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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5445_Библиотеки_им_академика_М_И_Перельмана.pdf
56
Inulin based
drug delivery
systems
Fig. 3.1 Inulin-based drug delivery systems
Although it is used in several sectors, inulin is most commonly found in the food
industry (Bhanja etal. 2022; Jackson etal. 2022; Sharma etal. 2022). It is being
researched to use chemically altered inulin in cosmetic compositions. As a moistur-
izing agent, carboxymethyl or quaternized inulin can replace hyaluronic acid
(Bhanja etal. 2022; Akram etal. 2019b). For use as an emulsier in antiaging com-
ponent formulations as well as personal care and cosmetic uses, hydrophobically
modied inulin is a good choice (Yang etal. 2023). Inulin-rich materials are typi-
cally employed in industrial biotechnology to produce biofuel (Singh etal. 2022).
3.2.1 Types ofDrugs Suitable forInulin Encapsulation
In the last 10years, inulin has been used in micro- and nanoscale. Pediococcus aci-
dilactici may create pediocin when given natural or hydrophobically altered inulin
particles, which can then be used as nanostructured prebiotics in a variety of bio-
logical activities (Jiménez-Sánchez et al. 2019; Sharma and Tailang 2020).
Conversely, inulin may be employed either by itself or in combination with different
biopolymers for a wall material for the creation of bioactive component encapsulat-
ing and delivery systems. Other terms that are employed in the context of “wall
material” are matrices, carrier, cover-up, and encapsulant. Through the
P. Sharma et al.
57
encapsulation procedure, the bioactive material may be shielded from unfavorable
environmental factors. Encapsulation can also guarantee the regulated release of
bioactive compounds and enhance their physicochemical and biological character-
istics. The applications of the micro- and nanoencapsulated bioactive materials span
a number of industries, including agrochemistry, pharmaceuticals, and food (An
etal. 2024; Gruskiene etal. 2024; Sharma 2021; Amiri etal. 2024).
In addition, a large number of encapsulating active compounds, such as antifun-
gal/antiparasitic (amphotericin), hormonal (leuprolide), anticancer (doxorubicin
(DOX), vincristine, paclitaxel (PTX)), or analgesia therapies (morphine), have
recently been launched in the pharmaceutical sector (Rivas etal. 2017). In the realm
of medicine, encapsulating active molecules is not limited to the application of bio-
polymers or synthetic polymers. Novel strategies have been documented, such as
the utilization of erythrocytes as medication “capsules” (Ge et al. 2018).
Encapsulating medications for anticancer treatments (Alhajamee etal. 2022) and
using nanoparticles (Kim etal. 2019; Sharma etal. 2021) have garnered a lot of
attention throughout the past 10years.
3.2.2 Techniques forFormulating Inulin-Based Drug Carriers
Depending on the purpose of the usage, a variety of techniques can be employed to
prepare encapsulated medicines. The most common methods for encapsulating sen-
sitive medications (pharmaceuticals), sensitive dietary supplements, etc. are spray-
drying and freeze-drying. Low temperatures and a liquid feed that turns into powder
in a single step are the primary benets. The ability to dissolve powders generated
by spray-drying that include encapsulated sensitive chemicals is insufcient for
medication delivery. This is the primary justication for the technique’s usage in the
production of inhaled medications (Kandasamy and Naveen 2022; Pankaj etal.
2015). In recent years, a novel and distinct method for applying a powder layer to
capsules has been employed. The enhanced tuning of the regulated release of the
encapsulated drug is made possible by the extra coating of powder (Jing etal. 2022).
The latter stages in the manufacturing procedure for many of these products (drugs,
dietary supplements) include spray-drying and (spray) freeze-drying methods.
Nevertheless, other processes, including combining with other ingredients (fats, liq-
uid matrix structures, etc.), heating, etc., may be involved in the production of use-
ful meals. Dairy products, juices, baked goods, etc. are the primary areas of
nutritional usage (Oliveira etal. 2021). Figure3.2 gives a summary of the most
popular encapsulation systems and techniques.
3.3 Real-Time Formulations ofInulin
By shielding the encapsulated medication from the stomach’s acidic environment
and permitting its breakdown in the colon when colonic microbiota (Castelli etal.
2008) is present, inulin delivers regulated release of medicines to the colon.
3 Inulin: AVersatile Polymer forDrug Delivery System
58
Mixing
homogenization
Microfluidic
techni
q
ues
Microencapsulation
Additional coating
Freeze drying
Spray drying Particles
Fig. 3.2 The most common techniques for formulating inulin-based drug carriers
Twenty- four swelling tests, water vapor transmission tests, and an evaluation of
drug permeability in colonic medium using polymethacrylates (eudragit) with and
without inulin were used to assess the possibility of inulin as a coating system and
its efcacy in controlled drug release. If inulin polymers were not present, the
media’s pH would regulate medication release. Comparing the pH-dependent poly-
mers to the inulin-dependent system, greater drug penetration and swelling behav-
ior were discovered (Akhgari etal. 2006). Drugs with limited water solubility pose
a challenge to effective drug delivery because of their partial solubility, which
results in low bioavailability (Sharma and Tailang 2022). To make irbesartan tablets,
inulin and poly (acrylic acid) grafted inulin were combined. The drug’s breakdown
was then accelerated by the inulin’s ower-like platelets that surrounded it. The
drug’s solubility was enhanced by a rise in inulin content (Fares and Khanfar 2011).
For the solubilization and encapsulation of medications (Dan etal. 2009a), the abil-
ity of inulin to form aggregation in various solutions, such as Dimethyl Sulfoxide
(DMSO), water, CHAPS (3-[(3-cholamidopropyl) dimethylammonio]-1-propane-
sulfonate), and CnTAB (cetyl trimethylammonium bromides) might be helpful. At
different concentrations of CnTAB and inulin, the physicochemical relationship
between cationic amphiphilic surfactants of different alkyl chain lengths was inves-
tigated. Up to a reasonable concentration of amphiphile, it has been shown that
raising the amount of alkyl groups strengthens the inulin aggregation. The amphi-
phile generated free micelles at extremely high levels (Dan etal. 2009b). Another
report on inulin inclusion in a three-layer coat technique comes from Ravi etal.
(2008). The medication diltiazem HCl was encapsulated in a guar gum and chitosan
tablet. The exterior coating of shellac and the interior layer of inulin surrounded this
tablet. The purpose of the inner and outermost coating, accordingly, was to defend
from the intestinal and stomach environments. Next, when the other two polysac-
charides broke down, the medication was released into the colon (Ravi and Kumar
2008; Sharma etal. 2023a).
P. Sharma et al.
59
3.3.1 Inulin-Based Hydrogels
A hydrogel is a three-dimensional (3D) matrix made of hydrophilic polymers that
have the ability to expand and retain a signicant volume of physiologic uids or
moisture without disintegrating (Sharma and Jain 2023). The physical or chemical
cross-linking between distinct polymers is what keeps hydrogels structurally stable.
Because of hydrogel’s remarkable biological compatibility, biological degradation,
high-carrying capacity, and physiologically active resemblance to natural tissues,
the demand for using it as a biomaterial is expanding quickly among the readily
accessible delivery systems and carriers (Tian etal. 2020). Polymers that are syn-
thetic or natural can be used to fabricate hydrogels. Hydrogel-forming polysaccha-
rides include natural polysaccharides like pullulan, guar gum, dextran, hyaluronic
acid, inulin, chitosan, and alginate (Hamedi etal. 2018).
Additionally, Anjuomo etal. (2019a) described creating innovative injectable
inulin hydrogels without the need of an activator or starter by combining oxidized
inulin using adipic acid dihydrazide to serve as cross-linker. The hydrogels are cre-
ated by Schiff base interactions involving oxidized inulin and adipic acid dihydra-
zide. In this instance, relative to the normal pH level, the drug-loaded hydrogel
exhibits increased invitro dissolution of 5FU at an acidic pH.In a sodium bis(2-
ethylhexyl) sulfosuccinate (AOT) reversed microemulsion, inulin hydrogels are
also created via a Michael-mediated cross-linking process involving linear inulin
and additional crosslinking substance, divinyl sulfone (DVS) (Sahiner etal. 2014).
The aforementioned research makes it abundantly evident that several chemical
strategies have been developed for the manufacture of inulin hydrogel (Sharma 2022).
3.3.2 Inulin-Based Micelles
Polymeric micelles (PMs) have garnered signicant interest in the last 20years as a
exible nanotechnology-based drug delivery system for medicines with low water
solubility (Cho etal. 2015). Signicant advancements in bioavailability and solubil-
ity are achieved when medications with little solubility in water are encapsulated
within the hydrophobic center of PMs. A hydrophobic core encircled by a hydro-
philic shell makes up PMs, which are self-assembling core-shell nanostructures cre-
ated in an aqueous solution (Mandracchia etal. 2016). The increased permeability
and retention phenomenon is partially responsible for the buildup of PMs into dis-
eased tissues, including tumors and infracts having leaky vasculature, due to their
tiny size, which ranges from 10 to 100nm (Sharma and Tailang 2017).
Celecoxib and curcumin, two medications that are very hydrophobic and weakly
soluble in water, were shown to become more soluble in inulin micelles, according
to the investigators’ research (Sharma and Tailang 2017). The application of nano-
micelles improved the release and cellular absorption of curcumin into the malig-
nant cell. Moreover, micellar systems can be employed to administer various
medications. For example, altered inulin functionalized using vitamin E micelles
was created by Tripodo etal. (2019) to effectively distribute rifampicin for the
3 Inulin: AVersatile Polymer forDrug Delivery System
60
management of mycobacterium TB infections. Rifampicin (RIF)-delivering
micelles were produced by Tripodo etal. using inulin functionalized with vitamin E
(INVITE) and its succinylated derivative (INVITESA), which showed comparable
antibacterial activity against gram-positive bacteria and strong mucoadhesion to
mucin (Tripodo etal. 2019).
In a different work, a new amphiphilic inulin copolymer called INU-ED-RA was
created by partially functionalizing the hydroxyl moiety of the inulin utilizing eth-
ylenediamine (EDA) and then attaching retinoic acid (RA) to the INU-ED via an
amide bond employing carbodiimide chemistry (Di Prima etal. 2017). In a solution
of water having particle sizes below 500nm, the hydrophobic copolymer self-
assembles to form persistent micelles. It is being utilized to the encapsulating of
corticosteroids, including dexamethasone, triamcinolone, and triamcinolone ace-
tonide (Di Prima etal. 2017; Sharma etal. 2017).
3.3.3 Inulin-Based Liposomes
Liposomes are lipid-based drug delivery vehicles having the capacity to enclose
their water-based interior by self-associating into bilayers. Liposomes have a num-
ber of benets, such as avoiding instability, barriers to cell and tissue absorption,
insufcient bioavailability, and inadequate in vivo drug biodistribution at the
intended site (Sercombe etal. 2015). Yet, because of their enormous size of particles
in the 500–5000nm range, the traditional kind of liposomes presents a challenge for
the reticuloendothelial system (RES) to recognize and degrade, in addition to an
absence of selectivity when used as a means of delivering drugs in clinical practice
(Mufamadi etal. 2011).
Innovative methods have been developed to enhance the liposome medication
delivery system, including the use of smaller components (micro- to nanosized
scale) and modifying their surfaces employing multifunction carriers (Hua and Wu
2013; Sharma 2023). The medication was more precisely delivered to target areas
when targeting ligands were attached to liposomes (Zylberberg etal. 2017). Inulin
has been used in the hydrophilic portion of the liposome lamellar architecture as
well as in the outer layer of liposome approach. For example, inulin has been uti-
lized to coat liposomes and stabilize therapeutic ingredients that are labile in lipo-
somes as lipoplexes and polysomes (Xue etal. 2022).
Inulin changed the liposome as a result of the hydrogen bond formation. This
was more important in keeping the liposome in its stable condition. The liposomes
that were treated with inulin continued to have high storage stability. Following
pasteurization, inulin-modied liposomes exhibited improved thermal stability and
antioxidant properties. We show where inulin is found in lipid bilayers and how it
relates to the structure of liposomes. Analysis of the Raman and Fourier-transform
infrared spectroscopy (FTIR) spectra revealed that inulin’s ability to modify the
structural stiffness of liposome membranes is concentration-dependent. The
P. Sharma et al.
61
stability of liposomes was directly correlated with inulin concentrations. The most
notable improvement in liposome stability was observed upon the addition of 1.5%
inulin. On the other hand, the extra inulin decreased the system’s stability, increased
the permeability of the membrane, and decreased the bilayer membrane’s ability to
load cinnamaldehyde. Thus, when the quantity of inulin rose, the stability of lipo-
somes initially increased and subsequently reduced. The outcomes demonstrated
that inulin is a great option for food liposome alteration and stability (Xue
etal. 2022).
3.3.4 Inulin-Based Prodrugs
Another tactic for enhancing the therapeutic use of medications is the creation of
polymeric prodrugs (Rautio etal. 2008). Drugs that are conjugated to polymers
have improved low solubility, poor bioavailability, short plasma half-lives, and
chemical reactivity (Peterson and McKenna 2009). In addition, it diminishes medi-
cation resistance, lowers systemically metabolic, and covers the unpleasant taste.
Drugs with poor blood-brain barrier penetration (Placzek etal. 2016) and limited
selectivity at their point of action might benet from pharmacokinetic and pharma-
codynamic features that can be enhanced with a product (Giang et al. 2014).
Through the use of inulin prodrugs, sustained-release compositions may be designed
with improved cellular drug absorption through pinocytosis; increased plasma half-
life; medication targeting to a particular organ, such as colon targeting (Hartzell
et al. 2013); and decreased toxicity. Since inulin is nontoxic, blood-compatible,
biodegradable, and has therapeutic value, it is a desirable drug carrier when employ-
ing the prodrug method. Two ways are currently being used to produce the inulin
prodrug: stimulating the carboxylic acid via N-Hydroxysuccinimide (NHS)/
1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and modifying the
hydroxyl group of inulin and then attacking it with a nucleophile.
According to Vermeersun etal. (1985), the metronidazole inulin prodrug was
created by succinylating the drug to create metronidazole monosuccinate ester,
which was then coupled to inulin utilizing the 1,10-carbonyldiimidazole (CDI)
chemistry. Combining 5-ASA and inulin, Hartzell etal. (2013) created an ester-
linked combination to create 5-fASA-inulin, a possible prodrug enabling colon-
specic transport of both 5-ASA and inulin into the guts. The amount of gut ora
increased signicantly as a result of the prodrug’s release of 5-fASA.
To increase procainamide’s half-life and guarantee a gradual release, Schacht
etal. (1984) used the prodrug inulin. Procainamide and inulin were linked in this
study to limit drug diffusion throughout the body and to promote cellular absorption
by pinocytosis. In order to conjugate, the hydroxyl group of inulin is rst oxidized
with sodium periodate to produce dialdehyde. Next, procainamide is coupled by
forming the Schiff base and reducing it with sodium cyanoborohydride.
3 Inulin: AVersatile Polymer forDrug Delivery System
62
3.3.5 Inulin-Based Chelating Agents
The construction of a novel inulin compound, aminopropyl inulin (API), connected
to the DO3A ligand (1,4,7,10-tetraazacyclododecan-1,4,7-triacetic acid) via diethyl
squarate was reported by Corsi etal. (2001) (Sharma et al. 2023b). Lebdusková
etal. (2004) created a new inulin compound and a Gd (III) chelate by covalently
connecting inulin to a carboxylic-phosphorus acid derivative of diethylenetriamine
in order to lengthen the rotating correlation time. Pitarresi and colleagues’ results
(2008) showed that iron-rich foods and altered inulin compounds might be used as
a dietary delivery system for iron. Iron was administered orally using the complex
produced combining iron, carboxylated, and thiolated inulin derivative (INU-SA
and INU-SA-Cys). According to the researchers, the derivative showed strong
mucoadhesion capabilities and a great iron-releasing pattern from the copolymer
system of delivery in a situation that mimicked the digestive tract (Pitarresi etal.
2008). Notwithstanding alteration, inulinase still broke down the altered inulin in
along with its release.
3.3.6 Inulin-Based Microparticles
Drugs, vaccine antigens, proteins, and other substances have all been delivered by
inulin microparticles by adsorption, attachment, or entrapment. Inulin microparti-
cles may be made chemically or physically, based on the required physiochemical
characteristics. The procedure to be employed depends on the required particle size
and the drug’s/active ingredients’ chemical characteristics. When utilized as mic-
roparticles, inulin’s biodegradability is crucial since when the particle breaks down,
the drug cargo held in its matrix is freed.
Anjuomo and colleagues (Anjuomo etal. 2019b; Wang etal. 2019) utilized
conjugation chemistry to modify delta inulin particles, which effectively supplied
two distinct antitubercular medications—pyrazinoic acid and isoniazid—to macro-
phages. It was demonstrated that intracellular transport of the produced inulin com-
bines to the tubercle bacilli reservoir could be accomplished. The enhanced
absorption and tropism to monocytes and dendritic cells are attributed to the altered
inulin microparticle, which has a diameter of around 1–2 μm according to the
SEM data.
3.3.7 Inulin-Based Nanoparticles
By attaching to certain receptors with ligands on their surface, nanoparticle can
actively target cancer cells through leaky endothelium or passively through other
means (Hirsjarvi etal. 2011). The dimension of the particles affects how they com-
municate with cells, how they are trafcked, and how much of them are internal-
ized. This corresponds to the system’s effectiveness in delivering.
P. Sharma et al.
63
Nanoparticles of inulin-ibuprofen coupled with Arginine (R), Glycine (G),
and Aspartic acid (D) peptide were created by Zhang etal. (2016) to distribute
epirubicin in an intelligent manner. Enhanced active targeting of the inulin-based
nano-carrier in its delivery of epirubicin was made possible by the altered inulin-
ibuprofen conjugate’s ability to go through self-assembly into nanoparticles,
with ibuprofen creating the hydrophobic core and inulin creating the hydrophilic
shell. Applying a homing ligand, such as RGD peptide, to the outermost layer of
the nanoparticles reduces the possibility of early drug release away from the
target region.
To increase the availability of these avonoids in the human body, a unique
hybrid inulin-soy protein nanoparticle formulation was concurrently loaded with
(-)-epicatechin and quercetin (NEQs), which were produced by spray drying. Cell
viability tests, invitro release, and invitro gastrointestinal digestion were among
the physicochemical and functional characteristics of NEQs that were assessed fol-
lowing process improvement. The ndings support the development of inulin-soy
protein nanoparticles for increased bioavailability of certain advantageously charac-
terized bioactive substances (Jiménez-Sánchez etal. 2019).
3.4 Studies Done onInulin or Products Using Inulin:
Toxicological andClinical Outcomes
Data from clinical studies with inulin-containing medication formulations are few.
Nonetheless, a number of studies on the application of inulin microparticles—more
especially, Advax—as a vaccine adjuvant in various vaccinations show that delta
inulin was effective and well-tolerated (Petrovsky and Cooper 2015). The safety
prole does not raise any concerns or cause a hazardous response. It was determined
that the use of these inulin microparticles in human vaccination trials was safe.
Because of its superior safety prole, it is a viable option as a vaccination adjuvant.
Recently, SARS-CoV-2 vaccine (covid vaccine), which is presently advancing into
human clinical trials, was adjuvant with inulin microparticles.
It is a useful adjuvant and drug delivery vehicle in cancer therapy because of its
unique structure, stability, and nutritional qualities. Focusing on the many roles of
inulin in cancer therapy—such as a synergist, signaling molecule, immunomodula-
tor, and anticancer agent—current efforts aim to develop inulin-based nanomateri-
als and nanocomposites to address several unresolved clinical challenges. Several
unresolved clinical issues are addressed. The study also offers a succinct synopsis
of current observational research and clinical trials related to inulin-based treat-
ment. Conclusively, this study provides valuable perspectives on the noteworthy
function of inulin interventions in investigating the possibility of it as a therapeutic
agent for the treatment of cancer (Ghali etal. 2024).
3 Inulin: AVersatile Polymer forDrug Delivery System
64
3.5 Inulin’s Uses inthePharmaceutical Sector
3.5.1 Colon-Targeting Function ofInulin
Colon illnesses are hard to treat as intravenously injected pharmaceuticals are
removed from the body before they enter the colon, and oral treatments are taken in
at the stomach level. The creation of colon-targeted medicinal compounds thus
becomes crucial for the management of colon illness. The naturally occurring poly-
saccharide inulin is degraded by bidobacteria-produced inulinase, rather than by
the enzymes found in the gastrointestinal tract. The data provided above designates
inulin and its related compounds as biodegradable colon-targeted vehicles for deliv-
ery. A variety of dextran and inulin hydrogels were created to serve as potential
routes of administration for medications into the colon. Drugs enclosed in vesicles
covered with inulin may be discharged straight into the colon because inulin is not
ingested by the stomach and is broken down by colonic bacteria. Consequently, the
usage of vesicles coated with inulin has improved the management of colonic disor-
ders. The colon’s special drug delivery system needs to be ready to safeguard the
medication as it travels there (Ghali etal. 2024). Inulin is neither absorbed nor
digested in the digestive tract, which makes it a desirable delivery system for colonic
medications. With inulin and its related compounds, a number of drug delivery sys-
tems, including tablets, microparticles, microspheres, micelles, nanoparticles,
nanomicelles, and hydrogels, were developed and showed promising outcomes.
Table 3.1 displays some of the dose forms and medication delivery methods for
colon targeting with inulin assistance.
3.5.2 To Maximize Medication Efficacy forTumor Targeting
Inulin has been widely exploited as a linear organic polysaccharide in the produc-
tion of tumor-targeting medication delivery systems because of its exceptional bio-
degradability, biocompatibility, and exibility for straightforward chemical
engineering (Varan etal. 2019). When placed in nano-micelles of lauryl carbamate
analogues of inulin, paclitaxel (PTX) and doxorubicin (DOX) were shown to be up
to 100–200 times effective than those medications in their insoluble forms.
Subsequent research indicates that epirubicin incorporated into inulin-ibuprofen
polymer-based nanoparticles has more anticancer activity than epirubicin in its pure
form (Varan et al. 2019). Additionally, the nanoparticles showed less toxicity.
Table3.1 displays the many efcient dose combinations created to use inulin for
treating tumors.
3.5.3 Medication Based onProteins
The discovery of several protein-based pharmaceuticals has resulted in quick
advancements in biopharmaceutical and microbiological technologies. Since they
P. Sharma et al.
65
Table 3.1 Utilizing inulin to deliver medications
Inulin or inulin
derivatives
Model drug Dosage forms Uses
References
Inulin Iniximab Tablet Colon
targeting
Maurer etal. (2016)
Inulin acetate Indomethacin Microparticles Colon
targeting
Shivhare etal. (2018)
Amphiphilic
inulin
Ornidazole Nanoparticles Colon
targeting
Maris etal. (2001)
Methacrylated
inulin
Prednisolone Gels Colon
targeting
Van Den Mooter etal.
(2003)
Methacrylated
inulin
Bovine serum Hydrogels Colon
targeting
Wang etal. (2018)
Lipoic acid
esteried inulin
Tanshinone IIA Micelles Colon
targeting
Wang etal. (2018)
PEGylated
squalene-grafted
inulin
Doxorubicin Nanoparticle Colon
targeting
Maksimenko etal.
(2014)
Inulin Fisetin Inulin
nanoparticles
Improves
solubility
and stability
Charoenwongpaiboon
etal. (2019)
Inulin-D-α-
tocopherol
succinate
Curcumin Self-
assembling
micelles
Improves
solubility
Tripodo etal. (2015)
Inulin Anthocyanins Microcapsules Improves
stability
Hester etal. (2018)
Hydrophobically
modied inulin
Cinnamaldehyde Nanoemulsions Improves
solubility of
nanoparticles
Cui etal. (2020)
Aminated inulin Folic acid
complex
Modied
release
Controlled Cui etal. (2020)
cannot be eliminated in aqueous solutions, spray-drying, freeze-drying, and evapo-
rative drying are the only methods available. This might have a signicant effect on
the action’s efcacy (Mensink etal. 2015c). A protective agent needs to be employed
throughout these drying processes to prevent unfavorable outcomes. Sugars are
known to shield proteins throughout the drying and post-processing stages. However,
there is a paucity of knowledge on the precise procedures. A 1992 study on the sta-
bilizing characteristics of enzymes (Paolini etal. 2006) concluded that inulin did
not have the same potent stabilizing effects as sucrose, dextran, or sorbitol. An
insufcient stabilizing result may result from a higher degree of polymerization and
less group material.
3.5.4 Enhancement ofDrug Release
For solid oral preparations, the drug needs to dissolve in order for it to be absorbed.
As a result, medications with subpar release patterns and disintegration rates have
3 Inulin: AVersatile Polymer forDrug Delivery System