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216 Carbon-Based Nanocarriers for Drug Delivery
quantities in dendrimer-liposome hybrids because dendrimer synthesis increases drug
loading [119]. Drug loading effectiveness is impacted by the drug dendrimer-to-lipid
molar ratio in the liposome. Amolar ratio of 10:10:0.1 was found in two liposomes
containing hexadecylphosphocholine (HePC), egg yolk phosphatidylcholine (EPC),
and stearylamine (SA) (molar ratio). Efciency was 91% and 95%, respectively, when
Doxorubicin (Dox)-PAMAM dendrimer (3:1 and 6:1 molar ratio) was coupled with
both kinds of liposomes. At pH 7.4 (TES buffer) compared to pH 4.5 (acetate buffer),
drug encapsulation was greater, and Dox release from the liposome was very sluggish
(17% at pH 7.4 and 25 °C even after 24 h). Dox entrapment was enhanced at pH 7.4.
Due to the interaction between the drug and the dendrimer, Dox-dendrimer incorporation into liposomes was higher at 3:1 than 6:1 in both buffers. The study claimed cytotoxic experiments against lungs (DMS114, NCI-H460), colon (HT29, HCT116), breast
(MB435k, MCF7), prostate (DU145), and central nervous system (CNS) (SF268) cancer cell lines and discovered that MDA-MB435, DMS114, and NCI-H460 were the
most sensitive [120]. As drug carriers, dendrimer-liposome hybrids are commonly
utilized because of their enhanced permeability and retention (EPR) effect and better
drug encapsulation efciency. Due to their ability to overcome hurdles, it is vital to
research dendrimer-liposome hybrids as feasible nanocarriers in nanotherapeutics.
NPs range in size from 1 to 100 nm and can be amorphous or crystalline. NPs are
the most common nanocarrier for the delivery of medications due to their increased
surface area and quantum size effects. In 2002, PEG-grafted PAMAM-NH2 dendrimers were used to create gold and cadmium sulde nanoparticles (NPs). As a
template, star polymer can strengthen polydispersed NPs and improve miscibility
in organic solvents. Dendrimer-grafted NPs is depicted in Figure 8.2 [114]. On
magnetite-modied aminosilane NPs, PAMAM dendrimer was generated. Due to
the enormous size of BSA and the small surface area of NPs, BSA immobilization
increased linearly with dendrimer production. Immobilization outperformed amino
silane-modied NPs by 3.9–7.7 times [121].
Dendrimers are typically mononuclear micelles. In the aqueous phase, SiO2 NPs
are stabilized by dendrimers by preventing photocatalysis [122]. Unexpectedly, dendrimers also signicantly inuenced the size, shape, size distribution, and stability of silver NPs produced using co-mediators such as polyvinyl pyrrolidone (PVP)
and PAMAM G1.5 dendrimers. The diameter of spherical NPs was around 5 nm.
During at least two months at room temperature, these NPs did not aggregate. NP
size and distribution are similarly impacted by oligosaccharide (maltose)-modied
poly(propylene imine) glycodendrimers as templates. G4 (1–2 nm) (1–2 nm) Due
to their autoreductive property, maltose-modied dendrimers produced the smallest
NPs; unmodied dendrimers did not. Due to the interfacial absorption of larger NPs,
lower-generation dendrimers (G2-G3) were more stable. In well-dened cavities,
dendrimers can serve to stabilize smaller NPs [123]. Platinum (Pt) NPs stabilized by
carbosilane dendrimers via the Pt-C link and showed excellent dispersibility in situ
with a range of sizes [124].
Terminal functionality allows NPs to self-assemble into the G2-G5 thiolterminated PAMAM dendrimer. Bridging aggregation regulated NP-dendrimer
aggregation. Dendrimer production increased steric hindrance, shrinking the
cluster. Dendrimer production and NP diameter inuence interparticle spacing.
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FIGURE 8.2 Dendrimer-Grafted Nanohybrid. Reprinted with permission from Kesharwani
et al. (2018)] [114].
Higher-generation PAMAM stabilized silver (Ag)/AuNPs (G5). Dendrimer- entrapped
and dendrimer-stabilized NPs (DENPs and DSNPs) for computed tomography (CT)
imaging and other biological applications were promisingly cytocompatible [125].
Dendrimers dictate NP sizes and morphology. The polypropylene imine (PPI)
G3 dendrimer molar ratio affects the size of the AuNP nanocomposite. Dendrimer-AuNP interaction and particle growth at higher molar ratios yield smaller NPs
[126]. PAMAM- dendrimer-modied ternary magnetic iron oxide NPs/DNA/PEI
magnetoplexes improve NP transfection. Magnetofection swiftly accumulated magnetoplexes and absorbed them in a magnetic eld in COS-7 cells [127].
The dendrimer-NP hybrid has been used in a number of different elds, both
biological and nonbiological, such as electrochemistry, catalysis, and immunological sensors. Palladium (Pd)NP forms the 2.7 nm carbon-Pd stabilized Frechet type
G1 dendrimer (Pd-G1). It catalyzes double-bonded compounds. The complex is
reusable, responds fast, and produces a lot of products at room temperature. Halogens and endocyclic double bonds were unaffected [33]. PPI-dendrimers were used
218 Carbon-Based Nanocarriers for Drug Delivery
to make a chemoresistor, vapor-sensing nanocomposite lm, and layer-by-layer
(LbL) dendrimer self-assembly AuNPs (G1–5). Dendrimer synthesis solvated toluene and 1-propanol vapors, boosting chemical sensitivity. Water vapor was unaffected, and nanocomposites’ resistivity was dictated by dendrimer synthesis and
size, which controlled NP concentration [128]. The NP-dendrimer composite was a
stimuli- responsive sensor because chemical species from the vapor phase impacted
its conductance. In various solvents, AuNP lm included dendrimers PAMAM (G3)
and PPI (G4). Au-PPI was 27.8 nm thick and Au-PAMAM 36.6 nm. Although the
aliphatic chain was insufcient to form a strong interaction with nonpolar molecules
like toluene, a large number of polar amide and tertiary amine groups of PAMAM
and PPI of the lms served as receptors and formed H-bonds with proton donors like
water, suggesting that the NP-dendrimer lm could be used as a chemiresistive vapor
sensor [129]. Electrochemically, PAMAM (G4) dendrimer-encapsulated AuNP nanocomposites recognized α-synuclein. Parkinson’s, Alzheimer’s, and Huntington’s have
α-synuclein pathology. Dendrimer encapsulated in AuNP was covalently bonded to
the electrode, and horseradish-peroxidase-secondary-antibody (HRP-Ab2) coupled
to NPs increased signals (15.6 nm). Systems responded at 14.6 pg mL−1α-synuclein.
Due to the increased number of amino groups in the dendrimer and HRP-Ab2, dual
signal amplication occurred. Thus, the study recommended expanding the hybrid
to approaches for protein analysis [114].
Bimetallic NPs were synthesized from OH-terminated PAMAM G4 dendrimers
that partially hydrogenated 1,3-cyclooctadiene, indicating the dendrimer’s potential application as a nanoreactor in NP production [130]. An LbL lm was made
utilizing an electroactive nanostructure membrane (ENM) with alternating layers
of AuNP-dendrimer (amine-terminated, G4) and poly (vinylsulfonic acid). PVS/
PAMAM-AuNP electrodes reduced oxygen for three bilayers better than ITO
electrodes [131]. Adendrimer-NP cisplatin delivery method was reported wherein
Herceptin-conjugated PAMAM dendrimers and diglycolamic acid were utilized.
HER-2-positive and HER-2-negative ovarian cancer cell line tests showed that the
nanoconstruct lowered IC50 values for cisplatin. Targeted conjugate administration
boosted anticancer activity in SKOV-3 tumor xenografts [132]. EPR stabilized a multistage nanocarrier in systemic circulation and accumulated in the tumor by encapsulating PAMAM dendrimer (5 nm). Loading MTX enhanced tumor penetration and
effectiveness [133]. Dendrimers increased magnetic nanoparticle tumor cell capture,
water solubility, and antibody conjugation (MNPs). Nanosubstrate accelerates tumor
cell identication and collects 86 ± 5% [134].
Dendrimer-quantum-dot hybrid QDs are semiconducting, spherical, bright nanocrystals with a radius of 10–100. Size inuences their attributes. QDs are employed
for in-vivo applications, in-vitro bioimaging, uorescence, greater chemical stability,
readily changeable spectrum characteristics, narrow emission, broad UV excitation,
and superior photo-stability. Dendrimer-QD hybrids improved QD quantum yield,
water solubility, and toxicity [114].
PAMAM dendrimers encapsulate Cadmium Sulde (CdS) QDs in a nanocomposite with all the previously mentioned properties [135]. PAMAM G4 dendrimers
tagged with 525 ITKTM(PEG) QDs target the vimentin shRNA plasmid for imaging.
The EGF-conjugated dendrimer targeted NIH3T3 and HN12 cells via EGFR, which
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is overexpressed in the cell lines. EGFR on the cell membrane, nuclear membrane,
and cytoplasm allowed the conjugate system into endosomes. EGF’s positive charge
attracts receptors. Drugs or nucleic acids feed growth factors. The QD-PAMAM
G4-aptamer GBI-10 combination improves targeted administration, water solubility, and Apt-QD nanoprobe binding afnity against U251 glioblastoma cells. GBI10 recognizes tenacin-C, an extracellular protein on human U251 cells; nanoprobes
strongly bind to the cells [136]. RGD peptide enhances dendrimer-QD hybrid imaging and targeting. Melanoma, sprouting tumor vasculature, glioblastoma, breast,
prostate, and ovarian cancer overexpress integrin V3, which interacts with the RGD
peptide—conjugated nanoprobes image A375 melanoma cells and HUVECs in-vitro
and in-vivo. RGD-conjugated QDs were biocompatible and non-cytotoxic [137].
Dendrimer-CdTe QDs reduce Cd release and cytotoxicity. PAMAM G3.0
dendrimer-CdTe QD nanoconjugate may be transfected into PK15 cells for cell-imaging. CdTe-PAMAM cell survival was 75.28% after 48 hours and 25.23% after
12hours using CdSe QDs. Dendrimer-modied QDs have signicantly low cytotoxicity [114]. Graded band gap construction and QD LbL deposition enabled FRET
to detect DNA hydrolysis. QDs modied with PAMAM dendrimer improve cellular
uptake, cytosolic distribution, and intracellular uorescence in primary MSCs.
Nonbiological applications used diaminobutane-based CdS, ZnS, and CdS/ZnSQDS nanocomposites. pH, ionic strength, and Hg(II) nanosensors use nanocomposites [138]. Glass carbon electrodes can electrochemically monitor waterborne
bisphenol A [2,2-bis(4-hydroxyphenyl)propane] using CoTe QDs with PAMAM
dendrimer. The method has a lower oxidation potential, improved sensitivity, lower
detection limits, and shorter reaction time than previous electrochemical methods
[139]. The nanocomposite detected BPA in milk after extensive testing. Nanocomposites have reduced oxidation potential, higher sensitivity, lower detection limits,
and faster reactions [83,84].
Carbon sp2 hybridized 3D hexagonal dendrimer-carbon-nanotube hybrid CNTs.
CNTs are intriguing nanomaterials with pharmacological and biological applications, but their dispersibility, hydrophobicity, degradability, and toxicity limit clinical usage. Functionalization and hybrid nanocarriers are being studied to overcome
CNT limitations [140]. CNTs are suitable biosensors and biocatalysts, but their low
dispersibility in solvents, especially water, is an issue. Partial oxidation, hydrophilic
groups, and polymers improve CNT water dispersibility. CNTs were conjugated with
dendrimers to improve water dispersibility [114].
Multiwall nanotube mats were synthesized by dendrimer-aided catalytic annealing in air. Dendrimers affect nanober size. Dendrimer-based Co32 nanoclusters
were employed as uniform-size catalytic probes for diameter-controlled SWCNT
production. Topographical studies showed that the nanotubes had a restricted diameter range and were no thicker than 1.3 nm [141]. Dendrimer-CNT hybrids also used
innovative methods. Enzyme immobilization generated unknown dendrimer-CNT
hybrids. Bienzymatic CNT-PAMAM dendrimer conjugate immobilized GOx and
HRP primed—glucose-sensitive conjugate. The bienzymatic conjugate’s 0.34 V
negative potential allows glucose monitoring without ascorbic acid. Fluoroalkyls
have better thermal and chemical stability than water dispersibility, surface energy,
and dielectric constant. Fluorinated-dendrimer copolymer self-aggregates, making
220 Carbon-Based Nanocarriers for Drug Delivery
water dispersibility high. Copolymers spread SWCNTs and fullerenes in water at
21.5–67.3 and 4.2–13.3 µg/mL. In uorinated-dendrimer copolymer, SWCNTs,
fullerene, and MNPs improve aqueous dispersibility [142]. Electropolymerized polypyrrole lm served as a hybrid self-aggregation probe by self-assembling glutamate
dehydrogenase (GLDH) and poly(amidoamine) dendrimer-encapsulated platinum
NPs (Pt-DENs) onto multiwall CNTs. Anano bioconjugated biosensor evaluated
glutamate-oxidized NADH with high sensitivity, low detection limit, quick response,
and no interference. CNTs had equally spaced 3 nm-wide NPs. Biosensor response
depends on polypyrrole layer thickness, which increased with electro-polymerization
but lost biostability after six cycles [143]. The self-assembly of dendrimerencapsulated PtNP (Pt-PAMAM) and glutamate dehydrogenase (GLDH) on multiwall CNTs developed the rst amperometric glutamate biosensor (MWCNTs). CNTs’
GLDH-Pt-PAMAM multilayer enhanced electron transport surface area. GLDH
polyanionic material was used to make LbL lm at pH 7.4.10 nm thick CNT layer.
Repeatable, stable, and sensitive modied enzymatic biosensors prevent enzyme
leakage and maintain enzyme activity [65]. MWCNTs and pure dendrimers lost 38%
cytotoxicity. Grafting silver nanoparticles (AgNPs) boosts CNT-dendrimer hybrid
stability, water dispersibility, and antibacterial activity [144]. CNT-dendrimer hybrids
can be used in electrochemistry, while PAMAM G4 dendrimer templates PdNPs on
MWNTs. The nanocomposite converted hydrazine, a direct fuel cell fuel, electrocatalytically [145]. Most of the published research describes the synthesis of dendrimerCNT hybrids to achieve the greater dispersibility of CNTs in the aqueous phase.
Microspheres are protein or synthetic polymer powders with biodegradable nanocarriers and diameters < 200 m. Controlled and prolonged medicine distribution
requires microsphere delivery. Microspheres are nanocarriers too. Drug accumulation rather than other organs or tissue protects unstable drugs in the circulatory
system with microspheres. Hybrid dendrimer-microsphere carriers can bioengineer,
biocatalyze, and detect biomolecules [146]. Hybrid dendrimer-microsphere systems
are understudied. Microsphere-dendrimer glucose biosensors are noninvasive. Concanavaline A-glycodendrimer in biocompatible PEG microspheres is a minimally
invasive glucose sensor. PEG hydrogel matrix microporation generated microspheres. Throughout 14 days, the uorescent tag Con Ameasures physiological glucose levels via competitive binding. Leaching prevented pores from functioning and
reversing [147].
Bioengineering and catalysis employ dendrimer-microsphere hybrids. Since PLLA
hydrolyzes fast, dendrimer-like copolymers of poly(l-lactide) and polystyrene make
biocatalysis and bioengineering microspheres. Once hydrolyzed micromolecules and
solvents evaporated, 295 nm microspheres had one or two tiny surface holes [148].
Polystyrene microspheres stabilize PAMAM dendrimer, NPs coated in SiO2 for
immobilization and the nanocomposite. PAMAM (G5) dendrimer was grafted onto
polystyrene microspheres and dispersed in AgNO3 to form AgNPs. PS@PAMAM@
SiO2-Ag nanocomposite reduced 4-nitrophenol better in the catalytic column [149].
Dendrimers and microspheres may absorb hazardous chemicals from aqueous solutions. Stepwise reaction with methylate acrylate and ethylene diamine produced
magnetic poly-(methyl acrylate-divinyl benzene) microspheres on NH2-terminated
dendrimers. Nanohybrids absorbed aqueous hexavalent chromium. Due to several
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surface functions, a suitable pH of 3, and rising temperature, G3 adsorption was
231.8 mg/g [150]. Dendrimer-microsphere hybrids were largely employed for bioengineering and catalysis, not medication delivery.
Gelation creates pharmaceutical and biological hydrogels. Hydrogels with amphiphilic Janus dendrimers increased payload and drug release [151]. Wróblewska and
Winnicka found that PAMAM dendrimer-based erythromycin hydrogels released
erythromycin faster in a concentration- and generation-dependent way. Erythromycin release increased, and non-Newtonian thixotropic systems shear-thinned in rheograms. Later dendrimers’ bactericidal activity increased somewhat with stability at
40 ± 2 °C and 75 ± 5% RH [152]. Dendrimers were changed with integrin-binding
sequences, pN-modied hyaluronan, and propargylamine-derived azido-hyaluronic
acid to generate hydrogels. Dendrimers were thermoresponsive biological carriers
and did not affect hyaluronan hydrogel rheology [153].
With their 3D hyperbranched macromolecular architecture, precise molecular
weight, size, and shape, and excellent host-guest interactions conferred by a large
number of cavities in the internal structure and the presence of multifunctional surface groups, dendrimers are emerging as promising nanomaterials in the delivery of
drug and genetic material. These tiny macromolecules are getting a lot of attention
as potential nanocarriers with a wide variety of applications because of their unique
physical and chemical characteristics. Dendrimers have several potential benets as
drug carriers, but their toxicity due to their surface cationic charge and plush price
have limited their clinical usage. Thus, hybrid carrier systems constructed with dendrimers and other nanomaterials are being studied as a means to lessen these issues
and guarantee clinical applicability. One promising approach being investigated in
the realm of nanomedicine is the creation of hybrid nanomaterials for the transportation of bioactives. Dendrimers have recently been described in the literature as being
used in hybrids with other nanocarriers to increase medication delivery.
8.3 PROPERTIES OF NANOHYBRIDS
Composites combine two or more elements to create a material with superior properties than those of its constituent parts. This type of material typically consists of a
reinforcement to add stiffness and strength and a matrix to add geometry and cohesion. According to the intended use, we provide a wide variety of organic, metallic, polymeric, and ceramic matrices. Popular reinforcements include carbon bers,
glass, natural bers, and others. As these materials are sourced from the natural
world, they represent a sizable subset of the composite materials that we have available. Examples of these kinds of natural composites are bone and wood. Wood comprises a lignin matrix and cellulose bers, whereas bone comprises collagen, which
serves as the matrix, and bers formed of a mineral called apatite [7].
According to this denition, a nanocomposite is a multiphase material in which
all the phases have sizes less than 10 nm. The idea behind this type of material is
to use building blocks on the nanoscale scale to create and produce materials with
improved properties [29].
Research into nanocomposites has increased dramatically after discovering that
graphene has desirable properties. Graphene’s two-dimensional structure endows it
222 Carbon-Based Nanocarriers for Drug Delivery
with a wide range of desirable properties, including mechanical strength, thermal
conductivity, and electrical conductivity. The advantageous features of graphene
have led to several attempts to integrate it into polymeric matrices. Graphene’s measured mechanical properties are Young’s modulus of 1.0 TPa, a tensile strength of
42 N/m, and fracture toughness of 4.0 0.6 MPa. These values are evidence of the
extraordinary durability of graphene. Graphene and its derivatives have the potential to enhance the performance of polymer nanocomposites when utilized as bers.
One example is offered by Cheng-An etal., who studied the effect of adding 20%
graphene to PVA lms to increase their strength [154]. The resultant material had a
tensile strength of 59.6 MPa, which is almost ve times that of pure PVA.
This dramatic improvement in mechanical properties can be attributed to the
strength of the matrix, the hydroxyl groups in the PVA, the hydroxyl groups in the
graphene, and the functionalities of the oxygen in the graphene, which resulted
in the formation of hydrogen bridges. Compared to traditional ways of producing
carbon-based nanomaterials, hydrothermal carbonization stands out as a more ecofriendly option for producing nanocomposites. Hydrothermal carbonization is not a
recent synthesis process, but it has become an essential technique for making hybrid
materials from carbon [7]. Hydrothermal carbonization is attractive because it allows
for producing a wide variety of hybrid and carbon nanostructures while being environmentally friendly, controllable, and scalable. CO2 sequestration, water purication, and catalysts are just a few of the many chemical industry applications for the
products of this process. Plant-based, animal-based, and mineral-based natural bers
are each classied separately. Plant bers generally comprise cellulose, whereas animal bers comprise proteins (hair, silk, wool). Throughout the past decade, scientists
have investigated using bers of natural origin as the primary building blocks for
nanomaterials because of their wide availability, low cost, recyclable nature, and
superior mechanical and chemical properties.
Nanocomposites used or aimed at the biological and food industries nowadays
often have antibacterial properties. This is because biomedical practitioners are
having trouble treating infected wounds and foods that have been preserved for
extended periods of time. While developing multicomponent nanocomposites, scientists focus on a wide range of active agents to provide antibacterial activity; some
metals, such as silver nanoparticles or zinc oxide nanoparticles, stand out in this
respect, as do specic transition metals like Cu [155]. Although the inhibitory efcacy of antimicrobial medicines varies depending on the bacteria they are intended
to combat, different natural extracts have been used to offer these qualities to nanocomposites [156].
To produce chitosan-based nanocomposite lms with various clay loadings of
0, 5, 10, and 15% cross-linked with glycerol at concentrations of 10, 20, and 30%,
respectively, Kusmono etal. 2019 reported using a casting procedure [157]. The study
proved that incorporating clay into nanocomposites signicantly increased their tensile strength and tensile modulus, from 5% to 20%, respectively. Nevertheless, no
nanocomposite produced inhibitory zones against E. coli just by touch, ruling it out
as a practical possibility for use in packaging material [157].
Cell viability and biocompatibility studies showed no cytotoxicity in NIH3T3
or MG-63 cells. Astudy on the development of porous 3D scaffolds utilizing the
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freeze-drying approach based on gallium-apatite/chitin/pectin was reported by Cui
etal. [158]. The cells also grew in number and stuck to the scaffolds. Implantation
of the scaffolds showed the creation of mature bone via the generation of new bone
layers and the differentiation of osteoblasts; therefore, it is regarded as a material that
ts the conditions to be considered for orthopedic applications.
Nazir et al. produced a hydrogel nanocomposite composed of arabinoxylan
(ARA) and loaded with graphene oxide functionalized with the chemotherapeutic
medication uorouracil (5FU) [159]. According to the study, many types of bacteria,
including S. aureus and P. aeruginosa, and the skin cancer cell line U-87 were killed
by it. This has led to their classication as a promising nanomaterial for treating and
preventing skin cancer [159].
In 2022, Li et al. developed polyurethane foams that were both exible and
infused with Cu nanoparticles with a size distribution of 100 to 130 nm [160].
Researchers found that the addition of nanoparticles to polyurethane foam did not
alter the foam’s chemical makeup and that the foam exhibited potent antimicrobial
activity against a range of pathogens, including E. coli, P. aeruginosa, and S. aureus
[160]. This nding suggests the foam could nd application in water purication and
medicine.
Environmental pollution has emerged as a major problem worldwide due to the
devastating consequences of various pollutants on ecosystems and human health.
Thus, it is crucial for the world’s population that these poisons be treated and eventually eradicated. Contaminant removal by biodegradation is an adaptable process.
Nanocomposites with unique chemical and physical stability, large surface area, and
adsorption capacity can boost the efciency of biodegradation processes [161]. Biodegradation is believed to be a green process since it does not need additional energy,
thereby conserving both renewable and nonrenewable resources. Enzymatic, cellular, and bacterial breakdown are the principal areas of study [162].
In 2021, Candotto Carniel etal. studied the ambient biodegradation of graphene
using axenic cultures of basidiomycetes such Bjerkandera adusta, Phanerochaete
chrysosporium, and Morchella esculenta [163]. They report that the selected fungus
can oxidize graphene to a compound comparable to graphene oxide, and they recommend continuing the experiment for longer than four months to test if the product can
entirely degrade to CO
[163].
2
The chemical composition of the components determines the properties of natural
nanocomposites. Although natural polymers are notoriously abrasive and chemically
inert, they are exible and biodegradable. They frequently have antimicrobial and
bacteriostatic biological properties. However, several additives or llers are utilized
to improve their poor mechanical qualities, the most notable of which are metallic
nanoparticles, polymer nanoparticles, and carbon-based nanostructures, including
multiwall or single-wall carbon nanotubes, nanobers, graphene, fullerenes, etc. Natural composites are fascinating because they improve the natural polymer’s impressive characteristics. Natural inorganic nanocomposites containing zeolites, different
sands, feldspars, and clays combined with metallic nanoparticles or carbon-based
nanostructures are more challenging regarding breakdown or biodegradation. Nonetheless, positive characteristics like mechanical strength, corrosion resistance, hardness, etc. are present [7].
224 Carbon-Based Nanocarriers for Drug Delivery
8.4 APPLICATION OF NANOHYBRIDS IN DRUG DELIVERY
8.4.1 cancer Therapy
Problems with solubility and cell penetration are common when using chemotherapeutic drugs. The lack of specic therapeutic targeting for cancer cells further
restricts clinical uses by causing systemic toxicity [61]. The search for safe and efcient medication administration has become the forefront of scientic inquiry. The
potential of CNTs as a novel and developing nanomaterial for use in drug delivery
carriers has garnered considerable interest in recent years. Functionalized carbon
nanotubes delivered several tiny molecules of anticancer medication to tumor cells.
Several types of human cancer have been successfully treated with the chemotherapeutic drug doxorubicin (DOX). Branched PL-PEG functionalized SWCNTs
have had DOX loaded onto their sidewalls by π-π stacking [164]. The DOX loading ratio tested in this research was 2.5 g/g of SWCNTs. Unlike free DOX and
DOXIL, SWCNT-formulated DOX demonstrated signicantly higher therapeutic
effectiveness in a mouse breast cancer model while exhibiting signicantly reduced
toxicity. The same research team also used SWCNTs with paclitaxel loaded onto
them; they did this by attaching the medication to the amino group of the branching
phospholipid-PEG chains via cleavable ester linkages, which are hydrolyzed in the
cellular milieu [165]. The resulting substance, SWCNT-PEG-paclitaxel, is soluble in
water. In a 4T1 murine breast cancer model, the generated SWCNT-PTX conjugate
showed more efciency than clinical Taxol in reducing tumor development [166].
The SWCNT-PTX was also more blood-stable and less toxic than the control. The
anticancer prodrug cisplatin was conjugated to PL-PEG-SWCNT using a similar
method [167].
Peptide linkages were used to attach the amino end group of PL-PEG to the carbon nanotubes, where the platinum (IV) complex c,c,t-[Pt(NH
CH2CO2H)] was deposited. Endocytosis was used by testicular cancer cells to absorb
the SWCNTs, and a subsequent decrease in compartmental pH allowed for drug
release. In addition, toxicity was signicantly reduced in the SWCNT- formulated
platinum (IV) complex compared to the free drug therapy. SWCNTs conjugated with
quantum dots (QDs) or the targeting ligand epidermal growth factor (EGF) have
been used to provide targeted delivery of anticancer medicines like cisplatin to squamous carcinoma cells. As squamous carcinoma cells have EGF receptors, the QD
luminescence makes it easy to follow the SWCNT formulation, and the conjugation
of EGF shows that the formulation was quickly taken up [168]. SWCNTs have also
been investigated for their potential to transport small interfering RNAs (siRNAs)
through non-covalent interactions [169]. To suppress the expression of telomerase
reverse transcriptase (TERT) and to decrease cell proliferation in-vitro and in-vivo in
tumor models, a recent study investigated the capacity of cationic SWCNTs to form
stable complexes with siRNAs [170].
Using a 1,3-dipolar cycloaddition strategy, CNTs could be covalently functionalized with methotrexate (MTX). Two connecting sites, one for FITC and one for MTX,
were introduced onto the sidewalls of carbon nanotubes in this study’s protocol [171].
Increased cellular uptake of MTX was achieved by conjugation to carbon nanotubes. Nevertheless, neither the in-vitro nor the in-vivo effectiveness of the drugs nor
(OEt)(O2CCH2
3)2Cl2
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their release patterns were examined. The anticancer drug 10-hydroxycamptothecin
(HCPT) was given using an MWNT that had been covalently modied [172]. By
amidation, the carboxylic groups on the oxidized nanotube were linked to drug molecules using diaminotriethylene glycol as a spacer. The MWNT-HCPT conjugates had
a longer blood circulation and a larger drug accumulation at the tumor site, and the
MWNT-HCPT formed HCPT demonstrated better anticancer efcacy in-vitro and
in-vivo compared to the current HCPT formulation [61].
Using biocompatible polymeric membranes like alginate-poly-l-lysine- alginate
(APA), we microencapsulate carbon nanotubes for site-specic delivery [173].
Microencapsulation serves to shield payloads from hostile surroundings while letting targeted solutes through a polymeric membrane. The regulated, continuous, and
extended release of the therapeutics at the intended location allows for the optimal
delivery of bioactive compounds. To encapsulate the CNTs, a microencapsulator was
used to create beads out of a solution of calcium chloride and sodium alginate, which
had been mixed with a suspension of functionalized SWCNTs. During our early
research, we analyzed how the SWCNTs were dispersed throughout the polymeric
core. Using the results of optimization and characterization of the microencapsulated
SWCNT formulation, we are now concentrating on delivering the therapy to specic
areas in the gastrointestinal tracts of animals to treat colon cancer. Our lab coupled
SWCNTs to pEGFP in an in-vitro investigation of a colon cancer cell line to improve
transfection efciency while minimizing cellular damage [174].
8.4.2 neUroDegeneraTiVe Diseases
Neurodegenerative disease refers to a collection of disorders that affect the brain
and spinal cord and result in the malfunction or death of neurons. Alzheimer’s, Parkinson’s, and Huntington’s illnesses are the three most prevalent kinds of neurodegeneration, according to experts [175]. Alzheimer’s disease, the most frequent form
of dementia, is characterized by the neuroinammatory development of amyloid
plaques and neurobrillary tangles. Adecit in acetylcholine is another indication of
the condition [175]. Subcellular and molecular characteristics of NDs include faulty
synapses, neuronal loss, and the creation of cerebral deposits, all of which are produced by the accumulation of improperly folded proteins [176]. These mechanisms,
which contribute to cellular homeostasis, make it possible to prevent neurological
illnesses. Hence, monitoring ion levels and dynamics in the brain is a valuable tool
for analyzing and interpreting cerebral activity, giving a fresh way of considering and
tracking neurological illnesses such as Alzheimer’s [177]. For the treatment of neurodegenerative illnesses, medication delivery based on solid lipid nanoparticles should
be prioritized. Specically, SLNs can deliver the active component to the appropriate
location with minimal off-target effects, overcome physiological barriers to boost
bioavailability without the need for enormous dosages, and protect pharmaceuticals
against chemical and enzymatic degradation [178].
Alzheimer’s disease (AD) is a progressive, deadly neurological condition that
mostly affects the elderly and is the major cause of dementia in this group. AD is
characterized by diminished cholinergic transmission, which is notably evident in
the cerebral cortex and hippocampus, two brain areas associated with improved
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