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12
Inulin: AVersatile Polymer inColon Drug
Targeting
NimeetDesai, VaskuriG.S.SainagaJyothi,
DerajramBenival, SagarSalave, andDigneshKhunt
Abstract
Inulin, a multifaceted carbohydrate, holds numerous therapeutic applications.
Researchers have explored its capabilities as a material for encapsulating drugs.
This is due to its degradability by intestinal enzymes and its prociency in deliv-
ering medications gradually and consistently. Compared to other biodegradable
polysaccharides, the polymer’s distinctive and adaptable structure, stabilization/
protective actions, and ability to target the colon make it an exceptional carrier
for drug administration. This chapter specically examines the several categories
of carrier systems that are based on inulin, including hydrogel, microparticles,
solid dispersions, liposomes, complexes or chelates, prodrugs, and nanocarriers.
The degradation and various modications of inulin for the purpose of targeted
drug delivery applications have also been extensively explored. Furthermore,
this chapter also places signicant emphasis on the topic of toxicity.
Keywords
Inulin · Colon targeting · Drug delivery · Formulations · Polymer
N. Desai · D. Benival · S. Salave (*)
National Institute of Pharmaceutical Education and Research (NIPER),
Ahmedabad, Gujarat, India
V. G. S. SainagaJyothi
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center,
Memphis, TN, USA
D. Khunt (*)
Gujarat Technological University, School of Pharmacy, Gandhinagar, Gujarat, India
264
12.1 Introduction
Targeting specic areas within the gastrointestinal tract is a major area of interest in
pharmaceutical research. With its unique physiological characteristics and slower
transit time, the colon becomes an interesting focus for drug delivery. This is espe-
cially true for medications that are intended to treat localized diseases or have sys-
temic effects by being absorbed in the colon (Hua 2020; McCoubrey etal. 2023).
Multiple advantages are provided by drug delivery systems that target the colon,
including improved therapeutic efcacy, less adverse effects, and higher patient
adherence (McCoubrey etal. 2023). Polymers are increasingly being recognized as
an effective method for targeting the colon because of their adaptability and com-
patibility with biological systems. Various research efforts have investigated differ-
ent strategies within this eld (Kapoor etal. 2023).
Advancements in drug delivery targeted at the colon have been signicant, yet
numerous hurdles still exist that must be overcome to improve both the release and
absorption of medications in this area. One major hurdle involves creating delivery
systems capable of efciently traversing the intricate and ever-changing conditions
of the gastrointestinal tract to specically target the colon (Rabeh et al. 2024).
Additionally, the challenge of ensuring targeted drug delivery to the colon while
preventing early release in the upper sections of the gastrointestinal tract continues
to be a major obstacle. Also, the development of colon-targeted therapies is made
more complex by the requirement to guarantee the safety, stability, and biodegrad-
ability of the delivery systems (McCoubrey etal. 2023).
Tackling these challenges calls for creative strategies and materials that can
accomplish accurate and regulated drug delivery to the colon. Natural polysaccha-
rides are gaining popularity due to their effectiveness in developing drug delivery
systems designed specically for targeting the colon (Giri et al. 2021).
Polysaccharides are long chains of monosaccharides, which are sugars (De Anda-
Flores etal. 2021; Salave etal. 2022a). They are readily accessible and affordable
and come in various forms with a diverse array of features. They have a remarkable
ability to undergo chemical and biological modications. Polysaccharides have
numerous advantageous characteristics, including their safety, lack of toxicity,
exceptional stability, biodegradability, and hydrophilicity. Moreover, their impres-
sive gel-forming capability enables them to function as a versatile carrier for precise
drug delivery to the colon (Giri etal. 2021; De Anda-Flores etal. 2021).
Recently, studies have focused on utilizing polysaccharides to develop a unique
dosage form aimed specically at delivering medication to the colon. This is due to
the unique property of polysaccharides to degrade in the colon, making them an
ideal candidate for this purpose (Giri etal. 2021). Several enzymes, like galactosi-
dase, glucosidase, pectinase, dextranase, amylase, xylosidase, and others, are syn-
thesized by the bacteria found in the colon. The enzymes have a vital function in the
degradation of different polysaccharides found in the colon. Various polysaccha-
rides, including pectin, guar gum, chitosan, amylose, cyclodextrin, chondroitin sul-
fate, dextran, and inulin, have been employed in the eld of targeted drug delivery
for the colon (De Anda-Flores etal. 2021).
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265
Inulin, a natural polysaccharide from the fructan family, has garnered signicant
attention as a versatile polymer suited for targeted drug delivery to the colon, reect-
ing a growing interest in various polysaccharides for this purpose (Giri etal. 2021;
Mensink et al. 2015). Inulin is a fascinating compound that can be found in the
extract of Inula helenium, a perennial herb that grows in Europe, Africa, and Asia.
This substance is present in numerous plants globally and is categorized as a type of
fructans, which are naturally occurring nondigestible oligosaccharides. Table12.1
summarizes inulin content in different plants.
In 1992, the USFDA granted approval to inulin as a nutritional supplement for
infants, deeming it both effective and safe (Giri etal. 2021; Mensink etal. 2015).
Fast forward to 2018, its positive impact on the nutrient value of synthesized food
products was reafrmed. Inulin nds its versatile applications in the food industry,
serving as a fat substitute, sweetener, and stabilizer. This substance is plentiful in
the presence of starch and is not broken down by enzymes in the stomach or intes-
tines. Inulin is extensively used in the pharmaceutical and food industry due to its
various applications. It plays a crucial role in maintaining colon microora, enhanc-
ing metabolism, and promoting gastrointestinal health (Giri etal. 2021; Mensink
etal. 2015). It has a variety of distinctive qualities that make it a highly appealing
choice for this particular purpose. With its remarkable biocompatibility, biodegrad-
ability, and unique capability to be broken down by colonic bacteria, this material is
perfect for creating colon-targeted systems. In addition, the physicochemical prop-
erties of the substance can be adjusted to control how drugs are released and improve
targeting in the colon (Giri etal. 2021; Mensink etal. 2015).
This chapter aims to offer a thorough overview of the different aspects of inulin
as a versatile polymer in colon drug targeting. In this discussion, we will explore the
intricate mechanisms involved in the degradation of inulin in the colon environ-
ment. Additionally, we will examine different modications of inulin that have been
made to improve its effectiveness in targeting the colon. Lastly, we will delve into
the various formulations that have been developed using inulin for the purpose of
Table 12.1 List of different plants with inulin content. Reproduced with permission from refer-
ence (Shoaib etal. 2016)
Inulin source
Plant part
Inulin content (g/100g)
Yacon (Smallanthus sonchifolius) Roots 35
Sweet leaf (Stevia rebaudiana) Leaf 18–23
Garlic, Chinese garlic (Allium sativum) Bulb 14–23
Barley (Hordeum vulgare) Grains 18–20
Chicory (Cichorium intybus) Root 11–20
Jerusalem artichoke (Helianthus tuberosus) Tuber 12–19
Asparagus (Asparagus sp.) Roots 15
Agave (Agave sp.) Stem 12–15
Dandelion (Taraxacum ofcinale) Roots 12–15
Dahlia (Dahlia pinata cav.) Tuber 10–12
Suma (Pfalia glomerate) Roots 11.45
Burdock (Arctium sp.) Roots 8.3–9.9
12 Inulin: AVersatile Polymer inColon Drug Targeting
266
targeted drug delivery to the colon. In addition, we will discuss the potential toxicity
of inulin-based formulations and offer insights into the future possibilities of using
inulin for delivering drugs specically to the colon.
12.2 Need forTargeting Colon
Colon drug delivery is considered as one of the crucial areas in the eld of the phar-
maceutical industry owing to its many benets in treating a range of conditions,
such as ulcerative colitis, Crohn’s disease, colorectal cancer, and infections of the
colon (Hua etal. 2015). By targeting drug delivery on the colon, diseases that affect
this particular area can be treated locally, and systemic absorption can be mini-
mized, perhaps reducing unfavorable side effects (Hua 2020).
Using colonic irrigation to provide drugs, peptides, and proteins that are pH-
sensitive is one of the major benets. The colon is an ideal target for drugs that can be
negatively impacted by the high pH conditions in the upper gastrointestinal tract since
it has a distinct pH environment than the stomach and small intestine (Hua 2020). To
further maximize drug delivery and therapeutic efcacy, colon-specic drug delivery
devices can be created to release drugs at a particular location within the colon.
Oral and rectal administrations are two ways to target the colon. Oral administration
is more commonly accepted due to its noninvasiveness, simplicity, and effectiveness,
but rectal administration is less appreciated because of its discomfort and difculties in
targeting specic areas in the intestinal region (McCoubrey etal. 2023). Oral drug
delivery systems are easier to design and manufacture because they do not require
sterile manufacturing conditions and are also more affordable (Salave et al. 2022b,
2023a; Rana etal. 2023a; Patel etal. 2023). Oral drug deliver to the colon does, how-
ever, come with certain difculties. Given that the colon is the furthest segment of the
digestive system, it is challenging to administer the highest possible dosage of drug
without being degraded and/or absorbed in the stomach and small intestine (García
etal. 2022). Proteolytic activity in the stomach and small intestine can denature drugs,
while the extremely low pH conditions in the stomach might hasten the breakdown of
pH-sensitive proteins and drugs (Liu etal. 2017). Additionally, drugs with low solubil-
ity may dissolve poorly in the intestines due to the lower water concentration.
A considerable amount of studies have focused on exploring various polymers
(natural, synthetic, and semi-synthetic) to overcome challenges associated with oral
colon drug delivery. The use of these polymers allows for the development of a wide
range of drug delivery systems for the colon, including both simple matrix tablets
and more advanced osmotic pressure systems (Arévalo-Pérez et al. 2020).
Polysaccharides and their derivatives are frequently used in the creation of matrix
tablet formulations, making them the most prevalent among all the polymers utilized.
Natural polysaccharides are widely recognized for their minimal toxicity and afford-
ability, rendering them ideal contenders for industrial manufacturing. Furthermore, it
is possible to manipulate them in order to obtain semisynthetic polymers by enhanc-
ing and modifying certain physicochemical properties (Benalaya etal. 2024).
The colon, measuring approximately 150cm, serves as the nal section of the
gastrointestinal tract. It is divided into three unique segments: the ascending,
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