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8 PEGylated Nanocarriers forGene Therapy
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Several studies have demonstrated the emerging potential of PEGylated nanocarriers for gene therapy in brain cancer. For example, one study used PEGylated liposomes to deliver a gene that sensitizes brain tumor cells to chemotherapy, resulting
in signicant reduction in tumor growth in a mouse model of brain cancer. Another
study used PEGylated nanoparticles to deliver a gene that inhibits tumor growth and
increases the sensitivity of brain tumor cells to radiation therapy. In addition to sensitizing tumor cells to traditional treatments, gene therapy using nanocarriers can
also be used to deliver genes that enhance the immune response against brain tumor
cells. For example, a study using PEGylated nanoparticles to deliver a gene that
enhances the immune response in a mouse model of brain cancer which results in a
signicant reduction in tumor growth (Bruun etal. 2015).
Overall, the use of PEGylated nanocarriers for gene therapy in brain cancer
shows great promise as a targeted and potential treatment option. However, more
research is needed to optimize the design and delivery of these nanocarriers and
evaluate their safety and efcacy in clinical trials. Additionally, further studies are
needed to determine the most effective therapeutic genes to deliver via PEGylated
nanocarriers for the treatment of brain cancer (Wang etal. 2015b) (Table8.2).
8.4.2 Autoimmune Diseases
Autoimmune diseases refer to a group of disorders in which the immune system
mistakenly attacks the body’s own healthy tissues and organs, leading to inammation and damage. These diseases can affect various parts of the body, including
Table 8.2 Clinical status of PEGylated nanocarriers for cancer therapy
Types of
nanocarriers
PEGylated
liposomes
PEGylated
polymeric
micelles
PEGylated
polymeric
nanoparticles
PEGylated
polymeric
micelles
PEGylated
lipid
nanoparticles
Drug
loaded Indication Status
DOX Alleviated systemic toxicity
with increase in plasma
circulation half-life and
tumor accumulation
Dox Accumulation of drug in
solid tumor
Cisplatin Reduction in tumor growth Preclinical
PTX Alleviated systemic toxicity,
prolonged plasma circulation
half-life, increased tumor
accumulation and improving
in anticancer efcacy
Docetaxel Prolonged plasma half-life of
drugs along with substantial
accumulation at the tumor
site
Approved Hofheinz etal.
Phase 1
clinical
trails
trail
Approved in
South Korea
Preclinical
trails
References
(2005)
Matsumura etal.
(2004)
Mattheolabakis
etal. (2009)
Werner etal.
(2013)
Khalid etal.
(2006)
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joints, skin, muscles, blood vessels, and internal organs. Some examples of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, lupus, type 1 diabetes, inammatory bowel disease, psoriasis, and autoimmune thyroid disease. These
conditions may have a signicant impact on a person’s quality of life and may
require ongoing medical care and management. The exact causes of autoimmune
diseases are not fully understood, but it is assumed that a combination of genetic,
environmental, and lifestyle factors may play a role. Treatment options may include
medications to overcome inammation and suppress the immune system, as well as
lifestyle changes such as stress reduction and dietary modications. It is necessary
for individuals with autoimmune diseases to work closely with their healthcare providers to develop an appropriate management plan (Wang et al. 2015c; Wójcik
etal. 2021).
The treatment of autoimmune diseases probably involves medications to reduce
inammation and to suppress the immune system. The type of medication used will
depend on the specic autoimmune disease being treated, as well as the severity and
location of the symptoms. Some common medications used to treat autoimmune
diseases include: Nonsteroidal anti-inammatory drugs (NSAIDs), corticosteroids,
Disease-modifying antirheumatic drugs (DMARDs) (Beheshti et al. 2022; Afzal
etal. 2017).
While these medications can be effective in managing symptoms and slowing
disease progression, they may also have signicant limitations and potential side
effects. For example, long-term consumption of corticosteroids can increase the risk
of infections, osteoporosis, and other complications. Biologic drugs can be expensive and may increase the risk of infections and other side effects. Additionally,
while medications can help manage symptoms, they may not cure the underlying
autoimmune disease. Lifestyle modications such as stress reduction, exercise, and
a healthy diet may also play a role in managing autoimmune diseases and improving
overall health. It is benecial for individuals with autoimmune diseases to work
closely with their healthcare providers to develop an appropriate management plan
that considers the benets and limitations of various treatment options (Lim etal.
2019; An etal. 2020).
Gene therapy is a promising area of research for the management of autoimmune
diseases. The goal of gene therapy is to alter the genetic material of a patient’s cells
to correct the underlying cause of a disease. In the case of autoimmune diseases,
gene therapy could be used to modify the patient’s immune cells to reduce the overactive immune response that causes the disease. One approach involves using gene
editing approaches such as CRISPR to edit the genes responsible for the immune
response. Another approach is to modify the patient’s T cells or other immune cells
to target and destroy the cells that are attacking the body’s own tissues (Leung etal.
2010; Shu etal. 2015).
While the efciency of gene therapy for treating autoimmune diseases is exciting, there are still signicant challenges and limitations that must be overcome
before it can become a widely available treatment option. Some of these challenges
include safety concerns, delivery of therapeutics, and specicity. Despite these challenges, gene therapy holds signicant potential as a treatment strategy for
8 PEGylated Nanocarriers forGene Therapy
259
autoimmune diseases. Continued research and development in this eld could lead
to new and innovative therapies that offer more effective and targeted treatment
options for individuals living with autoimmune diseases. PEGylated nanocarriers
are a promising approach for delivering gene therapy to specic immune cells in
autoimmune diseases. These nanocarriers are made up of biocompatible materials,
such as lipids or polymers, and could be modied with PEG to increase their circulation time and reduce clearance by the immune system (Xue etal. 2015; Delogu
etal. 2009).
In the context of autoimmune diseases, PEGylated nanocarriers could be applicable to deliver therapeutic genes to modify the patient’s immune cells and reduce
the overactive immune response that causes the disease. The PEG coating on the
nanocarrier could help protect the therapeutic genes from degradation and immune
clearance, while also increasing their specicity for certain immune cells. Pegylated
nanocarriers for gene therapy has been studied in animal models of autoimmune
diseases and showed promising results in reducing disease severity and improving
outcomes. For example, in a mouse model of rheumatoid arthritis, PEGylated nanocarriers were shown to deliver therapeutic genes specically to the inamed joint
tissues, leading to a reduction in inammation and joint damage. One advantage of
using PEGylated nanocarriers for gene therapy in autoimmune diseases is their ability to target specic immune cells, which can help reduce the risk of systemic
immunosuppression and other side effects associated with non-targeted therapies.
Additionally, PEGylated nanocarriers may be able to overcome some of the delivery
challenges associated with traditional gene therapy approaches (Ren etal. 2019).
8.4.3 Inflammatory Disorders
Chronic, persistent inammation plays a wide role in the clinical development of
advanced atherosclerotic lesions. After being administered to mice, Col IV-targeted
PLGA nanoparticles encasing Ac2-26 (capable of simulating the pro-resolving
effects of annexin A1) were investigated for therapeutic effectiveness in chronic and
advanced atherosclerosis. Col IV-Ac2-26 PLGA NPs signicantly reduced plaque
necrosis suppressed oxidative stress, and advanced plaque properties, indicating
that targeted delivery of a resolution-mediating peptide activated receptors over
myeloid cells to stabilize advanced atherosclerotic lesions (Fredman etal. 2015).
Super paramagnetic iron oxide nanoparticles included in PLGA nanoparticles can
also be employed for the treatment of joint inammation, suggesting a possible way
to prevent the generation of inammatory responses in joint illnesses (Gu etal.
2013). Reduced interchange with the mononuclear phagocyte system has been seen
in PEGylated PLGA nanoparticles, which results in reduced development of immunological responses (Ikoba etal. 2015).
Crohn’s disease and ulcerative colitis are two examples of the chronic relapsing
GI disorders that fall under the umbrella label of “inammatory bowel disease”
(IBD). Mucosal inammatory cycles that come and go are a dening aspect of
Ulcerative colitis (UC) and crohn’s disease (CD). Both disorders frequently impact
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the whole colon, necessitating colon-specic medication administration to treat
inammatory bowel disease (IBD) (Hua etal. 2015). To test its application in an
experimental model of ulcerative colitis, chitosan (CS)-modied PLGA nanospheres (NS) with a nuclear factor kappa B (NF-kB) decoy oligonucleotide (ODN)
oral delivery system were created. Dextran sulphate sodium-induced diarrhea was
signicantly improved by decoy ODN-loaded CS-PLGA NS, and bloody feces and
myeloperoxidase activity were also signicantly increased. These results suggest
that CS-PLGA NS might be a useful method for colon-specic oral decoy ODN
delivery in UC (Tahara etal. 2011).
Targeted drug delivery devices of nano range with potential to particularly aggregate in inamed mucosal tissues might lessen adverse medication responses in association with oral administration of anti-inammatory as well as immunosuppressive
pharmaceuticals for the treatment of IBD.Different PLGA micro- and nanoparticles
with PEG-surface functionalization demonstrated enhanced translocation and deposition in inamed mucosa and recognized as an avant-garde method of treating IBD
(Lautenschläger etal. 2013).
8.4.4 Cardiovascular Diseases
Despite notable clinical advancements, cardiovascular diseases (CVDs), which
include a variety of heart and blood vessel illnesses as well as stroke, continue to be
the emerging cause of death in the United States. As per estimates from the World
Health Organization (WHO), about 25 million deaths worldwide will be attributable
to CVDs by 2030 (Lloyd-Jones etal. 2010; Tucka etal. 2012). For use in CVDs,
numerous nanostructures-based drug delivery systems, particularly those made of
biodegradable PLGA, are being developed. These systems feature a variety of sizes,
shapes, as well as surface functionalization, as well as a huge range of electrostatic
charges and bio-molecular conjugations (Cristallini et al. 2016; Pascual-Gil
etal. 2017).
Controlled imaging and medication delivery in order to treat atherosclerosis,
myocardial infarction, restenosis, and other cardiovascular disorders have been one
of the key applications of nanotechnology in the cardiovascular investigation. An
unfavorable consequence of endovascular procedures is restenosis, which is the narrowing of a blood vessel and results in constrained blood ow. Numerous medications, such as cytotoxins, inhibitors of the growth of smooth muscle cells (such as
paclitaxel, etoposides, cytarabine, and doxorubicin), immunomodulators (such as
steroids and bisphosphonates), inhibitors of the receptor for platelet-derived growth
factors (PDGF), such as tyrphostin, antibiotics (such as fumagillin), and gene therapy, are used to prevent this restenosis. These biomolecules and genetic components
are enclosed in polymeric nanoparticles to create regulated release patterns while
protecting them from unintended enzymatic breakdown. By creating PLGA-based
nanoparticles that are coated with AGL 2043 and AG1295, two specic PDGF
receptor protein tyrosine kinase blockers, restenosis is prevented in rats with
balloon- injured carotid arteries (Godin etal. 2010).
8 PEGylated Nanocarriers forGene Therapy
261
Life-threatening disorders include peripheral artery thrombosis, ischemic stroke,
deep vein thrombosis, ischemic stroke, myocardial infarction, and pulmonary
embolism resulting from the development of a thrombus in the blood circulatory
system. For the therapy of these illnesses, numerous plasminogen activators have
been developed. Plasminogen activator-loaded PLGA and PEG copolymer microspheres showed that they can successfully retain medication and release it at the
target spot in concentrations of more than 4mg/mL.The enhanced thrombolysis is
demonstrated by pressure-driven permeation into the clot’s interior. However, brin
clot pores exhibit resistance to the admission of carriers 1m or larger into the clot
interior when there is no hydrodynamic pressure. Therefore, chitosan (CS) and
CS-GRGD coated, PLGA NPs loaded with PA were created, and their capacity for
thrombolysis was examined in a blood clot-occluded model. The shortest time range
for clot lysis was shown by PLGA/CS NPs, while the highest percentage of digested
clots was shown by PLGA/CS-GRGD NPs. By demonstrating persistent adhesion
and aggregation of the clot font and interior, these nanoparticles displayed enhanced
penetration (Vyas and Vaidya 2009).
Depletion of myocardiocytes and brosis result in myocardial ischemia (MI),
which causes cardiac dysfunction. Delivery of recombinant protein or DNA forms
of proangiogenic cytokines, such as growth factors includes vascular endothelial,
hepatocyte, or broblast growth factor 1 and 2 (VEGF), (HGF), and (FGF-1 and -2),
increases neovascularization of ischemic heart tissue and reduces dysfunction.
Moreover, issues regarding growth factor delivery have resulted in the administration of synthetic compounds that can increase the release of endogenous proangiogenic cytokines. By polymerizing ONO-1301 with PLGA, a slow-release version of
the prostacyclin agonist ONO-1301 (SR-ONO) were created. The results of the current investigation demonstrated that ONO1301 greatly accelerated with recovery of
perfusion in the rat’s hind leg and boosted endogenous HGF production. However,
epicardial injection of SR-ONO in case of swine chronic ischemia enhanced local
wall motion of ventricles, encouraged collateral development, and decreased left
ventricle hypertrophy. The tissue can progressively absorb PLGA without suffering
any harm. The oral administration of SR-ONO has not been related to any side
effects such as diarrhoea, hypotension, or tachycardia (Iwata etal. 2009).
To combat hypoxia and its aftereffects, angiogenic therapy with vascular endothelial growth factor (VEGF) is an effective approach. It has been demonstrated that
PLGA particles which are loaded with VEGF are an efcient method for delivering
cytokines to a rat myocardial ischemia model. This strategy might be investigated
further for various clinical investigations (Formiga etal. 2010). The compelling
evidence supporting the contribution of oxidative stress to MI supports the utilization of antioxidants. Because of its function in the mitochondrial electron transport
chain, Coenzyme Q10 (CoQ10) seems like a good choice to treat MI; however,
because of its poor biopharmaceutical qualities, there is a need to nd effective
delivery methods. CoQ10 was given to rats with MI after being encapsulated in
PLGA-based nanoparticles, which improved the draggability of CoQ10. Ejection
fraction measurements were made before and after 3 months of treatment to
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L. Mishra et al.
examine cardiac function. The ejection fraction signicantly improved after
3months, according to the results (Simón-Yarza etal. 2013).
Early reperfusion has been demonstrated to be a conventional method for reduction in myocardial infarction size in MI patients to achieve improved clinical outcomes. Myocardial ischemia-reperfusion (IR) injury is described as the paradoxical
death of cardiomyocytes caused by reperfusion of coronary arteries. Inammatory
mediators, in particular monocytes, are signicant pathogenesis-related factors,
making them prospective therapy targets for IR injury. Irbesartan, which is an
angiotensin receptor blocker (ARB), was incorporated into PLGA nanoparticles
and examined in a mouse model having IR injury. A single IV dosage of PLGA
nanoparticles demonstrated improved distribution inside the mouse heart’s myocardium and monocytes. Irbesartan nanoparticles have demonstrated efcacy in inhibiting monocyte recruitment in the IR heart and greatly reduced down the size of
infarct. These results support their use as a therapeutic treatment for myocardial IR
injury (Nakano etal. 2016).
Current developments in interventional cardiology using PCI and various revascularization techniques have improved the symptoms of CVDs. However, the atherosclerotic disease continues to be the emerging cause of death in the world. To
enhance patient prognosis, new treatments must be developed that can interfere with
underlying biological pathways responsible for disease pathogenesis. The development of several genetic models, such as that of atherosclerotic heart disease, has
given rise to the crucial concept of using gene therapy to create novel treatments for
CVDs. A hallmark of atherosclerosis development is inammation of the arterial
wall involving monocytes. As a result, monocyte chemoattractant protein-1 (MCP-1)
and its receptor chemokine receptor 2 (CCR2) are promising target sites for gene
therapy in the prevention of monocyte-regulated inammation in atherosclerosis.
7ND, a mutant MCP-1 lacking the N-terminal 7 amino acids, is capable of binding
with CCR2 and inhibiting MCP-1-mediated monocyte chemotaxis. A suitable gene
delivery system has been created using PLGA.In mice with hypercholesterolemia,
gene treatment with the 7ND plasmid encased in PLGA nanoparticles inhibited
atherosclerosis. Finally, gene therapy uses a cutting-edge NP-regulated gene delivery system that targets MCP-1/CCR2 signals which is an efcient therapeutic
method for the treatment of cardiovascular diseases (Matoba and Egashira 2011).
8.4.5 Ocular Diseases
Despite the fact that the eyes are generally accessible, multiple hurdles in effective
drug delivery prevent potential treatment of the various blindness disorders which
affect the eyes. The common frequent method of eye administration is topical drops,
but due to quick clearance as well as poor absorption, less than 5% of the administered dose reached in intraocular tissues (Järvinen etal. 1995). NPs have been investigated as a method of extending the residence time and penetration of medications
delivered to the ocular surface. Giannavola and colleagues investigated the use of
PEG which works as a mucoadhesive to increase contacts between acyclovir-loaded
8 PEGylated Nanocarriers forGene Therapy
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PLA NPs and the eye’s surface (Giannavola etal. 2003). Despite being mostly
described as a mucoinert surface coating thus far, PEG has a wide history of application in promoting mucoadhesion by interpenetration and/or hydrogen bonding
with the mucus (Wang etal. 2008).
Furthermore, one more recent research by Schopf and colleagues which suggested to applied topically to the surface of the rabbit eye, loteprednol etabonate
(LE) delivery in to the cornea as well as retina was increased by nanoparticles
coated with a dense, mucoinert PEG surface coating when compared to nanoparticles without having a mucoinert PEG surface coating. The fact that nanoparticles
(240nm) and not microparticles (>1m) beneted from the mucoinert surface coating suggests that the nanoparticles (LE-MPP) were able to enter the membranebound eye mucus layer, resulting in a prolonged residence time and efcient drug
delivery. Then, in a pigmented rabbit model of increased retinal vascular permeability, they showed that topical LE-MPP dramatically reduced vascular leakage
(Schopf etal. 2015).
Mun and colleagues sought to better understand the cornea’s ability to block
uorescently labelled nanoparticles (NPs). They delivered thiol-functionalized silica nanoparticles (thiol NPs) and silica particles incorporated with 750 or 5000Da
PEG to bovine eyes that were purchased from a butcher 1 day before use. The different NP solutions were exposed to the central cornea of the eyes while they were
housed in a beaker with a Franz cell donor chamber on top. They discovered that the
thiolated silica NPs (21–45nm) stuck onto the cornea’s surface even when the epithelium had been removed before exposure. Similar ndings were obtained for the
750Da PEG-functionalized silica particles (27–54nm). When the epithelium was
removed before the procedure, the silica NPs functionalized with 5000Da PEG
(43–69nm) penetrated the stroma but not the intact cornea. The stroma is more of
an aqueous layer with small resistance to transcorneal permeation, whereas the corneal epithelium acts as the primary barrier restricting drug absorption in the eye.
This is why they hypothesized that the difference in penetration between the corneal
epithelium and the stroma was caused by the different barrier characteristics of the
tissue layers (Mun etal. 2014).
Injections into an eye are frequently utilized to get over the several obstacles in
order to delivery in front of the eye, especially for medication administration to the
rear of the eye. Even though the vitreous gel still presents a considerable obstacle to
efcient retinal administration, intravitreal injections are frequently employed to
deliver inside the retina. Sanders and colleagues investigated how PEGylation
affected DNA NPs for retinal gene delivery. They reasoned that PEG coatings can
boost the mobility and vitreous penetration, would likely bring them closer to the
target cells for the transfection, but they would not like to compromise the DNA
NPs’ efcacy of transfection. By adding DNA to cationic liposomes made of
DOTAP and DOPE lipids, they created DNA NPs. The DSPE-PEG lipids in the
“pre-PEGylated” lipoplexes were afterwards coated with DNA.
In order to create the “post-PEGylated” lipoplexes, non-PEGylated lipoplexes
were rst created and then treated with ceramide-C8-PEG lipids. Within 30min of
the animal’s death, they retrieved the vitreous from its eyes and added the different
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lipoplexes. When the non-PEGylated lipoplexes were injected into the vitreous,
they discovered that they greatly aggregated. While the 17 mol% PEG prePEGylated lipoplexes looked stable and evenly dispersed following injection inside
the isolated vitreous, the addition of 4mol% PEG in pre-PEGylated lipoplexes did
give stability. Non-PEGylated and 4mol% pre-PEGylated lipoplexes were found to
be immobilized in the vitreous whereas the 17 mol% pre-PEGylated lipoplexes
were shown to be mobile by uorescence recovery after photobleaching (FRAP).
The pre-PEGylation (using DSPE-PEG) signicantly reduced the invitro transfection of retinal pigment epithelium (RPE) cells, which were later discovered. The
researchers went on to show that although the post-PEGylated lipoplexes retained
stability in the vitreous, they were internalized by RPE cells similar to that of nonPEGylated lipoplexes. Thus, they showed that it was able to create DNA lipoplexes
wrapped in PEG to increase vitreous stability while maintaining invitro RPE cell
transfection (Sanders etal. 2007).
8.4.6 Drug Delivery toCentral Nervous System (CNS)
The frequency of neurodegenerative illnesses has grown due to population ageing
and their widespread distribution. Alzheimer’s disease (AD), which affects more
than 35 million people globally, and by 2050, that number is projected to be double
(Gregori etal. 2015). Because the blood-brain barrier (BBB) majorly prevents drugs
from reaching the central nervous systems, present therapies are ineffective and new
drug delivery mechanisms must be developed. Particularly PLGA-based polymeric
nanoparticles have proven useful for this purpose (Fazil et al. 2012; Vilella
etal. 2015).
In order to demonstrate that loperamide-loaded PLGA nanoparticles may effectively cross the BBB, their surfaces were functionalized with the help of monoclonal antibody for active targeting towards the transferrin receptor (Fornaguera etal.
2015a). A further neurodegenerative condition is Parkinson’s disease. To obtain a
neuroprotective effect in parkinsonism brought on by reactive oxygen species
(ROS), poly (lactic-co-glycolic acid) (PLGA) nanoparticles were produced (Jo
etal. 2015). Lorazepam-loaded PLGA nanoparticles were successfully created utilizing the nanoprecipitation process. Drug release characteristics invitro were discovered to be almost identical to sheep nasal mucosa exvivo penetration studies.
Through an invitro cell viability assay, the safety of NPs was assessed using the
Vero cell line. Lzp-PLGA-NPs were radiolabeled with Technitium-99m in order to
create a nose-to-brain bio-distribution route in rats models using scintigraphy imaging (Sharma etal. 2014). Despite intensive investigation into cerebral vasospasm
therapy, the fate of different patients with subarachnoid hemorrhage (SAH) remained
disastrous. An important underlying mechanism for the development and maintenance of early brain damage (EBI) is inammation after SAH.Curcumin is enclosed
in PLGA for increasing its solubility-related concentration and provide a potent
anti-neuroinammatory reaction in the affected CNS.In a mouse model of SAH,
delivery of nanocurcumin decreased leukocyte chemotaxis and subsequent
8 PEGylated Nanocarriers forGene Therapy
265
inammation, indicating that the herb’s nanoparticles would be clinically effective
to reduce the apoptosis brought on by SAH (Chang etal. 2015).
Resveratrol is a polyphenolic molecule that is abundant in grapes, blueberries,
mulberries, cranberries, and peanut sprouts. It has anti-aging, cardioprotective, anticancer, and protective benets against PD features. Its encapsulation in PLGA
nanoparticles prevents it from being converted from its trans form into its inactive
cis form, increasing its bioavailability and prolonging the anti-Parkinson effects
shown in a rat model for up to 4days (Ganesan etal. 2015). One of the most major
neurodegenerative conditions that causes dementia is Alzheimer’s disease (AD).
The main characteristic of this illness, which causes the production of extracellular
aggregates, is the deposition of amyloid (A). Curcumin exhibits anti-amyloidogenic
activity in order to inhibit the formation of fresh A aggregates and dispersing the
ones that are already present. Because curcumin cannot effectively penetrate the
BBB, the brain absorbs less of it. Curcumin was therefore enclosed in PLGA NPs
to increase its BBB-crossing capacity. Hippocampal cell culture invitro investigations have not revealed any harm. Further evidence that curcumin loaded PLGA
NPs are viable carriers for effective AD treatment comes from the considerable
decrease in aggregation caused by these NPs (Barbara etal. 2017).
In various animal models of Alzheimer’s disease, siRNAs and miRNAs are frequently delivered via PLGA nanoparticles. In order to enhance the characteristics of
nanoparticles, various chemicals, proteins, and nucleic acids can be introduced into
the PLGA matrix. Emerging nanotechnology-based delivery technologies may be
employed for miRNA treatment in illnesses of the central nervous system (Shi
2015). One other study has shown that PLGA nanoparticles may be used to create
the most effective and secure Alzheimer’s disease vaccine. In present work, PLGA
nanoparticles were created to encapsulate an A-1-15 amino acid-containing peptide
for the subcut or intranasal immunization of Balb/c mice. Elicited Abs titers against
complete A have been seen in mice (Puras etal. 2011).
Demyelination progresses over time in the central nervous system disorder
known as multiple sclerosis (MS). Insulation, metabolic support for axons, and
assistance with electrical signal transmission are all functions of the myelin sheath.
Demyelination causes permanent neurodegeneration and loss of electrical conduction, which calls for an efcient therapeutic strategy. Leukemia inhibitory factor
(LIF), which is a cytokine that promotes self-immunological tolerance, is a promyelination factor. LIF is delivered using PLGA nanoparticles that have been surface
functionalized with antibodies against NG2 expressed on oligodendrocyte precursor cells (OPCs). This promotes the differentiation of OPC precursor cells inside the
mature oligodendrocytes that can repair myelin. Both degrees of myelin repair were
seen, and the increased number of myelinated axons and enhanced myelin thickness
per axon imply that this method may be used to treat multiple sclerosis (MS)
(Rittchen etal. 2015).
PLGA has been used to create GAL-loaded nanoparticles with improved encapsulation effectiveness, a regulated drug release prole, a non-toxic effect, and the
preservation of GAL’s pharmacological activity, lengthening the duration of its
therapeutic benets. These improved GAL-loaded nanoparticles are a potential
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medication delivery method for neurological disorders (Fornaguera etal. 2015b).
Additionally, nanopatterned scaffolds made of PLGA has been created to increase
the therapeutic potential of stem cells in treating illnesses such as brain damage and
neurodegenerative disorders. Neuronal stem cells (NSCs) are being stimulated to
extend their neurites and are being controlled in their development using biophysical signals provided by nanotopographical characteristics. Biodegradable PLGA
polymeric substrates with nanoscale topographic features were created with DOPA
(dihydroxyphenylalanine) coating for guided neurite outgrowth and improved differentiation of human neural stem cells (hNSC). With the addition of nerve growth
factor, hNSC differentiation was signicantly enhanced, demonstrating the joint
impact of biochemical as well as physical cues on stem cell differentiation (Yang
etal. 2015).
8.5 Conclusion
Due to their capacity to shield genetic material from deterioration and enhance its
reception into cells, PEGylated nanocarriers are a potential technique for gene
transfer. Future developments in this area can be anticipated as researchers attempt
to improve the functionality and efciency of PEGylated nanocarriers for gene therapy applications. How to combat the immunological response that can be brought
on by PEGylated nanoparticles is one of the major issues that researchers will need
to address. Finding ways to lessen this response will be a key area of attention as it
may restrict their efcacy and lead to negative patient reactions. The use of
PEGylated nanocarriers for targeted gene therapy, in which particular genes are
delivered to particular cells or tissues in the body, will also be investigated in future
studies. This might be accomplished by altering the nanocarrier’s surface with targeting molecules that recognize and bind to particular cell types. As a tool for gene
therapy, PEGylated nanocarriers show great potential, and as scientists seek to solve
the remaining issues and rene the technology for clinical application, we may
anticipate seeing further advancements in this area. Before PEGylated nanocarriers
can be extensively used as a gene therapy tool, extensive safety and efcacy studies
must be carried out because, like any new technology, there are still numerous unresolved issues and possible dangers.
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