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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5533_Библиотеки_им_академика_М_И_Перельмана.pdf
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
(MLVs), and multivesicular liposomes (MVLs). OLVs and MLVs both have
structures resembling onions, but OLVs also have two to five or more concentric
lipid bilayers. Unlike MLVs, MVLs have a structure resembling a honeycomb and
include a single-bilayer lipid membrane enclosing hundreds of non-concentric water
chambers. Small unilamellar vesicles (SUVs, 30–100 nm), large unilamellar vesicles
(LUVs, >100 nm), and giant unilamellar vesicles (GUVs, >1000 nm) are the three
categories into which ULVs can be further subdivided based on particle size.
Because of their prolonged circulation times and capacity to passively target the sick
region, the majority of currently available commercial products—such as Doxil—
are SUVs. Owing to its multiple chambers, the MVL structure may store a
considerable amount of drug-aqueous solution and offer prolonged release due to
the dispersion of drug molecules and the erosion/degradation of liposomes [47].
Different liposome preparation techniques have been created. The ethanol
injection, double emulsion, and thin-film hydration techniques are among the
frequently employed production procedures. The development of the drug solution(s) and drug loading; in the case of passive drug loading, this step is combined
with step 1; the preparation of MLVs or ULVs; the reduction in size, if necessary;
the aseptic processing; the buffer exchange and concentration; the aseptic processing; the lyophilization, if necessary; and the packaging.
The two primary strategies for medication loading are active and passive drug
loading. Drug molecules may interact with lipids in ionic, covalent, non-covalent,
electrostatic, or steric ways that cause the drug to be confined inside the inner
aqueous space or included in the bilayer of liposomes. AmBisome, Arikayce,
Visudyne, DepoDur, DepoCyte, and Expel are examples of commercialized liposomal products that use the passive drug loading strategy. Vyxeos, the first
approved liposome containing daunorubicin and cytarabine in the same vesicle,
employs a combination of active and passive loading (figure 3.4)[48].
When compared to other nanocarriers, liposomes are known for having minimal
intrinsic toxicity; this is mostly because of the natural phospholipids that make up
most of them [49]. The most often employed phospholipids in the creation of
liposomes are sphingomyelins and lecithin, which may be found in soy and eggs [50].
The ability of liposomes to specifically target diseased tissues by functionalizing
them with targeting moieties has been recognized, and they are valued for these
positive qualities. For their vast therapeutic pharmaceutical uses as drug delivery
systems, they provide a plethora of potential.
3.6.2 Polymeric nanoparticles
Macromolecules known as polymers are created by joining monomers to form
straight or branching strands. As long as they have at least two functional groups
where they may interact with another monomer, these monomers can have any
structure. A polymer might be created to have certain qualities by using the right
monomer(s). Due to their excellent synthetic adaptability, polymers may be tailored to
specific needs by researchers. Chemical derivatization might be used to directly
customize polymers for use in biopolymers [51], or from artificial monomers, which
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Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
Figure 3.4. Nanoparticle-based drug delivery systems.
can result in a wide variety of forms and uses. As stabilizing agents, surfactants are
necessary for the creation of polymeric nanoparticles. The majority of commonly used
surfactants consist of an ionic functional group that can be cationic (like sodium
laurate), anionic (like benzalkonium chloride), or non-ionic (like ethoxylated amines)
attached to a hydrocarbon chain (hydrophobic portion) [52]. Low molecular weight
polymers such as block copolymers (e.g., Pluronic P123) can also act as surfactants
[53]. Reduced nanoparticle surface tension and increased affinity for lipidic structures
are two benefits of the stabilizers [54]. When surfactant surface-modified nanoparticle
systems are utilized, studies of pharmacokinetics and biodistribution demonstrate
enhanced retention of the medication in the body and lower toxicity [55].
Due to their increased surface area, polymeric nanoparticles show many different
surface functional groups, making them ideal for targeted drug delivery [56]. In
addition, they are simple to operate and modify. With no chemical reaction, the
medication loading capacity is likewise large and simple. Polymeric nanoparticles have
a lot of benefits, but they also have some drawbacks, such as toxicity from certain
surfactants used during preparation and the complexity of scaling up production.
Pharmaceuticals made of polymers work as inert carriers to deliver therapeutic
molecules to certain locations. Polymers can be organic and synthetic. For instance,
PAMAM dendrimers are biocompatible and may encapsulate different therapeutic
compounds, but their main disadvantage is toxicity [57]. PEGylated PAMAM
dendrimers have been created to address this, lowering cytotoxicity and liver damage
[58]. PEGylation of polymers improves biodistribution and pharmacokinetics, as seen
in PEGylated surfers with HPMA double bonds. Gelatin and albumin, two proteins
with intriguing properties that make them useful building blocks for the production of
nanoparticles, are also very stable and non-antigenic [59].
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Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
Numerous polymers, such as chitosan, alginate, PLGA (poly (lactic-co-glycolic
acid), and PLA (polylactic acid), as well as collagen, are used to make nanoparticles
because they are biocompatible and biodegradable [60]. Each contains special
qualities including controlled release, pH sensitivity, and the capacity to transport
drugs. A non-ionic hydrophilic polyester called PEG (Poly (ethylene glycol)) is used
to stabilize nanoparticles, stop them from aggregating, and lessen immune recognition [61]. Ovomucin, which is obtained from egg whites, is a naturally occurring
polymer with certain biological roles, although some people may experience allergic
responses to it (figure 3.4).
The advantages of PEG and PLGA are combined in PEG-PLGA, a block
copolymer that makes it simple to self-assemble into micelles that can contain and
release pharmaceuticals under regulated conditions [62]. Even for hydrophilic
pharmaceuticals, it is biodegradable and provides good drug encapsulation.
Overall, polymeric nanoparticles show considerable promise for applications in
targeted drug delivery and nanomedicine, but a comprehensive analysis of their
characteristics and possible limitations is necessary before they can be developed and
used.
3.6.3 Metallic nanoparticles
A significant avenue for the creation of novel medical technology is metal nanomaterials. Metal nanoparticles’ long-term safety in medicine is still mostly unknown
[63]. Several biological applications, such as site-specific in vivo imaging, cancer
detection, and cancer therapy, have already made use of these particles, treatment
for neurological diseases, treatment for HIV/AIDS, treatment for eye and respiratory diseases, and cancer therapy [64]. One of the many uses for metal nanoparticles
is drug delivery [65]. Nanomaterial surface modification is essential to maintain
nanoparticle stability and avoid aggregation. Surface modifications of noble metals,
such as thiol groups, amines, and carboxylic acids, are common [66]. To decrease
non-specific protein absorption and increase therapeutic effectiveness, nanoparticle
surfaces are modified using long-chain polymers like PEG [67].
The exceptional physicochemical features of silver nanoparticles (AgNPs) and a
variety of biological activities, such as antibacterial, antiviral, anti-fungal, and
antioxidant capabilities, have made them well known [68]. When AgNPs contact
with bacteria, silver ions are released, delaying membrane penetration and inhibiting
cellular enzymes. Gold nanoparticles (AuNPs) can deliver pharmacological compounds, proteins, and chemotherapeutic drugs into their targets and are efficient
radiosensitizers [69]. AuNPs are adaptable nanocarriers that exhibit beneficial
properties in the biomedical industry, such as surface functionalization [70].
Palladium nanoparticles (PdNPs) have demonstrated antibacterial and cytotoxic
effects as self-therapeutics and have significant mechanical and catalytic properties
[71]. Owing to their expansive surface and capacity to combat cancer, germs, and
free radicals, platinum nanoparticles (PtNPs) are now being studied in a number of
biotechnological and pharmaceutical disciplines [72]. Due to their distinctive
qualities, low toxicity, and potent antibacterial properties, copper nanoparticles
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Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
(CuNPs) have grown in popularity [73]. Other metal nanoparticles, such as those
made of zinc oxide (ZnO), titanium dioxide (TiO
), and metal sulfide nanoparticles,
2
have intriguing possibilities for anti-cancer, anti-diabetic, and anti-inflammatory
drug delivery systems (figure 3.4).
3.6.4 Quantum dots
Researchers have been more interested in quantum dots (QDs) because of their
extraordinary electromagnetic, luminescent, and adaptable surface chemistry, which
allows for real-time monitoring of QDs vehicle transit and drug release at both
systemic and cellular levels. Inorganic nanomaterials known as QDs have large
luminous excitation spectra and narrow symmetrical excitation spectra that suffer
significant Stokes shifts [74]. Typically, QDs are made of a covering substance to
prevent photobleaching and leakage and a metallic core material that may transmit
fluorescence. The core material is chosen to provide the highest quantum yield.
Researchers are interested in the outstanding electromagnetic, luminous, and
controllable surface chemistry of QDs, which allows for real-time monitoring of
QDs vehicle transit and drug release at both systemic and cellular levels. The
inorganic nanomaterials known as QDs possess broad, symmetrical excitation
spectra with weak Stokes shifts and broad, brilliant excitation spectral. Carbon
dots (CDs), a type of commonly used graphene QD, have cemented their position as
nanostructures due to their high cost-effectiveness, good solubility, simple functionalization, pleasant fluorescence emission, appealing chemical composition, simplicity of large-scale synthesis, and photochemical stability. Surface passivation
enhances fluorescence while surface functionalization increases solubility in both
aqueous and non-aqueous fluids [75]. Synthetic fluorescent CDs, according to
reports, emit light in the deep blue (430 nm) to near-infrared (730 nm) ranges
[76]. Due to these characteristics, CDs are well positioned to give unmatched
performance for a variety of applications, including photodynamic treatment,
biosensing, bioimaging, drug administration, and electrocatalysis [75]. Natural
carbon dots (NCDs) are fluorescent, which provides real-time monitoring and
sensing capabilities to enhance medication distribution. NCDs are biocompatible
contrast agents that are both safe and effective for directing the course of drug
release, particularly for medications that are not water-soluble. Sensing and tracking
probe, photoactivated antibacterial agents, antioxidants, and neurodegenerative
agents are the special uses of NCDs in drug administration (figure 3.4).
3.7 Approved nanomedicines
A large portion of the nanomedicines that are now being researched are improved
release mechanisms for active ingredients that are already being utilized to treat
patients. [77]. They are assessed for this sort of strategy if the pharmacokinetic
profile and biodistribution of these active ingredients are altered by the prolonged
release. If the active component is applied to the target tissue and demonstrates
improved cell uptake/absorption and has a lower organism toxicity profile, it can be
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Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
concluded that the nanoformulation is superior to the present formulation in this
situation [78].
Some of the most often researched nanocarriers for drug delivery include
dendrimers, micelles, liposomes, solid lipid nanoparticles, polymeric nanoparticles,
and superparamagnetic iron oxide nanoparticles [79]. Tables 3.4–3.8 include details
on nanotechnology-based products that have already been given FDA clearance.
Notably, these nanomedicines are commonly able to improve the pharmacokinetic
characteristics of the medication in issue while reducing its toxicity. They are often
created for medications with severe toxicity and poor water solubility.
3.8 Application of AI in GI disease
In recent years, the application of AI in therapeutics for GI diseases has witnessed
significant expansion. Advanced diagnostic technologies, such as capsule endoscopy,
have benefited greatly from the incorporation of AI analysis, leading to improved
patient outcomes and more targeted treatment approaches [86]. One area where AI
has demonstrated great potential is in the classification of patients with biliary
strictures and the identification of potential biomarkers in human bile. AI provides
accurate patient categorization through the use of neural network models, assisting
in early identification and intervention [87]. Additionally, the development of
colorectal cancer prevention strategies has benefited greatly from the use of ML
algorithms to medical examination records. Through retrospective and prospective
clinical studies, AI assists in the diagnosis and prognosis prediction of a variety of GI
diseases, including gastroesophageal reflux disease, atrophic corpus gastritis, acute
pancreatitis, acute lower GI bleeding, esophageal cancer, nonvariceal upper GI
bleeding, UC, and IBD [88]. Clinicians may make better judgments and give patients
individualized care by utilizing these AI-powered technologies. AI has also demonstrated impressive promise for assisting in the identification and categorization of
colorectal polyps, which may boost the use of colonoscopy for effective colorectal
cancer therapies. With the use of this technology, which was created utilizing
convolutional neural network (CNN) models, medical personnel may identify and
characterize polyps with more precision [89]. Additionally, AI-guided tissue analysis
has become a useful tool for forecasting outcomes in patients with stage III colon
cancer, ultimately resulting in improved patient treatment with the help of
pathologists. Doctors can develop customized treatment strategies by utilizing AI
to analyze tissue samples and obtain important information on the behavior of the
malignancy. Furthermore, AI utilization has proven effective in classifying Barrett’s
esophagus cancer, providing a more efficient and accurate diagnosis for this
condition. An AI-based clinical decision-support system has been created for celiac
disease, allowing for more accurate and quick diagnoses [90]. The identification of
significant genes linked to the pathogenesis and prognosis of esophageal squamous
cell carcinoma has also been greatly aided by bioinformatics analyses. These
discoveries might aid in the creation of specific molecular treatments for the illness
[91]. For locally advanced rectal adenocarcinoma, AI-driven identification of long
non-coding RNA signatures has offered the ability to predict patient responses to
3-19
Approved
year References
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
1994 [77, 81, 82]
2000 [83]
[77]
2008
2009
2013
2013
SCID 1990 [77, 80]
and improve circulation
time
leukemia
Multiple sclerosis 1996 [77, 81]
weight and clearance
Controlled molecular
L-glutamine, L-tyrosine and
disease
characteristics
L-lysine
Poly (allylamine hydrochloride) improve circulation time Chronic kidney
Rheumatoid arthritis;
Psoriatic Arthritis;
Ankylosing
Prostate cancer 2002 [77, 80]
and controlled drug
release
PEGylated IFN alpha-2a Improve stability Hepatitis C 2001 [77, 81]
PLGH and leuprolide Improve circulation time
PEGylated IFN alpha-2a Improve stability Hepatitis B and C 2002 [77, 80, 81]
Haemophilia B 2017 [77]
Effective control in
Crohn’s disease;
bleeding
Improve stability and
factor IX
circulation time
fragment
Spondylitis
/Glatopa Random copolymer of L-alanine,
/pegaspargase PEGylated L-asparaginase Improve stability Acute lymphoblastic
®
/pegademase bovine PEGylated ADA enzyme Decrease immunogenicity
®
Table 3.4. FDA-approved polymer nanoparticles coupled with pharmaceuticals or biologicals.
Name Loaded drug/biologics Advantage Indication
Adagen
®
Oncaspar
Copaxone
[sevelamer
®
[sevelamer
®
hydrochloride]/
Renagel
Renagel
®
®
carbonate]
Eligard
PegIntron
/pegfilgrastim PEGylated GCSF protein Improve stability Neutropenia 2002 [77, 81]
®
®
Neulasta
Pegasys
/certolizumab pegol PEGylated Certolizumab
®
Rebinyn GlycoPEGylated Coagulation
Cimzia
3-20
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
2007 [77]
with chronic
kidney disease
Osteoarthritis 2017 [77]
PEGylated IFN beta-1a Improve stability Multiple Sclerosis 2014 [77, 80]
/pegloticase PEGylated porcine-like uricase Improve stability Chronic gout 2010 [77, 80]
®
®
Krystexxa
Plegridy
Extended pain relief over
ADYNOVATE PEGylated factor VIII Improve stability Hemophilia 2015 [77]
Zilretta Triamcinolone acetonide with a
12 weeks
PLGA matrix microspheres
Synthetic ESA Improve stability Anemia associated
/Methoxy
®
polyethylene glycol-epoetin
beta
Mircera
Improve stability Acromegaly 2003 [77]
antagonist
/pegvisomant PEGylated HGH receptor
®
Somavert
ADA—Adenosine deaminase, IFN-Interferon, PLGH—poly DL-lactide-coglycolide, GCSF—Glycine cleavage system H, HGH—Human growth hormone, VEGF—
Vascular endothelial growth factor, ESA - Erythropoiesis stimulating agent, SCID—Severe combined immunodeficiency disease.
3-21
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
[77, 80–82,
Approved
year References
1995
Karposi’s sarcoma;
84]
2005
2008
Ovarian cancer;
multiple myeloma
84]
1999 [77]
Karposi’s sarcoma 1995 [80, 82, 84]
Lymphomatous meningitis 1996 [77, 80–82]
Pulmonary surfactant for respiratory
2000 [77, 80, 84]
distress syndrome
Macular degeneration, wet age-related;
myopia; ocular histoplasmosis
Acute lymphoblastic leukemia 2012 [77, 80–82,
84]
84]
Pancreatic cancer 2015 [77, 80, 82,
Table 3.5. FDA-approved liposome formulations coupled with drugs or biologics.
Loaded drug/
biologics Advantage Indication
Name
decrease systematic toxicity
/Caelyx™ Doxorubicin Improve on-site delivery,
®
Doxil
decrease systematic toxicity
Daunorubicin Improve on-site delivery,
Amphotericin B Reduce toxicity Fungal infections 1995 [77, 80, 81]
®
®
Abelcet
DaunoXome
decrease systematic toxicity
Amphotericin B Reduce nephrotoxicity Fungal/protozoal infections 1997 [77, 80, 81,
®
DepoCyt© Cytarabine Improve on-site delivery,
AmBisome
3-22
controlled release
Reduce toxicity and improve
proteins
SP-8 and SP-C
/
®
Poractant
Curosurf
Verteporfin Improve on-site delivery,
®
alpha
Visudyne
photosensitive release
Improve controlled release Analgesia 2004 [77, 80]
Morphine
®
DepoDur
decrease systematic toxicity
sulphate
Vincristine Improve on-site delivery,
®
Marqibo
decrease systematic toxicity
Irinotecan Improve on-site delivery,
®
Onivyde
Improve controlled release AML or AML-MRC 2017 [77]
cytarabine
Vyxeos Daunorubicin and
AML—Acute myeloid leukemia, AML-MRC—Acute myeloid leukemia with myelodysplasia-related changes.
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
Table 3.6. FDA approved micellar nanoparticles coupled with drugs or biologics.
Loaded drug/
Name
Estrasorb™ Estradiol Improve controlled
Table 3.7. FDA approved protein nanoparticles coupled with drugs or biologics.
Name Description Advantage Indication
Ontak
Abraxane
ABI-007
NSCLC—Non small cell lung cancer
biologics Advantage Indication
release
®
Combination of IL-2
and diphtheria
toxin with
engineered protein
®
/
Paclitaxel
nanoparticles
bound with
albumin
Improve stability
Decrease
immunogenicity
and improve
circulation time
Menopausal
therapy
Cutaneous
T-cell
lymphoma
Breast
cancer;
NSCLC;
Pancreatic
cancer
Approved
year References
2003 [77, 80]
Approved
year References
1999 [77]
2005
2012
2013
[77, 80–82,
84]
neoadjuvant chemoradiotherapy. This personalized approach can optimize treatment plans and improve patient outcomes [92]. Additionally, predictive biomarkers
have been found in the entire blood of IBD patients thanks to ML, facilitating the
use of customized treatments. By analyzing vast amounts of patient data, AI aids in
tailoring treatment strategies to individual needs.
3.9 Future perspectives and challenges
In today’s rapidly advancing technological landscape, achieving interoperability
among various technologies is essential due to the immense amount of data available
at the big data level. Nanoscience and nanotechnology offer vast possibilities,
dealing with objects as small as molecules and atoms. However, at such a minute
scale, a wealth of information is contained in collective data, necessitating data
analytics and mining. AI and its subsets, ML and deep learning, play crucial roles in
this endeavor [88]. AI has made significant strides across various industries,
particularly in medicine, and the convergence of AI with nanoscience holds immense
potential for nanomedicine, including fields like cancer cell research, biomedicine,
and nanobiology. Integrating AI with nanotechnology becomes indispensable when
dealing with nanomedicine and nanoscale drug delivery systems.
In order to establish effective therapeutic strategies, AI has been employed in
identifying cancer subtypes, especially concerning cancer cell phenotypes like
3-23
Approved
year References
Nanobiotechnology and Artificial Intelligence in Gastrointestinal Diseases
1957 [77]
chronic kidney
disease
1957 [77, 84]
chronic kidney
disease
1999 [77, 84]
chronic kidney
disease
2000 [77, 84]
chronic kidney
disease
Psychostimulant 2002 [77]
Psychostimulant 2002 [77]
Muscle relaxant 2002 [77]
Antiemetic 2003 [77, 80]
Table 3.8. FDA approved nanocrystals coupled with drugs or biologics.
Iron dextran Increases the dosage Iron deficiency in
®
Name Description Advantage Indication
INFeD
Iron dextran Increases the dosage Iron deficiency in
®
/
®
Dexferrum
DexIron
SPION coated with dextran Supermagnetic effects Imaging agent 1996 [84]
Sodium ferric gluconate Increases the dosage Iron deficiency in
®
/Endorem
®
®
Feridex
Ferrlecit
Iron sucrose Increases the dosage Iron deficiency in
®
Venofer
3-24
Sirolimus Increase bioavailability Immunosuppressant 2000 [77, 80]
Megestrol acetate Reduce dose Anti-anorexic 2001 [77, 80]
SPION coated with silicone Supermagnetic effects Imaging agent 2001 [85]
®
®
Rapamune
Megace ES
GastroMARK™;
Morphine sulphate Increase bioavailability, release and
®
®
umirem
Avinza
drug loading
Methylphenidate HCl Increase bioavailability, and drug
®
Ritalin LA
loading
Tizanidine HCl Increase bioavailability, and drug
®
Zanaflex
loading
Calcium phosphate Allow cell adhesion and growth Bone substitute 2003 [77]
®
®
Vitoss
absorption
Hydroxyapatite Allow cell adhesion and growth Bone substitute 2003 [77]
Aprepitant Increase bioavailability and allow faster
®
OsSatura
Emend