduction of hepatic and renal biodistributions. They found no
appreciable PG buildup during the 1–7day injection period. Because of these outstanding features, PGs may be promising candidates for developing long-circulating
multifunctional drug delivery systems. There are a few PG-based investigational
therapeutics that are undergoing clinical testing at various stages (Shenoi etal.
2016, 2012; Yu etal. 2012).
16.5.3 Poly(Amino Acids)
Poly(amino acids) have been extensively researched as structural and biofunctional
structural materials for applications in drug delivery, and they are typically synthesized via condensation polymerization of amino acid monomers (Romberg etal.
2007; Obst and Steinbüchel 2004; Sun etal. 2011). Poly(amino acids) are a poten-
tial alternative to PEG due to their charged side chains, biodegradability, biocompatibility, and minimal toxicity. Though they are hydrophilic in nature, they can be
easily functionalized into the polymer backbone with groups like alcohol, amine,
and thiol (Nishikawa and Ogawa 2004) (Fig.16.9).
Poly(amino acids) exhibit a “PEG-like effect” in drug delivery and biomaterial
applications, improving pharmacokinetics and biocompatibility. They are hydrophilic, preventing protein adsorption through a “stealthy” layer, and biocompatible,
470
Fig. 16.9 Chemical
structure of poly(amino
acid)s
S. Mohanta et al.
reducing immune responses. They are also customizable, allowing researchers to
optimize drug delivery systems for various therapeutic goals. This effect is attributed to their strong afnity for water, biocompatibility, and ability to be tailored to
specic applications.
Poly(amino acids) can be conjugated to drug carriers or nanoparticles through
various chemical reactions, depending on the functional groups on the polymer and
the drug carrier’s surface. Typical functional groups include amino (-NH2), carboxyl (-COOH), and thiol (-SH). The specic chemistry used for conjugation
depends on the functional groups involved, such as amide bond formation, click
chemistry, and thiol-disulde exchange reactions. For example, suppose both the
poly(amino acid) and carrier have carboxyl groups. In that case, they can be conjugated by activating one with a coupling reagent like N-hydroxysuccinimide (NHS)
and reacting with the other with amino groups. Poly(amino acids) can also be used
for surface modication, creating a protective layer around the drug carrier or
nanoparticle. The choice of poly(amino acids) and the specic chemistry used for
conjugation depends on the application and desired properties of the drug delivery
system (Yang etal. 2006).
PEGylated nanoparticles are a widely used drug delivery system with a
poly(glutamic acid) PEG layer on their surface, providing enhanced biocompatibility and stability. Studies have shown that these nanoparticles exhibit low cytotoxicity and minimal immune response, and in vivo studies in animal models show
extended circulation times in the bloodstream. Toxicity studies show that these
nanoparticles do not exhibit acute toxicity, but extensive exposure to high concentrations may lead to adverse effects. They should be prepared and handled under
sterile conditions to prevent contamination. The optimal dosage and concentration
should be determined for each specic drug delivery application, achieving desired
PEG-like effects while minimizing overexposure risk. Safety proles can vary
depending on the particular poly(amino acid) used and its application, and detailed
safety assessments and studies are essential (Mccormick-Thomson etal. 1989).
Poly(amino acids) are used in a variety of biopharmaceutical and cosmetic applications, as well as for environmental and agricultural purposes (Sun etal. 2011; Li
and Wallace 2008; Shima and Sakai 1977). There are many natural poly(amino
acids) such as cyanophycin, poly(alanine), poly(-glutamic acid), and poly(lysine),
as well as synthetic poly(amino acids) like poly(hydroxyethyl-L-glutamine) and
poly(hydroxyethyl-L-asparagine) have been investigated for various applications.
Phase III clinical studies have also investigated poly(L-glutamic acid) (PGs). PGs
16 Beyond PEGylation “PEGylation andits Alternatives”
471
nd other applications as well, such as their use as a food thickening agent, in fertilizers, and in cosmetics as a wetting agent. Even though poly(amino acids) have
made great advances in recent years, they still have aws, particularly synthetic
restrictions (Romberg etal. 2007; Yang etal. 2010; Shih etal. 2004; Melancon and
Li 2011).
16.5.4 Poly(Oxazolines)
Poly(oxazolines) (POX) are another intriguing class of bioinspired polymers that
have been investigated for various pharmaceutical applications. POX is biocompatible, can prevent rapid clearance, and control protein adsorption. They are neutrally
charged and exhibit high stability and solubility in both polar and nonpolar solvents.
POX also comes in a variety of architectural and chemical congurations. They are
easily synthesized using the controlled cationic ring-opening polymerization of
cyclic oxazolines (Guillerm etal. 2012). In many cases, the physicochemical features of POX have been reported to be equivalent to those of PEG, and they may be
easily modied by inserting various functional groups on the monomer’s oxazoline
ring and altering the monomer concentration (Guillerm etal. 2012; Lava etal. 2015;
Hoogenboom 2009) (Fig.16.10).
Poly(oxazolines) are polymers that mimic the characteristics of poly(ethylene
glycol) (PEG), exhibiting a PEG-like effect in drug delivery and biomaterials. They
have hydrophilicity, creating a protective layer on drug delivery systems or biomaterials, minimizing protein adsorption, and immune system recognition. They also
produce a stealth effect by reducing interactions with serum proteins and cells,
ensuring the stability of the drug delivery system. Their biocompatibility reduces
adverse reactions and improves safety.
Poly(oxazolines) can be conjugated to various molecules, surfaces, or particles
through various chemical reactions, depending on the functional groups of the polymer and the substrate. These reactions can be initiated during synthesis or postpolymerization. Poly(oxazolines) can be conjugated to a substrate using amidation,
thiol-ene click reactions, or carbodiimide-mediated coupling. If both the polymer
and substrate have reactive functional groups, they can be linked to form a stable
covalent bond. Poly(oxazolines) can also be used to modify nanoparticles, micelles,
or other drug delivery systems, providing a stealthy and biocompatible surface
Fig. 16.10 Chemical
structure of poly(2-ethyl-2oxazoline), PEOXA, a
poly(oxazoline)
472
S. Mohanta et al.
(Harris etal. 2019). The choice of poly(oxazolines) and chemistry for conjugation
depends on the application and desired properties of the drug delivery system.
Poly(oxazolines) are promising alternatives to PEG, offering similar benets in
drug delivery and biomaterial applications while providing opportunities for netuning their properties to meet specic biomedical needs (Sedlacek and
Hoogenboom 2020).
Due to their high purity and quality, poly(oxazolines) are used in drug delivery systems and biomaterial applications. They must undergo biocompatibility testing to
assess their safety and interactions with biological systems. Chemical compatibility is
also crucial, as incompatibilities can lead to degradation, reduced drug efcacy, or
undesired by-products. Sterility and contamination control are essential to prevent contamination during the synthesis, handling, and storage of poly(oxazolines). The optimal dosage and concentration of poly(oxazolines) in drug delivery systems should be
determined, as excessive amounts may not improve the PEG-like effect and may result
in unnecessary exposure. These precautions ensure the safety and performance of the
materials used in these applications (Kronek etal. 2013).
Poly(2-methyl-2-oxazoline) (PMeOx) is a poly(oxazoline) polymer used to
modify micelles for drug delivery applications. These micelles have shown high
biocompatibility, minimal cytotoxicity, and low immunogenicity in invitro studies.
In vivo studies in animal models indicate that they extend circulation in the blood,
reducing protein adsorption and opsonization, enhancing safety. Toxicity studies
show that PMeOx-modied micelles do not exhibit acute toxicity, but excessive
exposure may lead to adverse effects. Sterility is crucial for handling PMeOxmodied micelles (Drago etal. 2021). The optimal dosage and concentration should
be determined for each specic drug delivery application, achieving PEG-like
effects while minimizing overexposure risk. Safety proles can vary depending on
the poly(oxazolines) used and the application, thereby necessitating detailed safety
assessments and studies.
As an alternative to PEGylation, the concept of POXylation has been warmly
embraced. Various POX polymers, particularly poly(2-ethyl-2-oxazoline) (PEtOx)
and poly(2-methyl-2-oxazoline) (PMeOx), have been studied for self-assembly
applications mediated by physical and chemical coupling techniques. They have
also been explored as a stealth polymer for therapeutics and antimicrobial agent
delivery. As they are thermo-sensitive, they have also been applied in responsive
polymers and hydrogels (Viegas etal. 2011; Hoogenboom 2009; Seeliger etal. 1966).
16.5.5 Poly(Acrylamides) andAllied Other Systems
Several research groups have made substantial contributions towards developing
vinyl-based polymers as a viable substitute for PEG over the last 50 years.
Polyacrylamide, a derivative of acrylamide, has been utilized for various applications, primarily as a support matrix for electrophoresis (Milla etal. 2012; Nag and
Awasthi 2013). Nonionic polyacrylamides can be linear, branched, or substituted.
Some of the properties that make polyacrylamide a promising candidate are its
16 Beyond PEGylation “PEGylation andits Alternatives”
473
biocompatibility, nontoxicity, cost-effectiveness, and stability over a wide pH range
(pH3–11), (Amoozgar and Yeo 2012; Kadajji and Betageri 2011; Nag and Awasthi
2013) (Fig.16.11).
Poly(acrylamides) exhibit a PEG-like effect due to their hydrophilicity and steric
hindrance, creating a protective layer on drug delivery systems or biomaterials. This
prevents protein adsorption, thereby enhancing drug bioavailability.
Poly(acrylamides) are biocompatible, reducing immune responses and adverse
reactions. Their properties can be adjusted to optimize performance for specic
applications, allowing researchers to ne-tune their performance.
Poly(acrylamides) can be conjugated to drug carriers or nanoparticles through
various chemical reactions, depending on the functional groups present on the polymer and the drug carrier’s surface. Functional groups like amino (-NH2), carboxyl
(-COOH), or thiol (-SH) can be introduced during synthesis or post-polymerization.
Chemical conjugation can occur through amidation, thiol-ene click reactions, and
carbodiimide-mediated coupling. If both polymers have reactive functional groups,
they can be linked to form a stable covalent bond. Poly(acrylamides) can also be
used to modify the surface of nanoparticles, micelles, or other drug delivery systems, providing a hydrophilic and biocompatible layer for enhanced stability and
circulation times (Liu etal. 2016a).
Poly(acrylamides) are essential materials in drug delivery systems and biomaterial applications, but they must be of high purity and quality to ensure safety and
performance. Biocompatibility testing is crucial to assess their safety and interactions with biological systems, including invitro and invivo studies. Chemical compatibility is essential to prevent degradation, reduced drug efcacy, or unwanted
by-products. Sterility and contamination control are imperative to prevent contamination during the synthesis, handling, and storage of poly(acrylamides). Dosage
optimization is crucial to determine the optimal dosage and concentration of
poly(acrylamides) in drug delivery systems, as excessive amounts may not improve
the PEG-like effect and may result in unnecessary exposure (Pathania etal. 2016).
Poly(acrylamide) hydrogels are used in tissue engineering due to their biocompatibility, low cytotoxicity, and compatibility with surrounding tissues. They do not
exhibit acute toxicity, but cross-linking and polymerization are crucial. Sterile handling is essential to prevent contamination. The optimal dosage and concentration
should be determined for each tissue engineering application to achieve desired
therapeutic effects without unnecessary exposure. The safety prole can vary
depending on the specic poly(acrylamides) used and the application (King and
Noss 1989).
Fig. 16.11 Chemical
structures of
poly(acrylamide)s: (a)
Polyacrylamide (PAM) and
(b) partially hydrolyzed
polyacrylamide (PHPA)
474
S. Mohanta et al.
Poly(acrylamides) are generally employed in hydrogels for applications in
implantable devices, protein separation, and delivery of protein and oligonucleotides. While polyacrylamide coating tends not to elicit an immune response, with
negligible cytotoxicity, there are reports (Smith and Oehme 1991; Caló and
Khutoryanskiy 2015) of its implants inducing an inammatory response. Another
signicant disadvantage of these materials is the monomer’s highly hazardous side
effects. These disadvantages limit polyacrylamides’ extensive use in biological
applications. Poly(N-(2-hydroxypropyl) methacrylamide) (PHPMA) is a fascinating acrylamide-based polymer, and its conjugates have been investigated in clinical
studies, particularly with chemotherapeutics (Kopeček and Kopečková 2010;
Ulbrich and Šubr 2010).
16.5.6 Poly(Vinylpyrrolidones)
Solubilizing chemicals tend to solubilize and enhance the bioavailability of several
formulations. Poly(vinylpyrrolidone) (PVP), povidone, is a commonly used excipient and binder in the pharmaceutical industry. Over the previous four decades, signicant advances have been made to commercialize PVP-based materials for a wide
range of applications (Francis etal. 1998; Hsiao and Huang 2005; Liu etal. 2013)
(Fig.16.12).
Poly(vinylpyrrolidones) are a class of polymers that can create a “PEG-like
effect” in drug delivery and biomaterial applications. This effect is similar to
poly(ethylene glycol) (PEG) and involves the hydrophilicity and steric hindrance of
poly(vinylpyrrolidones) to enhance the pharmacokinetics and biocompatibility of
drug delivery systems. This hydrophilicity prevents protein adsorption, opsonization, and immune recognition, allowing the drug delivery system to circulate in the
bloodstream for more extended periods, enhancing drug bioavailability.
Poly(vinylpyrrolidones) are generally biocompatible, reducing the risk of adverse
reactions. Additionally, the properties of poly(vinylpyrrolidones), such as molecular
weight, architecture, and functional groups, can be adjusted to optimize
Fig. 16.12 Chemical
structure of
poly(vinylpyrrolidone)
16 Beyond PEGylation “PEGylation andits Alternatives”
475
performance for specic applications, allowing researchers to ne-tune these properties to meet the requirements of the drug delivery system (Koczkur etal. 2015).
Poly(vinylpyrrolidones) can be conjugated to drug carriers or nanoparticles
through various chemical reactions, depending on the functional groups on the
polymer and the drug carrier’s surface. Functional groups like amino (-NH2), carboxyl (-COOH), or thiol (-SH) can be introduced during synthesis or postpolymerization. Chemical conjugation can occur through amidation, thiol-ene click
reactions, and carbodiimide-mediated coupling. If both polymers have reactive
functional groups, they can be linked to form a stable covalent bond.
Poly(vinylpyrrolidones) can also be used to modify the surface of nanoparticles,
micelles, or other drug delivery systems, providing a hydrophilic and biocompatible
layer that enhances stability and circulation times. The choice of poly(acrylamides)
and chemistry depends on the application and desired drug delivery system properties (Zelikin etal. 2007).
Poly(vinylpyrrolidone) (PVP) is a drug delivery system that requires strict quality control and biocompatibility testing. Its chemical compatibility with other drug
delivery components is crucial to prevent degradation or reduced efcacy. Sterility
and contamination control are essential to prevent contamination. The optimal dosage and concentration of PVP should be determined to ensure the best PEG-like
effect and avoid unnecessary exposure (Yu etal. 2009).
PVP is a widely used material for drug delivery. Studies have shown that PVPmodied liposomes have low cytotoxicity and extended circulation times in the
bloodstream, enhancing drug delivery safety and efcacy. Toxicity studies reveal
that PVP-modied liposomes do not exhibit acute toxicity, but thorough preparation
and purication are crucial. Sterility is also essential to prevent contamination. The
optimal dosage and concentration of PVP-modied liposomes should be determined for each specic drug delivery application, achieving PEG-like effects while
minimizing overexposure risks (Schwarz 2018). The safety prole varies depending
on the PVP used and the application, and detailed safety assessments and studies are
essential.
PVP’s strong hydration shell aids in inhibiting immune system interaction and
enabling enhanced blood circulation and minimal protein adsorption. PVP degrades
slower than PEG when exposed to ultraviolet light. PVP-based compounds are used
in several industries with applications in adhesives, dyes, coatings, photoresists,
photography, textiles, bers and textiles, disinfectants, and food additives (Liu etal.
2013). PVP can be synthesized in various molecular weights by free and controlled
radical polymerization methods. As with polyacrylamides, the free monomer in
PVP should be entirely eliminated because it is highly carcinogenic. Although
PVP’s biocompatibility is promising, it suffers from issues such as uncertain immunological behavior and organ accumulations above excretion limitations (Le Garrec
etal. 2002; Torchilin 1998; Zelikin etal. 2007).
476
Fig. 16.13 Chemical
structure of Poly
[oligo(ethylene glycol)
methyl ether methacrylate]
(POEGMA)
S. Mohanta et al.
16.5.7 Poly[Oligo(Ethylene Glycol) Methyl Ether
Methacrylate] (POEGMA)
POEGMA is a water-soluble polymer composed of numerous ethylene glycol (EG)
chains grafted over a hydrophobic methyl methacrylate framework (Lutz 2008).
The hydrophilicity and biocompatibility of methacrylate polymers are linked to oligoethylene glycol (EG) chain grafting, which makes them appropriate for application in biomedicine. Lutz’s and coworkers further demonstrated thermo-responsive
behavior and antifouling properties of POEGMA (Lutz etal. 2007). POEGMA was
developed as an alternative to linear PEG by modifying PEG into a bottlebrush
design to address PEG-associated ABC (Joh etal. 2019). POEGMA, which was
synthesized, has a 3D hyperbranched structure with numerous side chains of EG
moieties and effective stealth characteristics (Pires-Oliveira etal. 2020; Hucknall
etal. 2009) (Fig.16.13).
POEGMA is often conjugated with various therapeutic agents, such as peptides
(Qi etal. 2016), proteins (Liu etal. 2014), nanoparticles (Nastyshyn etal. 2020),
nanocrystals (Roberts etal. 2020), and micelles (Skandalis and Pispas 2017; Zhao
etal. 2016). This can prevent immunogenicity and improve the circulation half-life
of these therapeutics, resulting in better efcacy. Moreover, this hydrophilic polymer also has wider applications in the eld of gene delivery (Üzgün etal. 2010),
tumor targeting (Sano etal. 2022), and tissue engineering (Harrison etal. 2015).
16.5.8 Polypeptides
Polypeptides have various advantages over PEG (polyethylene glycol) and may be
a better choice in some cases. Here are some of the reasons why polypeptides are
employed as PEG substitutes:
(a) Polypeptides, made up of amino acids, are biodegradable and can be broken
down by the body’s enzymatic processes, making them suitable for applications
where long-term retention is not desired.
(b) They are also minimally immunogenic, as they are based on naturally occurring
sequences in the human body, making them suitable for immunogenicity concerns. Polypeptides can be designed with specic targeting sequences, allowing
for more precise drug delivery (González-Aramundiz etal. 2012).