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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5397_Библиотеки_им_академика_М_И_Перельмана
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created. Furthermore, these materials’ biocompatibility lowers the possibility of
toxicity and immunological reactions, which qualies them for a range of therapeutic uses (Sabbagh and Kim 2022).
The creation of tailored delivery systems that can precisely reach and interact
with particular cells or tissues is one of the main goals of drug delivery research.
Conventional systemic medication delivery frequently causes therapeutic substances to diffuse throughout the body, increasing toxicity and producing off-target effects. By delivering therapeutic molecules specically to the desired location
of action, targeted medication delivery aims to overcome these problems.
Improvements in imaging technology, genetics, and molecular biology have made
targeted drug delivery possible (Mohammed etal. 2022). It is now possible to create carriers that can recognise and bind to specic biomarkers linked to diseases
according to research ndings. This focused strategy reduces exposure to healthy
tissues, which lessens side effects, while simultaneously improving drug accumulation at the illness site. Targeted drug delivery has demonstrated special promise
in cancer therapy. Ligands that preferentially bind to receptors overexpressed on
cancer cells can be used to functionalize NPs. By enhancing the specicity of
medication delivery, this active targeting approach raises the concentration of
therapeutic medicines in tumour tissues. Furthermore, the passive accumulation
of NPs inside the tumour microenvironment is facilitated by the enhanced permeability and retention (EPR) effect, which is frequently observed in tumours
because of leaky vasculature (Abdella etal. 2023). A new age in healthcare has
begun with the development of personalised medicine, wherein patient-specic
medicines are designed to meet their individual needs. Personalised medicine
makes it possible to tailor therapeutic approaches for medication delivery in
accordance with a patient’s unique characteristics, disease prole, and genetic
composition (Chilkoti etal. 2002). This strategy could reduce unfavourable reactions and maximise therapeutic results. Since genomics makes it possible to identify genetic differences that may affect drug response, personalised medicine is
essential. Pharmacogenomics is the study regarding how a person’s genetic
makeup inuences how they react to drugs, helping determine the right dosages
and treatment plans. By incorporating pharmacogenomic data into drug delivery
plans, customised methods that consider a patient’s genetic susceptibility to particular diseases and how they react to particular medications can be developed
(Wening and Breitkreutz 2011).
Personalised medicine has contributed to the development of targeted cancer
medicines that utilize the unique molecular features of individual cancers. Anticancer
drugs can be delivered to cancer cells directly by targeted drug delivery systems,
protecting healthy tissues from the harmful effects of chemotherapy. This raises the
therapeutic index and lowers the chance of developing resistance, which is a typical
problem in the treatment of cancer (Mura and Couvreur 2012). With the introduction of gene therapy—a groundbreaking method with the potential to treat and perhaps cure genetic disorders—the eld of drug delivery is quickly changing. To
address or modify the underlying cause of an illness, gene therapy entails the insertion, modication, or deletion of genetic information within a patient’s cells. One of
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the most crucial aspects of gene therapy is getting therapeutic genes into target cells,
and developing DDSs is essential to maximising the benets of this novel strategy.
Looking ahead to biotechnology, the use of cutting-edge technologies has the
potential to change the landscape of drug delivery yet more. With its ability to analyse data, identify patterns, and make decisions, articial intelligence (AI) is nding
more and more uses in the optimisation of medication delivery systems (Mirza and
Karim 2021). Therapeutic outcomes may be improved by intelligent drug delivery
systems that may modify their release proles in response to physiological inputs
occurring in real time. Large-scale datasets can be analysed by machine learning
algorithms to forecast patient reactions, optimise dosage schedules, and customise
treatment plans for optimal effectiveness. The idea of “smart” medication delivery
systems—in which nanocarriers with sensors and actuators may react dynamically
to the body’s microenvironment—is becoming more and more popular. Therapeutic
compounds can be supplied precisely when and where they are needed thanks to
these systems, which can modify their release kinetics in response to changes in
temperature, pH, or the presence of particular biomarkers (Orive etal. 2003). A
synergistic approach to personalised and adaptive medicine, where treatment plans
are continuously improved depending on specic patient reactions, is represented
by the marriage of AI and drug delivery technology. The development of precision
medicine, driven by advancements in genomes and molecular diagnostics, will be
crucial in determining how drugs are delivered in the future. Targeted therapies can
be developed through the identication of certain biomarkers linked to illness susceptibility, progression, and response to treatment. Treatment plans can be tailored
using biomarker-driven medication delivery strategies to each patient’s specic
genetic composition and disease prole. This strategy may improve treatment efcacy while minimising side effects, ushering in a time when there is no longer a
one-size-ts-all approach to medicine. Beyond conventional small-molecule medications, biologics and nucleic acid-based medicines will continue to grow in the
eld of biotechnology drug delivery (Allami and Yousif 2023). Advanced DDSs
will progressively incorporate gene editing technologies, RNA-based therapies, and
monoclonal antibodies. The difculties in delivering big, complicated biomolecules
will be overcome by creative methods, such as specially designed NPs that can
shield and carry these delicate payloads to their destinations. To sum up, medication
delivery in biotechnology is a vibrant, diverse discipline that has made signicant
strides recently. The current environment is dened by the convergence of targeted
therapies, personalised medicine, and nanotechnology, which presents new opportunities for the treatment of various diseases. Though there are still obstacles,
research and technology advancements keep expanding the realm of possibility
(Hamamoto etal. 2020). Future developments in articial intelligence, precision
medicine, and sophisticated medication delivery technologies have the potential to
completely transform the healthcare industry. There is promise for safer, more
effective, and patient-centred therapeutic treatments soon with the development of
intelligent, adaptable DDSs and the achievement of completely individualised medicine. Drug delivery’s path from bench to bedside is evidence of science’s unwavering quest of greatness, with each discovery bringing us one step closer to a time
when illnesses will be treated with never-before-seen accuracy and effectiveness.
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The purpose of medications and pharmacies is to safely and consistently deliver
any drug towards a specic target in the appropriate dosage at the proper time
(Kaida-Yip etal. 2018). These ideal conditions, however, are more hype than reality for many medications. For instance, adequate peptide or protein medication
delivery has not yet been achieved via the oral route, even though it is one of the
recommended drug delivery modalities because of its non-invasive character. This
is caused in part by the stomach’s acidity, the liver’s rst-pass effect (drug loss due
to metabolism processes prior to entering the systemic circulation), and the intestinal wall’s resistance, which either alters, destroys, or reduces absorption of
almost all macromolecules, lowering their bioavailability (Kos et al. 2018).
Because of this, millions of diabetics globally are forced to administer insulin
shots to themselves on a regular basis, which leads to a high rate of treatment noncompliance. Nasal medication delivery and injection are two more often used drug
administration techniques. Polar compounds are poorly absorbed when administered via nasal administration, whereas injection causes discomfort and makes
patients reluctant to utilise it. The application of medication through the skin is one
substitute for these methods. Drugs need to get through the outer membrane,
known as stratum corneum, which provides a barrier against material diffusion.
Additional signicant obstacles are the intracellular distribution of macromolecular medications, the long- term injection of medications into tumours, and the specic delivery of glycoproteins. In addition to affecting traditional medication
administration methods and dosage forms, the absence of appropriate DDSs is
impeding the development of cutting-edge therapeutic approaches including gene
therapy, RNA interference (RNAi), and cell therapy (Burrows and Lambrix 2022).
A virus is employed as a vector in gene therapy to introduce active and corrected
genes into a patient’s cells. However, the vector can create uncontrollable mutations and cancer if it inserts itself into a cell’s DNA.The tragic death of a volunteer
in a gene therapy experiment in 1999 (Liu etal. 2022) and the recent development
of leukaemia in two children opting gene therapy for the severe combined immune
deciency illness (Birla et al. 2022) demonstrate how serious this therapy is.
Likewise, for RNA interference (RNAi) therapies to full their potential, researchers must devise clever mechanisms to safeguard small interfering RNAs (siRNAs)
in bloodstream and direct them towards the appropriate cells. The disadvantages
have incentivised numerous pharmaceutical and biotech start-ups to create DDSs
that can operate both safely and effectively. However, there are still no scientic
guidelines that offer a clear path forward for the development of drug delivery
technology (Tsiftsoglou etal. 2013). Drug delivery in biotechnology is a dynamic
and transformational frontier in the eld of healthcare, revolutionising the way
therapeutic agents are supplied, targeted, and controlled within the human body.
The advancement of drug delivery techniques within the area of biotechnology has
proven critical in improving treatment efcacy and safety while minimising side
effects.
Current DDSs in
Nanocarriers
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7.2 Current Drug Delivery Systems inBiotechnology
DDSs in biotechnology have made considerable advances in recent years, especially in the development of innovative nanocarriers for the effective transportation
and controlled release of the drug molecules. These nanostructured systems, which
include polymeric micelles, hydrogels, dendrimers, and liposomes, were developed
to minimise the drug dose required to produce a given therapeutic effect, reducing
costs and related adverse effects (Lombardo etal. 2019).
The biotechnology landscape of DDSs (Fig.7.1) is characterised by a variety of
sophisticated techniques aiming to improve the therapeutic effects of drugs. These
systems make use of cutting-edge technology to improve the distribution of drugs,
release kinetics, or target selectivity (Orive etal. 2003).
7.2.1 Nanotechnology
Nanotechnology is currently at the cutting edge of research. Polymeric research is
currently playing a prominent role in the evolution of nanotechnology by providing
regulated release of therapeutic drugs in constant doses over long periods of time,
cyclic dosage, and adjustable release of both hydrophobic and hydrophilic drugs.
Various biomaterials can be employed for this purpose, having a wide range of
chemical properties and potential for further modication with NPs (Bhatia 2016).
NPs have been discovered as the most effective careers in the delivery of conventional medicines, vaccines, nucleotides, and recombinant proteins among all current
advanced delivery systems. Nanoparticulate DDSs can increase drug characteristics
such as pharmacokinetic parameters (such as bioavailability, biodistribution, and
Nanotechnology in
Drug Delivery
Liposomes
Nanoparticles
Polymeric
Fig. 7.1 Numerous drug delivery systems in biotechnology
Targeted Drug
Delivery
Antibody-Drug
Conjugates (ADCs)
Peptide-Based
Targeting
Biotechnology
Biologics and Gene
Therapies
Monoclonal
Antibodies
Gene Editing
Tools
Implantable Devices
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drug release characteristics). Nanoparticulate DDSs enable the effective and controlled release of drugs with site-specic drug delivery, targeting cells or tissues
with minimal adverse effects. As a result, the application of nanotechnology in the
eld of pharmaceutical biotechnology helps in the development of drug delivery
strategies to solve the distribution issues of protein-based pharmaceuticals such as
oligonucleotides and recombinant proteins, among others. Paradise etal. (2008)
discuss some nanotechnologies used in biotechnology.
7.2.2 Liposomes
Liposomes are commonly utilised in biotechnology to support drug delivery. To
initiate drug release processes, they have been functionalized using different stimuliresponsive mechanisms such as heat, ultrasound, light, magnetic elds, pH,
enzymes, and redox. Furthermore, liposomes can combine cancer-targeting compounds for both therapy and diagnostic purposes, making them attractive for theranostic applications (Lombardo etal. 2019).
Furthermore, PEGylated liposomes were also exhibited to enhance stability,
blood circulation time, and plasma clearance, making them useful at directing active
therapeutic molecules to specic areas in biological systems mainly in the distressed
tissues or tumours. The addition of ligands like peptides, monoclonal antibodies
(MAbs), growth factors, and aptamers improves the specicity of liposome interactions during drug release. Overall, liposomes serve an important role in biotechnology by acting as adaptable nanocarriers for drug delivery, allowing for the targeted
and regulated release of therapeutic substances with minimal adverse effects (Muthu
and Feng 2013).
Liposomal nanotechnology is widely employed in biotechnology for a variety of
applications (Table7.1), utilising the unique features of liposomes to improve medication delivery, diagnostics, and therapies. Here are some signicant uses of liposomal nanotechnology in biotechnology.
Table 7.1 Various applications of liposomal drug delivery system in biotechnology
Application Description Example Reference
Cancer therapy Chemotherapeutic substances
Infectious diseases Antibiotics or antiviral
Vaccine delivery Encapsulation of the vaccine
encapsulated for targeted
delivery
substances are encapsulated to
allow targeted delivery to
infected areas
antigens for controlled release
and increased stability
Doxil (liposomal
doxorubicin) and
Myocet
AmBisome (liposomal
amphotericin B)
Epaxal (liposomal
virosomal vaccine for
hepatitis A)
Cagel etal.
(2017), Schütz
etal. (2013)
Adler-Moore
and Proftt
(2002)
Bovier (2008)
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Table 7.1 (continued)
Application Description Example Reference
Diagnostics
(imaging agents)
Biological
research
Theranostic Diagnostic and therapeutic
Biotechnological
tools
Cosmeceuticals Liposomes are utilised for
Liposomes encapsulate imaging
chemicals to improve tissue or
cell visualisation
Liposomes can be used to
deliver certain molecules into
cells for study purposes
properties combined in the same
liposomal system
Liposomes can be employed as
biotechnological tools in
various applications like gene
transfection
topical administration of
cosmetic and medicinal
ingredients
Liposomes containing
Gd-DTPA for MRI
(magnetic resonance
imaging)
Liposomes loaded with
uorescent dye can be
used for cellular
research
Doxil with imaging
capabilities
Gene transfection of
endothelial nitric oxide
(NO) synthase using
liposomes
Antioxidants
incorporated in
liposomes in skincare
products
Guenoun etal.
(2012)
Torchilin
(2005)
Al-Jamal and
Kostarelos
(2011)
Iwata etal.
(2001)
Van Tran etal.
(2019)
7.3 Drug Delivery
111
Cancer Therapy—Chemotherapeutic chemicals are encapsulated in liposomes.
Liposomes can aggregate selectively in tumour tissues thanks to the enhanced
permeability and retention (EPR) effect, causing minimal damages to healthy
cells. Myocet and Doxil (liposomal doxorubicin) are two examples (Cagel etal.
2017). Long-circulating liposomes can accumulate in infected locations with
damaged vasculature via the EPR effect and have been employed for drug administration into tumours by passive accumulation on numerous occasions. Longcirculating liposomes exhibit non-saturable, dose-independent, log-linear
kinetics as well as enhanced bioavailability (Torchilin 2011, Allen and
Hansen 1991).
7.3.1 Vaccine Delivery
Liposomes are employed to encapsulate vaccine antigens to improve their longterm stability and immunogenicity. Controlled antigen release improves vaccine
effectiveness (Schwendener 2014).
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7.3.2 Gene Delivery
Liposomes are used in gene therapy applications to transport genetic material (DNA
or RNA). They safeguard the genetic material while also facilitating cellular intake
(Balazs and Godbey 2011).
7.4 Diagnostic Applications
7.4.1 Imaging Agents
Liposomes can incorporate imaging agents (e.g. contrast agents for MRI and uorescent dyes to obtain optical imaging). Used to improve visibility of specic cells
or tissues.
7.4.2 Theranostic
Diagnostic and therapeutic characteristics combined in the same liposomal system.
It allows for simultaneous imaging and delivery of drugs, allowing for more personalised therapy (Shvets etal. 2013).
7.4.3 Biological Research
Cellular Studies—Liposomes are used as carriers in research to introduce molecules
into cells. Used in the investigation of biological processes and interactions
with drugs.
Intracellular Delivery—Liposomes with suitable modications can carry drugs
or biological substances within the cytoplasm of cells. Aids in intracellular targeting
and cellular function regulation (Philippot and Schuber 1994).
7.4.4 Cosmeceuticals
Topical Delivery—Liposomes are employed in the topical administration of cosmetic and pharmaceuticals. Promotes active ingredient penetration into the skin
(Rahimpour and Hamishehkar 2012).
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7.4.5 Nutraceuticals
Nutrient Delivery—Liposomes may incorporate and transport nutrients or bioactive
chemicals. Increases bioavailability and allows for targeted distribution to certain
tissues (Khorasani etal. 2018).
7.4.6 Research andDevelopment
Drug Formulation Studies—Liposomes are used at early stages of the drug development process to evaluate both the feasibility and efcacy of therapeutic
formulations.
Biotechnological Tools—Liposomes are used in various biotechnological applications, including gene transfection using liposomes in research laboratories
(Jesorka and Orwar 2008).
7.5 Challenges andAchievements
Circulation time and Stability—Long-circulating liposome (PEGylated liposome)
formulation advances address challenges of stability and quick clearance.
Targeting Strategies—Continuous development of innovative targeting ligands
and techniques for improved specicity in drug delivery.
Combination Therapies—Liposomal systems are being investigated for use in
combination medicines to produce synergistic effects.
Liposomal nanotechnology in biotechnology is evolving as an outcome of ongoing research aimed at overcoming obstacles and unlocking new possibilities.
Liposomes’ adaptability makes them a valuable tool for adapting DDSs to meet
specic biomedical needs (Shvets etal. 2013).
7.5.1 Nanoparticles
In the discipline of biotechnology, NPs play an important role in DDSs. They provide various advantages such as controlled release, targeted distribution, and
improved therapeutic effects. NPs are particles having nm size, typically between 1
and 100nm. Therapeutic substances can be delivered by NPs made of various types
of materials, such as proteins, lipids, metals, and polymers.
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Types ofNPs
NPs employed in biotechnology vary in composition, size, and application. These
are some of the most popular NPs used in biotechnology.
Lipid-Based NPs
Lipid-based NPs, typically made of lipids or lipid-like substances, are frequently used
in the administration of drugs because of their biocompatibility. Liposomes and SLNs
are few examples of lipid-based NPs. Liposomes are spherical lipid vesicles composed of lipid bilayers that are frequently utilised to encapsulate pharmaceuticals for
targeted delivery like Doxil (liposomal doxorubicin) is a cancer treatment. SLNs are
NPs with a solid lipid core that improves drug stability and controlled release of drugs.
Hydrophobic drugs are delivered through SLN formulations (du Plessis etal. 2014).
Polymeric NPs
Polymeric NPs are biodegradable polymer-based carriers for drug delivery that provide targeted delivery and controlled release. Examples of polymeric NPs are PLGA
NPs for anticancer drug delivery, and Chitosan NPs have been used to transport
genes (Badwaik etal. 2019).
Metal-Based NPs
Metal-based NPs (MNPs) are made up of metallic elements and are used in imaging,
diagnostics, and drug delivery. MNPs have been used in a variety of industries due
to their distinct characteristics. They have many advantages because of their unique
qualities, but they also have disadvantages because of their shape, size, surface area,
composition, and charge. They are particularly used in medical therapy as carriers of
medicines, biomolecules, and genes. MNPs have been employed as carriers and
contrast agents in imaging and active or passive tumour cell targeting. These MNPs
open the door for novel DDSs, site-by-site targeting, and the delivery of genes. Gold
NPs are well known for their distinct optical features and are employed in photothermal therapy and imaging. Iron oxide NPs, like superparamagnetic NPs, are used in
drug delivery and magnetic resonance imaging (MRI) (Sharma etal. 2022).
Dendrimers
Dendrimers are extensively branched macromolecules having a well-dened structure that, because of their controlled size and form, make them excellent for drug
delivery. Examples: Polyamidoamine (PAMAM) dendrimers are widely employed
in anticancer drug delivery and gene delivery applications (Boas etal. 2007).
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Polymeric Micelles
Amphiphilic block copolymers self-assemble to generate polymeric micelles, which
are NPs that improve the stability and solubility of pharmaceuticals. Pluronic
micelles are triblock copolymers made of poly (ethylene oxide)-poly (propylene
oxide)-poly (ethylene oxide) and are used to deliver poorly water-soluble drugs
(Kwon 2003).
Carbon-Based NPs
Carbon-based NPs include graphene, carbon nanotubes, and fullerenes. These
materials have unique characteristics that make them useful in a wide range of
applications. Carbon nanotubes with functionalized surfaces enables targeted drug
delivery (Majeed etal. 2020).
Silica NPs
Silica NPs are silicon dioxide particles that are well known because of their biocompatibility and exibility of surface functionalization. Mesoporous Silica NPs (MSN)
are NPs with arranged mesoporous structures that are useful for drug delivery and
imaging (Rabiee etal. 2021). The versatility of NPs in biotechnology enables a
wide range of applications, including drug delivery, imaging, and diagnostics. These
are just a few examples of the enormous research and development that has gone
into using NPs to improve medical treatments as well as diagnostics in this area of
biotechnology.
Applications inDrug Delivery
NPs are playing an important role in drug delivery, with applications ranging from
targeted therapy to controlled release, increased bioavailability, intracellular drug
delivery, gene therapy, and imaging. NP surface functionalization enables precise
targeting of certain cells or tissues, reducing side effects and enhancing therapeutic
outcomes. NPs regulated and sustained release characteristics improve drug efcacy by reducing dosing frequency. NPs improve bioavailability and absorption by
addressing the solubility issues of poorly water-soluble drugs (Orive etal. 2003).
Challenges andFuture Prospects
The primary problem for NP-based DDSs is ensuring biocompatibility and understanding potential toxicity. Overcoming the translational gap that separates preclinical achievements and clinical applications is an ongoing problem that requires
strategic advances. Future nanomedicine research will focus on personalised
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