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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5894_Библиотеки_им_академика_М_И_Перельмана.pdf
1 PEGylated Pharmaceutical Nanocarriers
7
guarantees stabilization in an aqueous medium. It gives it an advantage over surfactant micelles, mainly when diluted in blood, the CMC falls, and the drug precipitates (Luan etal. 2019).
1.1.4 PEG Toxicity inPEGlyted Products
Many articles, most recently that of Fruijtier-Pölloth (2005), have thoroughly studied and evaluated the toxicity of PEG.However, oral administration has been used
in most PEG toxicity research. Pharmacokinetic results unequivocally show that
oral absorption reduces as PEG molecular weight rises. Therefore, it is impossible
to distinguish between toxicity and absorption changes using the data. PEGs delivered intravenously, subcutaneously, or intraperitoneally enable direct comparison of
the toxicological exposure relationship. Most PEG toxicological investigations have
used ‘regular’ PEG, which has both hydroxyl groups present. When observed, toxicity is typically linked to the kidneys and can cause extreme structural vacuolation
of the proximal renal tubules (Ciolacu etal. 2020). In general, these compounds
have little to no toxicity. However, it is thought that data from the rat and rabbit are
likely comparable, particularly as renal excretion of PEG is thought to be the primary clearance method in both situations. It is unclear what causes PEG to be toxic
to the kidneys (Karabasz etal. 2019).
Prior investigations on toxicity utilizing polymeric micelles made of PEG-P(Asp
(Bzl) block copolymers of poly(ethylene glycol) and poly(aspartate) block were
conducted using rats of the Donryu strain. All-trans retinoic acid and camptothecin
were synthetic retinoids transported via a block copolymer. Researchers used rats of
the Donryu strain to investigate the associated toxicities. They administered intravenously delivered injections ve times (low dose) or 200mg/kg (high dose) daily.
The brain, thymus, lymph node, heart, lungs, liver, spleen, and kidneys underwent
histological examinations to determine the weights of the principal organs and the
change in body weight at the time of sacrice.
However, knowing a few potential issues with PEG as a medication carrier is
vital. The faster blood clearance caused by PEGylation carriers is the rst issue.
Numerous investigations have discovered that while a PEGylated carrier’s initial
dosage resulted in extended circulation invivo, the subsequent treatment led to fast
clearance. This was explained by the development of anti-PEG antibodies, which
might have sped up the removal of the nanocarriers. Hypersensitivity, caused by
PEG injection inducing an immune response invivo, would be a second issue. The
immune system’s nonspecic and specic recognition of the PEG (by anti-PEG
antibodies) has been blamed for the reaction. The nonbiodegradability of PEG presents a third issue; additional research is still required to determine whether PEG is
eliminated from the body and whether any negative consequences may result from
potential PEG accumulation (Padín-González etal. 2022). Pharmaceutical uses of
PEG is shown in (Fig.1.1) and clinically approved PEG products are listed in
(Table1.1).
8
Fig. 1.1 Pharmaceutical uses of PEG
P. Pingale et al.
Table 1.1 Clinically approved PEG products
Brand name
Adagen Enzon Severe combined
Cimzia Nektar UCB
Daxil/
calyx
Macugen Pzer Neovascular age-related
Mircera Roche Anemia associated with
Neulasta Amgen Chemotherapy-induced
Omontys Affymax/Takeda
Oncaspar Enzon Acute lymphoblastic
Company Indication
immunodeciency disease
(SCID)
Rheumatoid arthritis and
Pharma
Ortho Biotech/
Schering-Plough
Pharmaceuticals
Crohn’s disease
Cancer The PEGylated liposome of
macular degeneration
chronic kidney disease
neutropenia
Anemia associated with
chronic kidney disease
leukemia
Comment
PECylated adenosine
deaminase
PEGylated Fab’ fragment of
a humanized TNF inhibitor
monoclonal antibody
doxorubicin
Pegylated anti-vascular
endothelial growth factor
(VEGF) aptamer
PEGylated erythropoietin
PEGylated recombinant
methionyl human
granulocyte colonystimulating factor
PEGylated synthetic peptide
analog of erythropoietin
PEGylated -asparaginase
(continued)
1 PEGylated Pharmaceutical Nanocarriers
9
Table 1.1
Brand name
PEGASYS Hoffmann-La
Pegintron Schering-Plough/
Pegloticase Savient Gout PEGylated uricase
Somavert Pzer Acromegaly PEGylated human growth
(continued)
Company Indication
Roche
Enzon
Comment
Hepatitis B and hepatitis CPEGylated interferon alpha
Hepatitis B and hepatitis CPEGylated interferon alpha
hormone mutein antagonist
1.2 PEGylation Determination
The method for quantitatively determining the degree of PEGylation of protein
bioconjugates utilizing 1H NMR spectroscopy and technical safety precautions is
presented in the chapter “Mechanisms of Activity Loss for a Multi-PEGylated
Protein by Experiment and Simulation” by Zaghmi etal. As an example of a
bioconjugate system, glutamate dehydrogenase (GDH), modied with several
copies of mPEG (0.5–20kDa), is employed. This quantitative approach can be
applied to additional proteins and is adaptable enough to function with other
polymers. An essential element for dening a bioconjugate is the quantity of
methoxy poly (ethylene glycol) (mPEG) chains attached to a protein (Zaghmi
etal. 2019).
1.2.1 Confirmation ofPEG Chain
PEG can be used in various lengths and densities to create PEG chains with mushroom or brush conformations. PEG shape affects protein corona patterns and the
relative abundance of different proteins in the corona. Clusterin is more likely to
bind to PEG chains with a brush shape, and serum albumin is deposited in the
corona at a lower rate. With restricted phagocytic uptake, the PEG brush shape in
the low protein absorbance regime and a surface enriched in clusterin results in the
stealth behavior of nanocarriers. The molecular structure of the grafted PEG chains
was determined by observing the 1H NMR relaxation time of the chains, which
offers details on the dynamics of macromolecular chains close to a solid surface.
Low grafting densities severely limit local segment mobility because polymer
chains spread out in a at manner over the surface. Polymer chains resist one another
and assume the shape of a longer “brush” when the grafting ratio rises. The correlation time of local segmental motions is crucial for understanding grafted polymer
chains’ dynamics. The spin-lattice relaxation time T1, which decreases as the
mobility of the polymer chains increases, is used to estimate this parameter (Li
etal. 2021).
10
P. Pingale et al.
1.2.1.1 Impact ofMolecular Weight ofPEG onMolecular
Confirmation Changes
The molecular weight of PEG impacts PEGylation of nanoparticles (Zhang etal.
2017a, b). Lu etal. reported that the diffusion rate of free heparin sulfate-PEG in
water decayed exponentially with an increase of molecular weight. It causes
enhancement in PEG density on the surface of nanoparticles as its molecular weight
decreases (Lu etal. 2019). Rabanel, Chan, and Teramura also noticed that a same
phenomenon occurred by the excluded volume impacts (Teramura et al. 2016;
Rabanel etal. 2019; Chan etal. 2020).
1.2.1.2 Impact ofSolvent onConformation Changes
The impact of solvent on the PEG conrmation is very substantial. Selli etal. evaluated the PEG chain’s conrmation on the surface of tin oxide nanoparticles using
various solvents, such as dichloromethane and water, based on atomistic molecular
dynamics simulations. In the presence of water, changes from a mushroom conformation to a brush conrmation begin only at a high density (2.25 chains per nm2). It
changes to brush conformation in dichloromethane because of more O
–Ti bonds
PEG
among the PEG (terminal group) and Ti atoms (2.25 chains per nm2) (Selli
etal. 2019).
1.2.2 Quantitative Determination ofSurface PEG Density
For more than 50years ago, experimental methods for measuring charge densities
on dielectric surfaces have been investigated. Surface charge densities (SCDs) were
initially determined through the examination of electrets. SCDs are now a hot topic
of study in elds like semiconductors, liquid crystals, and hybrid materials.
Quantitative information from the SCD can offer material-specic characteristics,
including details on lattice disruptions, an estimation of the degree of alignment, or
further information on interactions in compositions at the microscale. SCD measurements additionally provide the quantitative analysis of screening mechanisms.
Electrical characterization methods that do not involve touch are typically used to
measure the SCD.One can use the surface photovoltage effect to ascertain the SCD
when dealing with semiconductors. This method cannot be used with all materials
since it depends on producing electron–hole pairs by light. The vibrating probe
approach, invented in the 1960s and eventually evolved into a scanning technique,
provides a more versatile way to quantify SCD (Pannuzzo etal. 2020).
1.2.2.1 Thermal Gravimetric Analysis (TGA)
A sample is heated and continuously weighed in thermogravimetric analysis (TGA)
using an inert gas atmosphere. The most often used types are as follows:
1. Dynamic TGA: The temperature rises over time as the mass is measured. This
makes it possible to simultaneously determine how much gas is evacuated and
what temperature it occurs.
1 PEGylated Pharmaceutical Nanocarriers
11
2. Static TGA: The temperature is constant during the mass measurement. This can
be used to investigate a material’s resistance to a particular temperature or discover more about a decomposition that occurs at a particular temperature.
3. Semi-static TGA: The sample is repeatedly heated to various temperatures and
kept there for a long time until the mass stabilizes. This is ideal for looking at
substances that decompose differently at various temperatures and better characterizing how they decompose (De Blasio 2019).
They used to evaluate the thermal decomposition of PEG at temperatures ranging
from room temperature to 600°C in an N2 environment at a heating rate of 10°C/
min to distinguish between photo-dissociation of PEG and thermal dissociation.
PEG began to decompose at about 340°C and completed around 415 thermally. The
backbone chain’s -C-O and -C-C- bonds are considered, where PEG thermally
breaks down. Thermal dissociation only happens in a small temperature range
because PEG has a basic linear-chain-bond structure of 66% -C-O- and 33% -C-Cin the backbone chain with identical bond energies in the 82–83kcal/mol range. By
employing UV/O GPC, the substrate temperature was limited to 200°C, at which
thermal dissociation of PEG did not signicantly occur (Burkeyev etal. 2022).
1.2.2.2 Nuclear Magnetic Resonance (NMR)
When specic atomic nuclei are exposed to a strong enough xed magnetic eld,
they selectively absorb very high-frequency radio waves. This is known as
NMR.The initial observations of these occurrences were made independently in
1946 by the physicists Edward M.Purcell and Felix Bloch (Rinck 2019).
Because the signals from the repeating units overlap to produce prominent peaks,
polymer spectra frequently include carbon satellite peaks. A doublet evenly spaced
and cantered on either side of the principal peak makes up the signal for 1.1% of 1H
nuclei near a 13C.This splitting results in two smaller peaks for a sp3-hybridized C,
separated by 115–140Hz and representing the gyromagnetic ratio of 13C.The integration of each secondary peak is 0.55% of the primary peak. When present, this
splitting is typically overlooked because it occurs within the baseline for the majority of tiny molecules. For 2000 and 5000g/mol PEG, the ratio of the functionalized
terminal group to the repeating polymer unit is generally 2 to 0.9%; the 1H-13C
coupling can, nevertheless, become important when analyzing the functionalization
of polymers like PEG with a single functionalized terminal group. The integration
of a CH2 signal from the terminal (functionalized) group (e=3.55ppm) is therefore
close to that of the sidebands because of the 1H-13C link of the repeating CH2CH2- O unit (=3.46ppm) and the 5000g/mol PEG (Pasek-Allen etal. 2023).
1.2.2.3 Detection ofCoordination Complex
Neutral molecules or anions, often known as ligands, form coordinate covalent
bonds with a main metal atom (or ion) in a Lewis acid-base process. The nal product is a coordination complex. Coordination is the term used to describe the dipolar
“coordinate covalent bonds” between the ligands and the central atom. Initially, a
complex was believed to consist of reversible chemical bonds joining molecules,
12
atoms, or ions. In terms of coordination chemistry, the signicance has altered.
Relatively strong bonds join many metal complexes, creating specic metal complexes irrevocably (Li and Zuo 2020).
To make conjugates of monomethoxy-poly (ethylene glycol) and cisplatin
(MPEG-DA/CDDP), a poly (ethylene glycol) (PEG) derivative with a terminal
dicarboxylic acid group was coupled with cisplatin (CDDP) through chelate-type
coordination bonds. These conjugates have excellent anti-cancer efcacy, high
water solubility, and low adverse effects. The cytotoxic activity of the MPEG-DA/
CDDP compound was somewhat less than that of free CDDP. The MPEG-DA/
CDDP conjugation maintained a higher level of cytotoxicity even while treatment
in medium with serum lowered the cytotoxic property of free CDDP and the control
conjugate (Zhang etal. 2022).
P. Pingale et al.
1.2.2.4 X-Ray Photoelectron Spectroscopy
X-ray photoelectron spectroscopy (XPS), a quantitative technique for analyzing a
material’s surface’s chemical composition, also determines the constituent elements’ binding states. The normal XPS probe depth is 10nm. The material must
rst be evacuated because XPS needs a high vacuum before analysis begins. Photons
of specic energy are absorbed by electrons in a sample and released once the photon has left the material. XPS stands out for its popularity, adaptability, and utility
compared to many other techniques. Several applications will be used to demonstrate the adaptability and effectiveness of XPS.This reasonably practical technology might also be more exciting by looking at spectroscopic imaging and prospects
(Gengenbach etal. 2021).
The PEG lubricant’s spectra contained the high-intensity peaks C 1s at 285.09eV
and O 1s at 531.7eV.This demonstrated that most PEG lubricants comprised the C
and O components. Using XPS peak software, additional analysis of the two peaks
showed that the element C was present primarily as C-C, C-O, C-H, and C-N.Both
PEG monomers had signicant amounts of C-C, C-O, and C-H, although C-N predominated. The most prevalent form of the element O was C-OH.These outcomes
thus veried the inclusion of both PEGs in the manufactured lubricant. At 23.3°C
and 26.1°C, PEG showed two comparatively high, narrow, and strong diffraction
peaks, demonstrating a higher level of crystallinity. It can be seen that the composite
sample, which also included two reasonably high and narrow diffraction peaks at
23.3°C and 26.3°C, increased the strength of the peak at 23.3°C (Gao etal. 2022).
1.3 PEGylation ofNanocarriers
1.3.1 Nanoparticulate System
Nanoparticulate systems may be essential in imaging, surgery, and medication
delivery. Since nanoparticulate systems are more signicant than most “small molecule” type drugs but smaller than cells, they may have a longer retention time
(Dang and Guan 2020).
1 PEGylated Pharmaceutical Nanocarriers
13
1.3.1.1 Solid Lipid Nanoparticles
Solid lipid nanoparticles (SLNs) provide benets by minimizing some of the individual drawbacks of emulsions, polymeric nanoparticles, and liposomes. Typically,
they have a solid hydrophobic matrix core covered in phospholipids. Therefore, it is
envisaged that solid lipid nanoparticles will more effectively trap hydrophobic medicines in their core compared to traditional liposomes (Borges etal. 2020).
1.3.1.2 Nanostructured Lipid Carriers (NLCs)
When solid and liquid lipids are combined to create NLCs, the resulting structures
are less organized, allowing for a rmer inclusion of the drug molecules inside the
matrix over the course of the shelf life. The structural parity of two lipids in NLCs,
which has been consistently reported, causes defects in their structure and increases
space for drug accommodation during solidication, and is the cause of the improved
entrapment efciency in NLCs. Additionally, the more excellent solubility of medicines in liquid lipids compared to solid lipids is the cause of the increased entrapment efciency. NLCs have a higher payload capacity and lengthy shelf storage
stability than traditional lipid-based systems. Additionally, NLCs can include both
hydrophilic and lipophilic medications. They may also deliver medications to the
site of action and offer a prolonged release of the substances (Elmowafy and
Al-Sanea 2021). Numerous studies have demonstrated how these nanoplatforms
improve oral medication bioavailability by encouraging intestinal absorption. Due
to its ability to be sustained for extended periods and modulated by therapeutic
efcacy, this system has also given hope for treating chronic disorders.
Solid lipid nanoparticles (SLNs) were used to create the improved generation of
lipid nanoparticles known as NLCs. They minimize several SLN-related issues,
such as drug leakage during storage and a nite amount of drug that can be loaded
into them, while retaining many of the benets of SLNs, including regulated drug
release, biocompatibility, and the potential for large-scale industrial production.
According to reports, PEGylated nanoparticles have an increased half-life in circulation and are less likely to be absorbed by the RES (Garg etal. 2022). Additionally,
PEG can lengthen the time cancer cells are exposed to nanoparticles carrying an
anti-tumor medicine and can improve the enhanced permeability and retention. In
the current study, PEGylated NLCs (PEG-NLCs) were developed as carriers to stabilize the lactone form of HCPT, extending its duration in circulation and boosting
its anti-tumor efcacy against lung cancer. In this study, researchers discovered a
brand-new PEGNLC lung-targeting effect following i.v. injection in mice (Dhiman
etal. 2021).
1.3.1.3 Polymeric Nanoparticles
Polymeric nanoparticles have been used to treat various illnesses, including cancer,
diabetes, malaria, and tuberculosis. In comparison to other carriers, they offer several benets. The method of synthesis and choice of ingredients for the polymeric
nanoparticles depend on some factors, including the desired physicochemical qualities, the makeup of the medicine, and the expected course of therapy (Zielińska
etal. 2020).
14
P. Pingale et al.
1.3.2 Metal Nanoparticles
The use of metallic nanoparticles in several biomedical applications like bioimaging,
biosensors, target/sustained drug delivery, hyperthermia, and photoablation treatment, has gained popularity in recent years. Additionally, these nanoparticles have
been altered and functionalized with particular functional groups that enable them to
bind to medicines, antibodies, and other ligands, making these systems more attractive for use in biomedical applications (Jamkhande etal. 2019; Saravanan etal. 2021).
1.3.2.1 Silver Nanoparticles
Silver nanoparticles are extremely small silver atoms with sizes between 1 and
100nm. Ionic silver has a lengthy history and was rst employed in yellow-stain
glass, like gold nanoparticles. Work is currently being done to include silver
nanoparticles in various medical products, such as surgical masks, bone cement,
and other items. Additionally, it has been demonstrated that ionic silver can cure
wounds when used in the proper dosages (Yaqoob etal. 2020; Yin et al. 2020).
Silver nanoparticles have taken over from silver sulfadiazine as the preferred method
for treating wounds. On the surfaces of home appliances, Samsung has also developed and sold a product called Silver Nano that contains silver nanoparticles.
Additionally, these nanomaterials have drawn much interest in biological imaging employing SERS because of their appealing physiochemical features. Individual
silver nanoparticles are excellent candidates for molecular tagging due to their surface plasmon resonance (Abdelfattah etal. 2022). As a result, numerous targeted
silver oxide nanoprobes are being created right now. They are commonly produced
by reducing a silver salt in the presence of a colloidal stabilizer, such as sodium
borohydride. The most widely used colloidal stabilizers are polyvinyl alcohol, poly
(vinylpyrrolidone), bovine serum albumin (BSA), citrate, and cellulose. (Park etal.
2020). One of the more recent novel methods is ion implantation, which produces
silver nanoparticles using starch as a stabilizer and -glucose as a reducing sugar
(Abdel-Hameed etal. 2022). It is vital to remember that not all nanoparticles produced are made equally. It has been demonstrated that its effectiveness is inuenced
by its size and form. Elechiguerra etal. showed that silver nanoparticles interact
with HIV-1in a size-dependent manner, with particles in the 1–10nm range adhering to the virus (Elechiguerra etal. 2005).
1.3.2.2 Gold Nanoparticles
A suspension (or colloid) of gold nanoparticles is called colloidal gold, also called
gold nanoparticles. These colloidal solutions have a long history, from the Roman
era when they were employed to decorate glass with stains. These gold nanoparticles’ intriguing optical characteristics result from their particular interaction with
light. In the presence of the light’s pulsating electromagnetic eld, the free electrons
of the metal nanoparticles move in relation to the metal lattice (Zhang etal. 2021).
This mechanism, known as localized surface plasmon resonance (LSPR), is resonant at a specic light frequency. Following absorption, the surface plasmon degenerates either nonradiatively by turning the light absorbed into heat or radiatively,
leading to light dispersion (Sadalage etal. 2021). By precisely delivering AuNPs to
1 PEGylated Pharmaceutical Nanocarriers
15
the nucleus of cancer cells, El Sayed etal. used gold nanoparticles for cancer imaging. To specically deliver the AuNPs to the cancer cell nucleus, they coupled an
arginine-glycine-aspartic acid peptide (RGD) and a nuclear localization signal peptide (NLS) to a 30-nm AuNPs via PEG (Kang etal. 2010).
1.3.2.3 Titanium Dioxide Nanoparticles
There are two crystalline forms of titanium dioxide: rutile and anatase, the latter
chemically more active. Titanium dioxide ne particles (TiO2 FPs) are another name
for the rutile form of TiO2 nanoparticles. Compared to the rutile phase, the anatase
phase is signicantly more hazardous to healthy cells due to the increased crystalline structure of the anatase form, which increases the formation of reactive oxygen
species (Selli etal. 2019).
Additionally, the chemical modications made to nanoparticle surfaces vary in
how active TiO2 NPs are. In human SMMC-7721 hepatocarcinoma cells, for
instance, one-dimensional TiO2 Ws amplied the lethal effects of DNR by raising
its dosage. Similarly, combining TMZ with TiO2 nanostructures may enhance its
anti-tumor activity in treating brain gliomas (Shah etal. 2019; Siani etal. 2022).
Additionally, the release of valproic acid in several disorders was caused by its
gradual but persistent encapsulation in TiO2 matrices. Compared to their medications, GA and DNR from GA-TiO2 and DNR-TiO2 nanocomposites showed greater
potential anti-tumor efcacy in human leukemia K562 cells (Cin 2021).
1.3.2.4 Copper Nanoparticles
Copper nanoparticles (CuNPs) have become a more popular due to their accessibility, affordability, and potent anti-bacterial effects. CuNPs’ primary benet over gold
and silver nanoparticles is that they are less expensive and more readily available,
leading to sample synthesis and various uses for CuNPs. Copper nanoclusters
(Tf-CuNCs) with increased luminescence were formed due to experimental investigations on creating targeted medication delivery and bioimaging molecules (Okyere
etal. 2022). After being tested invivo on mice bearing Dalton’s lymphoma ascites
and the transferrin receptor (TfR), the newly created nanomaterials showed
improved tumor growth suppression and increased animal survival.
Curcumin-capped CuNPs have been identied by Kamble etal. as potential
inhibitors of human breast cancer cells and angiogenesis when compared to natural
curcumin (Kamble etal. 2016). Mupirocin-linked copper nanoparticles were created by Vikram etal. to overcome Staphylococcus aureus’s antibiotic resistance,
which causes cutaneous skin infections. CuNPs exhibit 96.5% drug release in an
invitro release study and have signicant antibacterial action against Staphylococcus
aureus (Verma and Kaushik 2020).
1.3.3 Vesicular Systems
Vesicular drug delivery systems have certain benets, including extending the duration of the medication’s presence in systemic circulation and possibly reducing toxicity if selective uptake is possible due to the drug being delivered directly to the
16
P. Pingale et al.
infection site. It enhances bioavailability, particularly for medicines that are difcult
to dissolve (Carter etal. 2019).
1.3.3.1 Liposomes
The Greek terms “lipo” and “soma,” which mean “fat” and “body,” respectively, are
the source of the phrase “liposome.” A hydrophilic “head” and a hydrophobic “tail”
(hydrocarbon chain) make up each phospholipid molecule. The self-association of
phospholipid layers during the spontaneous synthesis of liposomes takes place
(Mohamed etal. 2019). The liposome’s hydrophilic center is located between two
hydrophobic layers. With the help of this unique characteristic, we can insert hydrophilic or hydrophobic medicines between the two phospholipid layers (Singh
etal. 2020).
Due to their specic individuality, liposomes, vesicular nanocarriers, are widely
used as a successful delivery mechanism for brain targeting. A lipid bilayer surrounds an aqueous core in liposomes, simulating the structure of a cell membrane.
This distinction facilitates the fusing of liposomes with cell membranes and subsequent cell uptake. Because liposomes are amphipathic, they can be used to encapsulate hydrophilic and hydrophobic medications. Conventional liposomes have
drawbacks such as quick blood clearance and slow RES absorption because of the
accumulating plasma proteins (Ghaferi etal. 2020). Liposomes are quickly cleared
from the bloodstream and accumulate in the liver and spleen due to RES absorption.
Biocompatible PEG polymers have been used to stabilize conventional liposomes
sterically. In addition to passive accumulation in solid tumors, typical liposomes are
PEGylated to signicantly extend their half-life in circulation (Roces etal. 2020). It
was also attempted to directly couple ligands to the surface of the liposome using
PEGylated liposomes. However, the PEG chains showed a potent shielding effect
that prevented the attached ligand from interacting with its receptor. Targeting
ligands are linked to the ends of PEG chains to improve the vector’s exibility and
accessibility to the brain, where PEG is primarily used as a spacer (McSweeney
etal. 2019).
Transferrin (Tf)-anchored PEGylated liposomes loaded with horseradish peroxidase (HRP) and tested for their ability to target BCEC’s Tf receptor invitro. The
binding results of Tf-anchored liposomes were four times greater than those of conventional liposomes. Additionally, PEGylated liposomes were used to reduce RES
absorption and lengthen the time that polyethyleneimine/DNA (PEI/DNA) polyplexes remained in the body (Ko etal. 2009).
1.3.3.2 Niosomes
Due to the strict conditions needed to handle liposomes in cryogenic environments, the nonionic surfactant is now used in vesicular drug delivery systems
instead of phospholipids (Haroun etal. 2022). Niosomes can be altered or modied by adding additional excipients to the membrane, such as cholesterol, and
they can have one or more lipid bilayers surrounding an aqueous core (Haroun
etal. 2022). Niosomes have an internal structure that primarily combines hydrophobic and hydrophilic molecules, allowing them to accommodate medicinal