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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5542_Библиотеки_им_академика_М_И_Перельмана-1.pdf
What are Macromolecules
27
When it comes to delivering carriers to the lower intestine, they must
maintain their integrity under stomach conditions during the retardation
period. It is vital to examine the following factors in order to enhance carrier
performance.
1. The interactions of pepsin with the main constituents of the
carrier’s matrix at the molecular level and
2. Carrier structure at the supramolecular level.
Carriers, often used in the literature, could be classified into two groups:
1. Carriers made from natural macromolecules and
2. Lipid-based carriers.
Carriers made by natural macromolecules can be divided into a few
groups:
1. Monophase polysaccharide hydrogels
2. Multiphase polysaccharide hydrogels in the form of blends or
multilayer microbeads, and
3. Polysaccharide– protein hydrogels in the form of blends
4. Lipid-based carriers, such as some vegetable oils and liposomes,
and
5. Lipid–protein carriers.
Various polysaccharide ionic hydrogels have been used as the matrix,
including Ca–alginate (Chan, 2011), alginate–cashew gum (de Oliveira et
al., 2014), cashew gum–inulin (de Barros Fernandes et al., 2016), alginate–
xanthan gum (Zhang S. et al., 2014), xanthan gum–pectin (Qiu al., 2015),
alginate–pectin (Wang et al., 2013), and alginate–chitosan (Xu et al., 2007),
have been utilized as the carrier’s matrix primarily for the entrapment of
hydrophilic active compounds, such as some types of polyphenols. Because
of the amphiphilic characteristics of proteins, polysaccharide–protein
hydrogels are appropriate for the trapping of hydrophobic active chemicals
such as EOs and some types of polyphenols. Lupin (Piornos et al., 2017),
soybean lecithin (Torcello-Gomez et al., 2011), gliadin (Qiu et al., 2015),
whey proteins (Zhang et al., 2016), gelatin (Roy et al., 2009), and many
other proteins are commonly combined with alginate, pectin, and xanthan.
Liposomes can be used to encapsulate both hydrophilic and hydrophobic
active ingredients (Akbarzadeh et al., 2013). Because of their resistance to
pepsin action, vegetable oils derived from long-chain triglycerides are a
viable choice for encapsulating EO (Yara-Varon et al., 2017).
Introduction to the Study of Macromolecules
28
1.11.1. Polysaccharide-Based Carriers
Polysaccharides including alginate, chitosan, and maltodextrin are commonly
utilized to encapsulate EOs in the form of physical or chemical hydrogels
(Ravichandran et al., 2014; GomezMascaraque et al., 2015; Pasukamonset
et al., 2016).
Alginate is a generic term for a group of water-soluble, linear
macromolecules with a large molecular mass (between 32,000 and 400,000
g/mol) derived primarily from brown algae species.
The distribution of mannuronic acid and guluronic acid units in alginate
chains of G-G, M-M, and M-G residue blocks [where G is α-L-gluronic
acid, and M is β-D-mannuronic acid, (Milivojevic et al., 2015)], as well as
their ratio (M/G), are mostly determined by the natural source of alginate
(algae type, season, location, etc.) and dictate the physical and chemical
properties.
Chitosan is primarily made up of (1, 4) connected 2-amino-2-deoxy-Dglucan chains. Chitosan chains act similarly to alginate chains in that they
are semiflexible. At pH 7.0, anion-like alginate chains form a gel with cationlike chitosan chains, with varying rheological behavior depending on the
alginate-to-chitosan ratio. Partial hydrolysis is used to remove maltodextrin
from starch.
D-glucose units are linked in chains of varying lengths in this form of
polysaccharide. Under simulated GI circumstances, Ca–alginate has been
proposed to improve bioavailability, thermal stability, and biological activity
of active substances.
However, weak interactions between active chemicals and the hydrogel
matrix may result in undesired EO leakage. Ca–alginate beads could be
coated with chitosan to boost the carriers’ performance. The development
of alginate–chitosan complexes provides extra carrier stability (Popa et al.,
2000; Anbinder et al., 2011).
Devi and Maji (2009) encapsulated neem EO in chitosan–carrageenan
carriers. Neem seed oil, commonly known as margosa oil, is a marketed
product obtained from the fruits of the neem tree. Antimicrobial action
against Candida utilis, Bacillus cereus, and Bacillus subtilis is ensured by
microencapsulating pimento EO in chitosan and k-carrageenan (Dima et al.,
2014).
Gum Arabic was utilized by Dong et al. (2011) to microencapsulate
peppermint essential oil. Encapsulation ensures that peppermint EO (and
What are Macromolecules
29
its primary constituents, primarily menthol and isomenthol) is released for a
long time (Sarkar et al., 2013).
Maltodextrin is a hydrolyzed starch that is commonly used for
microencapsulation of essential oils (EOs) in combination with surface
active biopolymers such as gum Arabic (Fernandes et al., 2008; Bule et al.,
2010; Kausadikar et al., 2015), modified starches (Bule et al., 2010), and
proteins (Hogan et al., 2003;
Bae and Lee, 2008). It is due to the fact that maltodextrin has high
thermal stability and provides oxidation resistance.
This polysaccharide, however, has a low emulsifying capacity. As a result,
it is preferable to combine maltodextrin with surface-active biopolymers in
order to improve bioactive compound volatile retention during the drying
process (Ersus and Yurdagel, 2007; Fang and Bhandari, 2010; Paz et al.,
2010; Mahadivi et al., 2016; Tolun et al., 2016).
To boost the stability of components like 1,8-cineole and α-terpinyl
acetate, a composite consisting of gum Arabic, modified starch, and
maltodextrin was employed for microencapsulation of cardamom EO
(Krishnan et al., 2005). For microencapsulation of cumin oleoresin,
Kanakdande et al. (2007) utilized comparable carriers.
Cumin volatile EO is made up of terpenes such as β-pinene, p-cymene,
and γ-terpinene), aldehydes (cuminaldehyde, 1,3-pmentha, and 3-p-menthen7-al), and terpene alcohol, according to the researchers. The dextrose
equivalent determines the oxygen barrier characteristics of maltodextrin
(DE).
Better DE carriers ensure more intense interactions between active
chemicals and matrix, resulting in higher encapsulation efficienci . These
carriers are less oxygen permeable. (Touré et al., 2011; Simon-Brown et al.,
2016) have effectively used high DE maltodextrin in the encapsulation of
lemon EO, orange peel EO, cardamom EO, and ginger EO to protect them
from oxidation.
Recently, it was discovered that maltodextrin, when used as a carrier
material, can shield polyphenol chemicals from enzyme action in simulated
GI settings (Romano et al., 2017). Antioxidants and phenolic chemicals have
been transported via xanthan gum, an extracellular microbial polysaccharide
(Da Rosa et al., 2013; Rutz et al., 2013).
Xanthan gum, when combined with maltodextrin and chitosan as a
carrier material, has the capacity to establish strong electrostatic contacts
Introduction to the Study of Macromolecules
30
between the amino groups of chitosan (polycation) and the carboxylic
groups of xanthan gum (polyanion).
Researchers have shown that this sort of mix carrier improves the
regulated release rate of the encapsulated substance (Martínez-Ruvalcaba et
al., 2007; Da Rosa et al., 2013). The biopolymer complexes of xanthan gum
and whey proteins were also found to have the emulsifying capacity and a
good influence on the controlled release of water-soluble nutraceuticals in
W/O/W double emulsion delivery systems.
1.11.2. Protein-Based Carriers
Because of their binding hydrophobic contacts and hydrogen bonding
attraction between molecules, proteins as natural food-grade polymers were
employed as carrier materials for microencapsulation of various EOs: (1)
alone and (2) in combination with polysaccharide hydrogel (Zou et al.,
2012; Haratifar and Corredig, 2014; Chuacharoen and Sabliov, 2016).
Self-cross-linking of protein interchain and intrachain is required for the
formation of a protein carrier matrix. In some circumstances, crosslinking can
be produced by heat treatment or changing the pH of a solution (Shpigelman
et al., 2010; Tavares et al., 2014).
Encapsulation of thermosensitive, hydrophobic bioactive substances has
traditionally been done with protein-based carriers such as gelatin, casein,
whey proteins, and soy proteins (Pool et al., 2013; Xue et al., 2014; Jia et
al., 2016).
The binding affinit of polyphenols and EOs to the protein matrix
determines the encapsulation effectiveness of these carriers (Livney,
2010). The ability of bioactive chemicals to be released from protein-based
transporters is affected by pH. At neutral pH, significant swelling of proteinbased transporters could result in unwanted bioactive chemical leakage
(Kimpel and Schmitt, 2015; Liu et al., 2015).
Key breakdown under stomach conditions due to pepsin attack is a
significant disadvantage of this type of carrier (Kumar et al., 2016). Gelatin
was employed by Sutaphanit and Chitprasert (2014) to microencapsulate
basil essential oil. Methyl eugenol (42.58 percent), caryophyllene (26.88
percent), and eugenol are the main constituents (10.66 percent).
When compared to protein-based carriers, a combination of protein–
polysaccharide carriers can improve delivery system mechanical and release
features while also preventing enzymatic degradation of proteins in stomach
What are Macromolecules
31
conditions (Diaz-Bandera et al., 2013; Jia et al., 2016). Furthermore,
globular proteins, as well as whey protein hydrolysates, have been shown
to have antioxidant activity in numerous studies. They can minimize the
unfavorable oxidation of EOs and improve the carriers’ oxidative stability
(Dryakova et al., 2010; Carneiro et al., 2013).
Encapsulating EOs in protein–polysaccharide carriers is a good way
to (1) stabilize these active chemicals and (2) protect them from chemical
destruction (Turasan et al., 2015; Campelo et al., 2017).
Tween 80 was used to stabilize the oregano EO emulsion, which was
then encapsulated in a variety of microcarriers, including milk powder and
whey protein particles, rice starch particles and inulin, and gelatin–sucrose
composite (Beirao da Costa et al., 2012).
The nutritional quality, ease of preparation, and low cost of polysaccharide
carriers are all advantages. Low encapsulation efficie y, loading capacity,
and release efficienc in the small intestine are all disadvantages (de Oliveira
et al., 2014).
The addition of protein clusters increases the thermal and mechanical
stability of the protein as well as the nutritional value. Low encapsulation
efficien , loading capacity, and release efficienc in the small intestine are
other disadvantages of polysaccharide/protein carriers for encapsulation of
EOs (Dajic Stevanovi’c et al., 2018; Voli’c et al., 2018).
1.11.3. Lipid-Based Carriers
Widely used for encapsulation of EOs, Lipid-based carriers made by
vegetable oils have the following advantages in the capacity of a carrier
(Bilia et al., 2014)
1. Good encapsulation efficien ,
2. Stability of active compounds under storage conditions and under
gastric conditions, and
3. Thermal stability (Campos et al., 2014).
The mixture of Triglycerides (major components) and minor components
(5%), such as glycerolipids, such as monoglycerides and diglycerides,
phospholipids, and non-glycerolipids, such as sterols, tocopherols/
tocotrienols, free fatty acids, vitamins, pigments, proteins, phenolic
compounds, water, and so on, make up vegetable oils (YaraVaron et al.,
2017).
Introduction to the Study of Macromolecules
32
Liposomes and solid lipid carriers are two more forms of lipid-based
particles. Hydrophobic, hydrophilic, and amphiphilic compounds can all be
encapsulated using this sort of carrier (Yoshida et al., 2010).
For the manufacture and encapsulation of EOs, thin film hydration,
freeze–thaw, sonication, and reverse-phase evaporation were the most often
utilized procedures. Liposomes have the following drawbacks:
1. Complex and expensive preparation procedures and
2. Reduced stability under storage conditions that could restrict
their applications (Akbarzadeh et al., 2013).
For the delivery of polyphenol-type catechins (EGCG), solid lipid
nanoparticles and nanostructured lipid carriers were utilized as nanocarriers
(Shi et al., 2013). Proteins and lipid carriers can be coupled to improve
chemical and mechanical stability, as well as encapsulation efficien .
Polyphenols have been successfully encapsulated using carriers created
by combining proteins and lipid components (β-lactoglobulin-medium
chain triglyceride) (Pool et al., 2013). When compared to polysaccharide/
protein carriers, lipid carriers have superior encapsulation efficien , loading
capacity, and release efficiency in the small intestine
However, limited mechanical and thermal stabilities, as well as a difficul
manufacturing technique and higher cost when compared to polysaccharide/
protein carriers, are disadvantages.
1.12. CONCLUSION
The chapter discussed the basic concept of macromolecules. It also discussed
synthetic polymers and biological polymers. This chapter discussed the
science behind the macromolecules and the distribution of the molecular
weight. It discussed macromolecular thermodynamics. Towards the end of
the chapter, it explained the natural macromolecules as carriers for essential
oils – from extraction to biomedical applications.
What are Macromolecules
33
REFERENCES
1. Chen, L., Yang, Z., McClements, D., Jin, Z. and Miao, M., 2022.
Biological macromolecules for nutrients delivery. Biological
Macromolecules, [online] pp.455-477. Available at: <https://www.
sciencedirect.com/science/article/pii/B9780323857598000208?via%3
Dihub> [Accessed 14 June 2022].
2. Dajic Stevanovic, Z., Sieniawska, E., Glowniak, K., Obradovic, N.
and Pajic-Lijakovic, I., 2020. Natural Macromolecules as Carriers for
Essential Oils: From Extraction to Biomedical Application. Frontiers
in Bioengineering and Biotechnology, [online] 8. Available at:
<https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330110/pdf/
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3. Feng, X., 2022. PLANT‐DERIVED MACROMOLECULES IN THE
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Polymeric Coatings. Polymer Reviews, [online] pp.1-35. Available at:
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CHAPTER 2
Cisplatin Derivatives as Antiviral Agents
CONTENTS
2.1. Introduction ...................................................................................... 36
2.2. Inhibition .......................................................................................... 38
2.3. Currently Approved Platinum-Containing Drugs ...............................48
2.4. Active form of Cisplatin ....................................................................49
2.5. Structure-Activity Relationships ........................................................52
2.6. Arguments for Cisplatin-Derivative Drugs ......................................... 54
2.7. Arguments for Polymeric Drugs ........................................................ 55
2.8. Polymer Synthesis ............................................................................. 56
2.9. Antiviral Activity ...............................................................................57
2.10. Vanadocene-Containing Polymers ...................................................64
2.11. Anticancer Activity..........................................................................65
2.12. Spermicidal Activity ........................................................................ 66
2.13. Fibers ..............................................................................................66
2.14. Experimental: Synthesis and Physical Characterization ...................67
2.15. Experimental: Biological Characterization ......................................68
2.16. Conclusion ..................................................................................... 69
References ............................................................................................... 70
Introduction to the Study of Macromolecules
36
The attention is once again on the critical need for antiviral drug research
to address both old and developing virus epidemics. The recent attempt to
restart the smallpox vaccination program to combat biological terrorism
has been halted, in part due to the observation of adverse cardiac events
following vaccination and the Centers for Disease.
2.1. INTRODUCTION
Centers for Disease Control has recommended that people at risk for heart
disease be excluded from the vaccination program. Even though the quantity
and intensity of adverse responses to most, if not all, vaccinations do not
appear to be growing, the fraction of the human population vulnerable to
these issues does appear to be increasing.
Increased lifespan, as well as viral and environmental variables,
are creating a population of immunocompromised people for whom
immunizations are ineffective. Diseases that are caused by ancient
adversaries, like influenza, have always had the potential to produce new
pandemics.
Unlike vaccinations, antivirals have the potential to function against
new variations of existing viruses as well as novel viruses such as SARS
and avian flu, as well as interventions in biological terrorism. Furthermore,
a new attitude seems to be evolving wherein vaccination dangers are widely
accepted, with the rotavirus vaccine being the most recent victim.
Polymeric medications may have several benefits over small molecule
pharmaceuticals now in use. Polymeric pharmaceuticals can either operate
as a drug or as a way of releasing the substance over time. Controlled or
extended drug release allows for a lower concentration of the medication
to be present at any one moment in ordinarily sensitive locations like the
kidneys and liver while increasing the quantity of drug staying within the
target site (s).
Tumor-associated vasculatures, for example, are typically permeable
to plasma proteins and other macromolecules. Both leaky vasculatures
and restricted lymphatic drainage, which are characteristic of tumors and
absent in normal tissue, lead to an accumulation of macromolecules such as
polymeric medicines in the interstitial space of a wide range of malignancies.
This one is referred to as the “enhanced permeability and retention
effect,” or EPR. Trapped polymeric medicines can thus act as polymeric
drugs for a longer period of time or in controlled release of the active