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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5445_Библиотеки_им_академика_М_И_Перельмана.pdf
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experience diarrhea and rectal bleeding, which is typically exacerbated by chemo-
radiation. Many pelvic radiation patients use psyllium husk for diarrhea. In mice,
dietary ber supplementation improves tumor response and reduces radiation-
induced tissue damage. If veried in people, patient care would improve greatly.
Healthy participants will be studied to determine dietary ber processes and effects.
An inulin with or without psyllium within-subject diet intervention research on
healthy older individuals (>60 years old) will assess if a subgroup responds to
dietary ber modulation. They examine dietary ber’s physiological effects.
Participants received placebo, inulin, or psyllium plus inulin in random order (6
combinations) for 2weeks with 2-week washouts.
Baseline intestinal microbial activity, short chain fatty acid (SCFA) concentrations,
and habitual ber intake from dietary questionnaires/food diaries will be utilized to
identify those who may benet from dietary ber modication. Dietary ber supple-
mentation may raise SCFA levels and microbial abundance. Dietary factors, bacterial
abundance, and SCFA levels will affect plasma cytokines (Holmes et al. 2022).
Researchers created hybrid microparticles out of inulin and lipids and loaded
them with the antibiotic rifampicin. Scientists looked at how diseased macrophages
reacted to a pH-induced release of the drug. The ndings revealed the potential for
more effective therapy and tailored distribution. This study set out to develop a
method of administering medicine to macrophages that had taken up residence
within infected cells. Research that had previously been conducted on inulin-based
formulations for the treatment of cancer was analyzed by Eswara Naga Hanuma
Kumar Ghali and others. A review was conducted to explore the potential of inulin
as a medication carrier, as well as its capacity to function in a synergistic manner,
therefore impacting cellular signaling and the immune response in the context of the
battle against cancer (Ghali etal. 2024b).
Clinical investigations of inulin-containing medication formulations have shown
little evidence. Nonetheless, evidence from many studies on inulin microparticles—
and more especially Advax—as a vaccination adjuvant suggests that delta inulin
was safe and well-tolerated (Table16.2). The safety prole is unaffected and there
have been no reports of hazardous reactions. These inulin microparticles were safe
to employ in vaccination trials conducted on people. Its promising safety prole
makes it an attractive option for use as a vaccination adjuvant. The SARS-CoV-2
vaccine, also known as the COVID Vaccine, is entering human clinical trials soon
and uses inulin microparticles as an adjuvant (Petrovsky and Cooper 2015; Gordon
etal. 2012).
16.5 Future Perspectives
16.5.1 Emerging Trends andInnovations inInulin-Based
Drug Delivery
In the pharmaceutical innovations eld, inulin is developing a valuable and promis-
ing biopolymer for drug delivery applications. Enhanced drug bioavailability,
improved cellular uptake, and facilitated targeted, sustained, and controlled release
16 Potential ofInulin toRevolutionize Pharmaceutical Industries
358
of therapeutic agents can increase inulin’s effectiveness through the chemical mod-
ulation adaptation process. The exible backbone of inulin and the deciency of
sugar rings allow for various structural recongurations that enable the comprehen-
sive delivery of methods, such as hydrogels, conjugates, nanoparticles, and micelles,
which are also helpful in drug administration (Anjuomo etal. 2021b).
Due to inulin’s natural richness, biodegradability, and lack of toxicity, it is a better
option for synthetic polymers. Synthetic polymers may be unstable, need costly modi-
cation, and have poor biocompatibility. These advantages make inulin an outstand-
ing alternative (Koch etal. 1999). Inulin is picked from a variety of plants, including
chicory, dahlia, Jerusalem artichoke (Torres etal. 2019), vegetables, fruits, and grains,
including garlic, leeks, bananas, onions, and wheat (Mensink etal. 2015b), with a
linear chain of fructose units linked by β (2–1) glycosidic bonds. The chemical struc-
ture of inulin confers signicant exibility and versatility, and it is essential to develop
advanced drug delivery systems (Mensink etal. 2015b; Barclay etal. 2010).
The emerging and innovative technologies in inulin-based drug delivery systems
highlight their capabilities to address present challenges and improve therapeutic
success.
16.5.2 Enhancing Bioavailability andControlled Release
Drug release from a complex in controlled-release drug delivery systems is depen-
dent upon matrix swelling, matrix degradation, or drug release from the formula-
tion’s oleaginous portion. Inulin, due to its natural properties, can be a potential
candidate as a hydrophilic polymer in the preparation of a controlled-release system.
In fact, the control of drug release depends on several properties, among which solu-
bility and molecular weight are critical for the hydrophilic polymer. Inulin interacts
with water to form a swollen structure which provides adequate room to incorporate
drugs in the hydrated layer (Anjuomo etal. 2021a). The hydration, swelling propor-
tion, swelling behavior, propensity for chain relaxation, mechanical properties, bond
dissociation, etc. of inulin can be inuenced by the ne sugar structure and comparison
to many other polysaccharides that are stated as matrix forming materials used in the
preparation of a controlled-release system. Akhgari etal. (2006) investigated the
potential of inulin as a coating system and its effectiveness in controlled medication
release. Polymethacrylates (Eudragit) with and without inulin were used to assess
drug permeability in colonic medium, swelling tests, and water vapor transfer assays.
The media’s pH regulated medication release when inulin polymers were not present.
Compared to pH-dependent polymers, the inulin- dependent method showed more
drug swelling and penetration (Akhgari etal. 2006).
Drugs with poor solubility in water have low bioavailability and provide a chal-
lenge to effective drug administration. A combination of inulin and poly (acrylic
acid) grafted inulin was used to create tablets of Irbesartan, a medication that is not
very water soluble. The drug’s solubility was enhanced by the presence of inulin
ower-shaped platelets that encircled it. The solubility of the medication was shown
to increase when the concentration of inulin grew (Fares etal. 2011).
P. M. Guptha et al.
359
16.5.3 Development ofNanoparticles andMicelles
The critical aggregation concentration (CAC) is the point at which the inulin begins
to form nanoparticles. It is the reaction temperature that has an effect on both the
CAC and the size of the nanoparticles. The nanoparticles of inulin do not pose a
threat to the mononuclear cells found in the peripheral circulation (Dan and
Moulik 2009).
Inulin can exist on the outside of the forming nanostructure or in the inner core,
or it can be embedded into or conjugated with the polymer chains. The mode and
preparation methods are strongly dependent on the properties of inulin and the
selected polymer and, in some cases, the model drug. The pharmaceutical applica-
tions of inulin may open up new opportunities in nanostructures. The study on the
application of inulin into nanostructure will become a hot issue in the future,
especially in the stimulation-responsive behavior, site-targeted tradition, and
invivo behavior and the regulation of the biodistribution of the nanostructures.
The inulin- based nanostructures can occur from simple physical mixing or self-
assembly to grafting or complex chemical bonding interaction (Jiménez-Sánchez
etal. 2019a).
16.5.4 Prodrug Formation andTargeted Delivery
When compared to other biodegradable polysaccharides, inulin is an effective
drug delivery carrier due to its distinctive and adaptable structure, its ability to
stabilize and protect, and its capacity to target specic organs. Each fructose unit
has three hydroxyl groups linked to it, and these groups act as an anchor for the
chemical alteration process. On the other hand, IN derivatives could represent a
novel approach to medication delivery that targets the kidney. In order to verify
the theory, ferulic acid (FeA) was converted into inulin (IN) by the formation of
an ester link and an amide bond, with ethylenediamine serving as the spacer (Chen
et al. 2020). As a consequence, two FeA-IN conjugations were formed: inulin
ethylenediamine ferulate (IN-FeA) and inulin ferulate (IN-FeA). Conjugations
were characterized via NMR spectroscopy. FeA in vitro release patterns were
assessed in renal homogenate and mouse plasma. Lastly, renal-targeting skills
were evaluated using the biodistribution test. FeA release for IN-FeA and
IN-EDA-FeA was higher in renal homogenate than in mouse plasma, indicating
that the conjugates are stable in plasma and more likely to release in the kidney.
IN has weak binding afnity to plasmatic proteins, but it performs well in kidneys
and may reach large concentrations after intravenous injection (Feher 2017), mak-
ing it a viable prospective renal- targeting drug carrier. Recently, the modication
and derivatization of IN has been effectively used to generate several novel drug
delivery systems such as nanoparticles, macromolecular bioconjugates, and
micelles.
Inulin has a few unique properties, such as not being hydrolyzed by stomach or
intestinal contents alone, being fermented effectively by bacteria in the colon, and,
16 Potential ofInulin toRevolutionize Pharmaceutical Industries
360
under specic conditions, producing high quantities of propionic and butyric acids
during fermentation. Therefore, inulin is being considered for use in prodrugs and
drug delivery systems; this means that it can do more than only act as a matrix for
drug loading and release; it can also be coupled with a cytoprotectant and a drug,
allowing for targeted release in the colon (Sheng etal. 2023).
16.5.5 Inulin-Coated SPIONs forCancer Therapy
Inulin is used as efcient stabilizers and crosslinking intermediates in the synthesis
of gold and silver nanoparticles. To enhance the excretion and prolong the circula-
tion time of gadolinium, inulin-coated gadolinium oxide nanoparticles exhibit
improved biodistribution. The inulin coating may improve super paramagnetic iron
oxide nanoparticles (SPION) stability and reduce interaction with macrophages,
thus providing a means for further invivo application (Kermanian etal. 2021).
The promising anticancer activity of inulin-coated SPIONs, detected invitro in
NIH/3T3 and 4T1 cell-based models (Aram etal. 2022) and via MRI, relative to
their pristine counterparts and dimercaptosuccinic acid-coated SPIONs, would
facilitate the translational development of such agents to the clinic in as short a time
as possible for practical application. The inulin-coated superparamagnetic ferric
oxide nanoparticles (Kermanian etal. 2021) (ICS-SPIONs) were on average size of
80 nm, possessed superparamagnetic dipole-dipole collision interaction, and
showed high dispersibility in both the water solvent and culture medium. The
nanoparticles immediately reached the maximum temperature in the alternating
magnetic eld (AMF) system for both hyperthermia and conventional thermal ther-
apy. Furthermore, the designed ICS-SPIONs were not cytotoxic to the murine breast
4T1 cancer cells, and the primary cancer cells presented a lesser effect compared to
the 4T1 cancer cells. Accordingly, the inulin-coated SPIONs could be a new and
promising ThermoSeed in breast cancer therapy (BCT) with a simple synthesis and
surface functionalization. It envisages the future application of modied multifunc-
tional SPIONs in MRI for potential patient selection before magnetic hyperthermia
alone, feasible systemic administration for cancer diagnosis, effective therapy, and
response assessment.
16.5.6 Hydrogels forSustained Drug Delivery
Hydrogel is a three-dimensional (3D) network that can enlarge and retain a substan-
tial quantity of water or physiological uid without disintegrating, derived from
hydrophilic polymers. Hydrogels keep their structure because individual polymers
are cross-linked chemically or physically. Given its remarkable biocompatibility,
biodegradation, high-loading capacity, and physiological activity resemblance to
natural tissues, hydrogel is becoming a more and more popular biomaterial among
the delivery methods and carriers now in use (Stella and Nti-Addae 2007). Hydrogels
may be produced through the utilization of either natural or synthetic polymers.
P. M. Guptha et al.
361
Hydrogels are composed of natural polysaccharides, including inulin, pectin, chito-
san, hyaluronic acid, alginate, starch, gelatin, pullulan, dextran, and guar gum
(Tripodo etal. 2015).
It is possible to customize drug delivery to specic tissues by adjusting many
factors during the hydrogel manufacturing process. These parameters include
swelling behavior, crosslinking density, mesh size, permeability, mechanical
strength, and drug release. Modifying inulin creates stable drug delivery hydrogels
with appropriate physicochemical features. Free radical polymerization of aqueous
solutions of methacrylic anhydride or glycidyl methacrylates modied inulin, radi-
cal copolymerization, grafting polymerization, Michael addition crosslinking, UV
radiation, chemical crosslinkers, and enzymatic methods have been used to make
inulin hydrogels. A stiff hydrophobic area in the inulin hydrogel was created by
crosslinking methacrylated inulin with aromatic azo agent bis (methacryloyl-
amino) azobenzene (BMAAB) (Maris etal. 2001). In vitro release studies from
pH-sensitive inulin hydrogels for targeted colon delivery showed that inulin could
protect drugs from degradation in the upper GIT, particularly in the stomach and
intestine, and allow drug release in the colon. Complex diffusion, swelling, and
chemically regulated release processes are thought to release active medicines
from inulin hydrogel. Hydrogel biomaterials must be removed from the body fol-
lowing drug administration. Biodegradability is required for human hydrogel
usage. The kind and cleavage of polymer network bonds and how polymers are
linked can affect inulin hydrogel breakdown. Inulin is an intriguing polymer for
colon targeting because colonic microorganisms degrade its glycosidic bonds site-
specically (Anjuomo et al. 2021b). Inulinase or cecal contents should be
employed to study the degradation of modied inulin derivatives used to make
hydrogels.
16.5.7 Combining Inulin withOther Technologies
forSynergistic Effects
Sukirti Joshi etal. examined the rheological, structural, color, and molecular inter-
actions produced in heat-desiccated milk semi-solids (HDMS) using hot melt extru-
sion 3D printing. They nd that high intensity ultrasound (HIUS) treatment at 200,
400, and 600W, along with inulin addition at 0, 2, and 4% w/w, has a synergistic
effect on HDMS restructuring. Extrudability, viscoelastic behavior, and non-
Newtonian pseudoplasticity were all enhanced by the combination of HIUS and
inulin, according to the results (Table16.4). Milk protein and inulin formed a robust
cross-linked network as a consequence of the synergistic effects of inulin addition
and HIUS-induced exposure of hydrophilic groups and creation of new hydrogen
bonds (Joshi etal. 2023).
Marion Regnier etal. found that a combination of inulin and rhubarb prevented
weight gain, fat storage, and many metabolic disorders linked to obesity when taken
in supplement form in response to a high-fat, high-sucrose (HFHS) diet. Energy
expenditure went up, brown adipose tissue did not whiten as much, mitochondria
16 Potential ofInulin toRevolutionize Pharmaceutical Industries
362
Table 16.4 Synergistic technologies: combining inulin with other drug delivery methods
Combination
Mechanism Benets Target diseases
Potential
limitations
Reference
Inulin with
hydrogels
Polymer
network
formation
Sustained release,
biocompatibility
Wound healing,
tissue
regeneration
Stability
challenges
Sharpe
etal.
(2014)
Inulin with
micelles
Self-assembly
of
amphiphilic
molecules
Enhanced
solubility,
specicity
Cancer, gene
therapy
Stability
issues
Kesharwani
etal.
(2019)
Inulin with
liposomes
Lipid bilayer
encapsulation
Targeted delivery,
reduced toxicity
Vaccines, gene
therapy
High
production
costs
Xue etal.
(2022b)
Inulin with
nanoparticles
Nano-coating Controlled-
release, improved
targeting
Cancer, genetic
disorders
Potential
toxicity
Scialabba
etal.
(2017)
Inulin with
solid
dispersions
Drug
dispersion in
solid matrix
Improved
bioavailability,
stability
Oral drug
delivery
Formulation
complexity
Visser etal.
(2010b)
Inulin and
β-cyclodextrin
Chemical
conjugation to
form INUCD
Solubilizes
hydrophobic
drugs, colon-
specic release
Inammatory
bowel disease
(IBD), colon
cancer
Stability and
drug release
control
Catenacci
etal.
(2020)
Inulin and
Eudragit RS
Single-layer
coating with
CCD design
Sustained,
targeted drug
release
Crohn’s
disease,
ulcerative
colitis
Microbial
degradation,
pH
sensitivity
Soltani
etal.
(2023)
were busier, and white adipose tissue expressed more lipolytic markers. While
either inulin or rhubarb alone may alter the makeup of gut microbiota and bile acids,
the synergistic effect of the two is small. On the other hand, inulin and rhubarb
together seemed to strengthen the intestinal barrier, as they both raised the number
of goblet cells and the production of several antimicrobial peptides (Régnier
etal. 2023).
16.6 Future Aspect andConclusion
As a result of advances in biotechnology and data-rich environments, personalized
medicine (PM) has the potential to include medicines and interventions tailored to
certain patient types in the future. One potentially game-changing method for medi-
cation delivery systems is the use of inulin, a polysaccharide found in many plants
(Fig.16.2).
When designing personalized medication delivery systems, inulin is a great
choice due to its biocompatibility and versatility. For project management methods,
these characteristics could be vital. The ability to produce hydrogels that can
respond to physiological variables, such as changes in pH, allows for the
P. M. Guptha et al.
363
Fig. 16.2 Emerging trends in inulin-based drug delivery
administration of medicine to certain parts of the gastrointestinal system, such as
the colon. By leveraging the site-specic inulin breakdown by the colonic microbi-
ota, this characteristic is particularly effective for pharmaceutical distribution to
specic parts of the colon (Wong etal. 2017; Jiménez-Sánchez etal. 2019a).
We may learn more about the possible health impacts of dietary bers and other
physiologically active substances from research on inulin’s effects on cholesterol
and its capacity to trigger inammation at high dosages. Customized nutrition, an
essential part of personalized therapy, requires this data (Chiu etal. 2002).
The widespread use of electronic health records (EHRs) and wearable devices
facilitates the continuous and real-time monitoring of health parameters. This tech-
nological advancement and the extensive collection of personal health data lead to
a more personalized healthcare intervention. Patient stratication and the building
of unique proles may be accomplished by using vast amounts of regular healthcare
data for research, which enables customized clinical trials and the quick integration
of study ndings into clinical practice (Stella and Nti-Addae 2007).
In summary, inulin’s role in the future of personalized medicine extends beyond
its direct health benets. It exemplies how natural compounds can be harnessed in
sophisticated drug delivery systems, contributing to the individualization of
16 Potential ofInulin toRevolutionize Pharmaceutical Industries
364
Table 16.3 Emerging trends in inulin-based drug delivery innovations
Innovation
Description Advantages Challenges Applications
Reference
Hydrogels 3D polymer
networks
Controlled
release
Stability
issues
Wound
healing, tissue
engineering,
drug delivery
Sharpe etal.
(2014),
Peppas etal.
(2000),
Palumbo
etal. (2015)
Micelles Nano-sized
spheres
Enhanced
solubility
Stability Cancer
therapy, gene
delivery,
diagnostic
imaging
Ferreira
etal. (2002)
Liposomes Lipid
bilayers
Targeted
delivery
Costly Cancer
therapy,
vaccine
delivery, gene
therapy
Xue etal.
(2022b)
Prodrugs/
conjugates
Drug
conjugation
Improved
bioavailability
Synthesis
complexity
Cancer
therapy,
chronic disease
management
Anjuomo
etal.
(2021b)
Inulin
complex/
chelating
agents
Drug
complexes
Enhanced
stability
Formulation
complexity
Cancer
therapy,
infection
control,
chronic disease
management
Pitarresi
etal. (2008)
Microparticles Small
particles
Targeted
delivery
Production
complexity
Cancer
therapy,
vaccine
delivery,
chronic disease
management
Saud etal.
(2023)
Nanoparticles Nano-sized
particles
Controlled
release
Toxicity Cancer
therapy, gene
delivery,
diagnostic
imaging
Jiménez-
Sánchez
etal.
(2019b)
Solid
dispersion
Solid drug
matrix
Improved
dissolution
Stability
issues
Oral drug
delivery,
chronic disease
management
Visser etal.
(2010a)
treatment strategies. As personalized medicine evolves, the focus will increasingly
shift towards prevention, risk denition, and optimizing health promotion strate-
gies, with insulin playing a signicant role in this transformation.
Table 16.3 shows the key areas where inulin is making signicant contributions
to drug delivery technologies, reecting its versatility and potential as a biocompat-
ible and biodegradable material for future pharmaceutical applications.
P. M. Guptha et al.
365
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