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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5919_Библиотеки_им_академика_М_И_Перельмана.pdf
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- •Preface
- •Contents
- •Contributors
- •1. Introduction
- •2. The Initial Phase of Drug Delivery Systems
- •3. Recent Drug Delivery Systems
- •4. Drug Delivery via Carriers
- •5.4 Polymer-Lipid Hybrid Nanoparticles Drug Delivery System
- •5.5 Self-Micro Emulsifying Drug Delivery System
- •5.6 In Situ Gel Drug Delivery System
- •5.8 Targeted Drug Delivery
- •6. Ceramic-Based Drug Delivery System
- •7. Polysaccharide-Based Drug Delivery System
- •8. Closed Loop Insulin Delivery System
- •9. Liposome-Mediated Drug Delivery
- •5. Recent Drug Delivery Systems
- •5.3 Hexagonal Boron Nitride Nanosheet Drug Delivery System
- •10. Dendrimers
- •11. PEGylated Drug Delivery System
- •12. Antibody-Drug Conjugate System
- •13. Mesoporous Silica-Based Drug Delivery
- •14. Transdermal Drug Delivery System
- •15. Hydrogel-Mediated Ocular Drug Delivery
- •16. Challenges with Current Drug Delivery Systems
- •17. Future Direction and Conclusion
- •References
- •1. Introduction
- •2. Pharmacokinetic Principles
- •2.1 Application of the Pharmacokinetic Principle in the Biomedical Fields
- •3. Cell Membrane/Biological Membrane
- •3.1 Passage of Drugs Across Biological Membranes
- •3.1.1 Simple Transport
- •3.1.2 Specialized Transport
- •4. Routes of Drug Administration
- •4.1 Oral (Enteral) Versus Parenteral Administration
- •4.2 Various Routes of Drug Administration
- •5. Absorption
- •5.1 Factors Affecting Absorption of Drugs
- •5.1.1 Physio-chemical Characteristics
- •5.1.2 Dosage Form
- •5.1.3 Concentration and Volume
- •5.1.4 Blood Flow
- •5.1.5 Surface Area
- •5.1.6 Administration Route
- •5.1.7 Disease States
- •5.2 Gastrointestinal Tract
- •5.3 Parenteral Sites
- •5.4 Pulmonary Sites (Alveoli)
- •5.5 Topical Sites
- •6. Distribution
- •6.1 Factors Affecting Distribution of Drugs
- •6.1.1 Physicochemical Properties of the Drug
- •6.1.2 Binding to Plasma and Tissue Proteins
- •6.1.3 Blood Flow and Organ Size
- •6.1.4 Specialized Compartments and Barriers
- •6.1.5 Specialized Transport Systems
- •6.1.6 Disease States
- •6.1.7 Physiological Factors
- •7. Metabolism/Biotransformation
- •7.1 Functions of Metabolism
- •7.2 Sites of Metabolism
- •7.3.1 Microsomal Enzymes
- •7.3.2 Non-microsomal Enzymes
- •7.4 Pathways of Biotransformation
- •8. Excretion
- •8.1 Routes of Excretion
- •8.1.1 Renal Excretion of Drugs
- •8.1.2 Extra-Renal Excretion of Drugs
- •9.1 Minimum Effective Concentration (MEC)
- •9.2 Maximum Safe Concentration (MSC) or Minimum Toxic Concentration (MTC)
- •9.4 Area Under the Curve (AUC)
- •9.5 Peak Effect
- •9.7 Onset of Action
- •9.8 Onset Time
- •9.9 Duration of Action
- •10. Order of Pharmacokinetic Processes
- •10.1 Zero-Order Kinetics
- •10.2 First-Order Kinetics
- •10.3 Mixed-Order Kinetics
- •11. Pharmacokinetic Models
- •11.1 Compartmental Models
- •11.3 Physiological Models
- •12. Determinants of Pharmacokinetics
- •12.1 Absorption
- •12.1.1 Bioavailability
- •12.1.2 Bioequivalence
- •12.1.3 Area Under Curve (AUC)
- •12.2 Distribution
- •12.2.1 Volume of Distribution
- •12.3 Elimination
- •12.3.2 Clearance (Cl) or Body Clearance
- •13. Conclusion
- •References
- •1. Introduction
- •2. Principles of Targeted Drug Delivery
- •3.1 Changes in pH and Salt Development
- •3.7 Dendrimers
- •4.1 Small-Sized Molecule-Based Targeting Strategies
- •4.2 Nucleic Acid Fragment-Based Targeting Strategies
- •4.3 Peptide- and Antibody-Based Targeting Strategies
- •4.4 Cell-Based Targeting Strategies
- •5. Conclusion
- •References
- •3.4 Liposomes
- •3.5 Solid Lipid Nanoparticles
- •3.6 Co-crystal Preparation
- •1. Introduction
- •2. History
- •3.1 Organic Nanoparticles
- •3.2 Inorganic Nanoparticles
- •4. Nanotechnology-Based Drug Delivery Systems
- •4.1 Smart Drug Delivery Systems
- •4.3 Multifunctional Drug Carriers
- •4.4 Organic/Inorganic Composites
- •5. Nanoparticulate Drug Delivery Systems
- •5.1 Liposomes
- •5.2 Microemulsions
- •5.3 Nanoparticles
- •6. Applications
- •6.1 Enhanced Drug Delivery
- •6.2 Overcoming Biological Barriers
- •6.3 Controlled Drug Release
- •6.4 Combination Therapy
- •6.5 Personalized Medicine
- •7. Limitations
- •7.1 Complexity and Cost
- •7.2 Biocompatibility and Toxicity
- •7.3 Stability and Shelf Life
- •7.4 Drug Loading and Release
- •7.5 Biological Barriers and Clearance
- •8. Conclusions
- •References
- •1. Introduction
- •2. Guidelines for Design of Lipid-Based Formulations
- •3. Formulation Strategies
- •3.1 Lipid Nanoparticles
- •3.1.1 Solid Lipid Nanoparticles (SLNs)
- •3.1.2 Nanostructured Lipid Carriers (NLCs)
- •3.2 Liposomes
- •3.2.1 Conventional Liposomes
- •3.2.2 PEGylated Liposomes
- •3.2.3 Multifunctional Liposomes
- •3.3 Microemulsions and Self-micro Emulsifying Drug Delivery Systems (SMEDDS)
- •3.4 Hybrid Systems
- •3.4.1 Lipid-Polymer Hybrid Nanoparticles
- •3.4.2 Lipid-Protein Hybrid Systems
- •4. Advanced Characterization Methods
- •4.1 In Vitro and In Vivo Assessment
- •4.1.1 Dissolution Studies
- •4.1.2 Permeability Studies
- •4.2 Imaging Techniques
- •4.2.1 Electron Microscopy
- •4.2.2 Fluorescence Imaging
- •Fluorescent Probes
- •Confocal Microscopy
- •4.2.3 Magnetic Resonance Imaging (MRI)
- •4.3 Stability Studies
- •4.3.1 Oxidative Stability
- •4.3.2 Thermal Stability
- •5. Applications of Lipid-Based Drug Delivery Systems
- •5.1 Cancer Therapy
- •5.1.1 Targeted Drug Delivery
- •5.1.2 Combination Therapy
- •5.2 Central Nervous System Disorders
- •5.2.2 Neuroprotective Effects
- •5.3 Antiviral and Antimicrobial Applications
- •5.3.1 Lipid Nanoparticles for Antiviral Drugs
- •5.3.2 Antibiotic Delivery Systems
- •6. Future Perspectives and Challenges
- •7. Conclusion
- •References
- •1. Introduction
- •3. Design and Characterization of Polymeric Drug Delivery Systems
- •4. Responsive Polymers
- •4.1 Polymeric Hydrogels
- •4.1.1 Characterization of Polymeric Hydrogels
- •Structural Analysis
- •Functional Analysis
- •4.2 Polymeric Micelles
- •4.2.1 Characterization of Polymeric Micelle
- •Critical Micelle Concentration Determination (CMC)
- •Morphological Characterization
- •Physicochemical Characterization
- •4.3 Liposomes
- •4.3.1 Ethosome
- •4.3.2 Transferosome
- •4.3.3 Niosome
- •4.4 Polyplexes or Polymer-Drug Conjugates
- •4.4.1 Dendrimers
- •4.4.2 Polymer-Protein Conjugates
- •4.4.3 Polymeric Nanoparticles
- •5. Conclusion
- •6. Future Prospects
- •References
- •1. Introduction
- •2.1 Types of Stimuli
- •3. Mechanism of Stimuli Responsiveness
- •3.1 pH-Responsive Systems
- •4. Materials
- •4.1 pH-Responsive Materials
- •4.4 Synthetic Thermo-Responsive Materials
- •4.7 Magnetic Responsive Materials
- •4.8.1 Intrinsically Conducting Polymers
- •4.8.2 Hydrogels
- •5. Methods
- •5.1 pH-Responsive Drug Delivery Systems
- •6. Conclusion
- •7. Notes
- •References
- •1. Introduction
- •3. Basic Features Required for the Biomaterial
- •4. Characteristics of Biomaterials
- •6. Biocompatibility as the Crucial Item
- •7. Biomaterials in Drug Delivery
- •8. Controlled Drug Delivery
- •9. Clinical Need for Controlled Drug Delivery
- •10. Biomaterials for Controlled Release of Small Molecules
- •11. Bioresponsive Polymers: From Design to Implementation
- •11.3 Hydrolysis and Enzymatically Responsive Polymers
- •11.7 Swelling and Contracting Polymers
- •12. Transdermal Drug Delivery Systems
- •12.1 Barriers to Transdermal Delivery
- •12.2 Development of Transdermal Drug Delivery Patches
- •12.3 Hydrogels Versus Non-hydrogel Polymeric Patches
- •12.4 Patches Based on Biopolymers
- •12.5 Patches Based on Synthetic Polymers
- •12.6 Drug Particles/Carriers
- •12.7 Commercial Patches
- •13. Smart Biomaterials
- •14. Conclusion and Future Perspective
- •References
- •1. Introduction
- •1.1 Historical Evolution
- •2. Skin Anatomy and Physiology
- •2.1 Cutaneous Layer Organization
- •2.2 Cutaneous Barrier Function
- •3. Mechanisms of Transdermal Drug Delivery
- •4. Formulation Strategies for Transdermal Drug Delivery
- •4.1 Drug Selection Criteria
- •4.2 Vehicle and Excipient Considerations
- •4.3 Permeation Enhancers
- •4.4 Transdermal Drug Delivery Technologies
- •5. Evaluation Methods for Transdermal Drug Delivery Systems
- •6. Applications of Transdermal Drug Delivery
- •6.1 Therapeutic Areas
- •6.2 Case Studies of Successful Transdermal Products
- •7. Regulatory Considerations and Approval Process
- •7.1 FDA Guidelines for Transdermal Drug Delivery Systems
- •7.2 Quality Control and Manufacturing Standards
- •7.3 Clinical Trial Requirements
- •8. Challenges and Future Perspectives
- •8.1 Overcoming Cutaneous Barrier Properties
- •8.2 Expanding the Range of Deliverable Drugs
- •8.3 Intelligent and Responsive Transdermal Systems
- •8.4 Integration with Other Drug Delivery Technologies
- •8.5 Conclusion
- •References
- •1. Background
- •2. Importance of the Tumor Microenvironment (TME) in Cancer Progression and Therapy
- •2.1 Components of the TME
- •2.2 Therapeutic Targeting of the TME
- •2.3 Impact of Standard Therapies on the TME
- •3. Tumor-Homing Peptides
- •3.1 Different Strategies for Targeting Peptides to Tumor Microenvironment
- •3.2 Applications and Development
- •3.3 Examples and Discoveries
- •4. Tumor Microenvironment Responsive Drug Delivery Systems (DDSS)
- •5. Nanoparticle-Based Smart Drug Delivery Systems
- •5.1.1 Endogenous Stimulus-Responsive Drug Delivery Systems (DDSs)
- •5.1.2 Exogenous Stimulus-Responsive DDSs
- •5.2.2 Dynamic Strategies for Tumor Targeting
- •6. Challenges and Opportunities for Targeted Delivery to Cancer Cells
- •7. Future Directions
- •8. Conclusions
- •References
- •1. Introduction
- •2. Materials
- •2.1 Types of Biosensors
- •2.1.2 Smart Polymers
- •2.1.3 Microfabricated Devices
- •2.2.1 Enzyme-Based Biosensors
- •2.2.2 Antibody-Based Biosensors
- •2.2.3 Aptamer-Based Biosensors
- •2.2.4 Whole-Cell-Based Biosensors
- •3. Methods
- •3.1 Approach Toward Designing Biosensors
- •3.1.1 Selection of the Analyte and Bioreceptors
- •3.1.2 Immobilization of Biosensors
- •3.1.3 Selection of Transducer
- •3.2 Green Biosensors
- •3.3 Challenges in Development of Biosensors-Based Drug Delivery Systems
- •References
- •1. Introduction
- •3. Ocular Barriers Hindering Absorption of Drugs
- •3.1 Precorneal Barriers
- •3.1.1 Tear Film, Tear Turnover, and Nasolacrimal Duct Drainage
- •3.1.3 Conjunctival and Scleral Barriers
- •3.2 Corneal Barrier
- •3.3 Blood-Ocular Barriers
- •4. Various Routes for Ocular Drug Delivery
- •4.1 Topical Administration
- •4.2 Subconjunctival Administration
- •4.3 Transscleral Administration
- •4.4 Intracameral Administration
- •4.5 Intravitreal Injections/Implants (IVIs)
- •4.6 Retrobulbar Administration
- •4.7 Systemic Administration
- •5. Nanotechnology-Based Ocular Drug Delivery Platforms
- •5.1 Nanoparticles (NPs)
- •5.1.1 Polymeric Nanoparticles (PNPs)
- •5.2 Nanomicelles
- •5.3 Nanoemulsions (NEs)
- •5.4 Nanosuspensions
- •5.5 Nanocrystals (NCs)
- •5.6 Liposomes
- •5.7 Microemulsions
- •5.8 Niosomes
- •5.10 Dendrimers
- •5.11 Nanowafers
- •5.12 Cubosomes
- •5.13 Bilosomes
- •5.14 Olaminosomes
- •5.15 Contact Lenses
- •5.16 Hydrogels
- •5.17 Microneedles (MNs)
- •6. Alternative Ocular Drug Delivery Approaches
- •6.1 Gene Therapy
- •6.1.1 Viral Vectors
- •6.1.2 Non-viral Vectors
- •6.1.3 Antisense Oligonucleotides (ASOs), RNAi, CRISPR-Cas9
- •6.2 Exosomes
- •6.3 Self-nano Emulsifying Drug Delivery Structures (SNEDDS)
- •7. Clinical Status of Nanotechnology-Based Ocular Drug Delivery Systems
- •8. Future Outlooks
- •References
- •1. Introduction
- •2. Anatomy and Physiology of GIT
- •2.1 Mouth and Esophagus
- •2.2 Stomach
- •2.3 Small Intestine
- •2.4 Ruminant Digestive System
- •3. Blood Supply
- •4. Nerve Supply
- •5. Challenges in GIT Drug Delivery
- •5.1 Acidic Environment of the Stomach
- •5.2 Alkaline pH of the Intestine
- •5.3 Variable GI Transit Times
- •6. Future Opportunities in GIT Drug Delivery
- •6.1.1 Targeted Delivery Systems
- •6.1.2 Ligand-Conjugated Nanoparticles
- •6.1.3 Liposomes
- •6.1.4 Solid Lipid Nanoparticles
- •6.2 Controlled Release Systems
- •6.2.1 Osmotic Pumps
- •6.2.2 Matrix Systems
- •6.3 Mucoadhesive Systems
- •6.3.1 Mucoadhesive Polymers
- •6.4 Absorption Enhancers
- •6.5 Tight Junction Modulators
- •6.6 Development of Prodrugs
- •7. Conclusion
- •References
- •1. Introduction
- •2. Anatomy and Physiology of the Respiratory System
- •3. Traditional Methods of Respiratory Drug Delivery
- •3.1 Metered-Dose Inhalers (MDIs)
- •3.2 Dry Powder Inhalers (DPIs)
- •3.3 Nebulizers
- •3.5 Improved Patient Compliance Through User-Friendly Devices
- •3.8 Enhanced Absorption by Overcoming Biological Barriers
- •3.9 Macromolecule Delivery Facilitation
- •3.10 Reduced Side Effects Through Improved Targeting
- •3.11 Formulation Challenges Addressed
- •3.12 Smart Technology Integration for Personalized Treatment
- •3.13 Environmental Sustainability Considerations
- •4. Novel Drug Delivery Approaches
- •4.2 Liposomal Formulations
- •5. Advanced Inhalation Devices
- •6. Targeted Drug Delivery Strategies
- •6.2 pH-Responsive Drug Release
- •7. Emerging Therapeutics for Respiratory Diseases
- •8.2 Combination Therapies
- •8.3 Prodrug Approaches
- •9. Personalized Medicine in Respiratory Drug Delivery
- •10. Future Perspectives and Emerging Technologies
- •10.1 3D-Printed Inhalers
- •11. Conclusion
- •References
- •1. Introduction
- •2. Delivery of Small Molecules
- •3. Drawbacks of Conventional Drug Delivery System
- •4. Factors Affecting Cardiovascular Drug Targeting System
- •4.1 Particle Shape
- •4.2 Particle Size
- •4.3 Particle Density
- •4.4 Flow Characteristics
- •5. Various Targeted Drug Delivery Systems
- •5.1 Application of Exosomes and EVs (Extracellular Vesicles)
- •5.4 Nanomedicines in Cardiovascular Therapy
- •5.5 PLGA-Based Nanoparticles
- •5.6 Liposomal Delivery Systems
- •5.7 Delivery of Biologicals
- •5.8 RNA-Based Delivery
- •5.9 Therapeutic Proteins and Peptides
- •6. Future Perspectives and Challenges
- •7. Conclusion
- •References
- •1. Introduction
- •2. Materials
- •2.1 Equipment
- •2.2 Drugs
- •3. Methods
- •3.1.1 Extrusion-Based 3D Bioprinting
- •3.1.2 Inkjet 3D Bioprinting
- •3.1.3 Light-Based Bioprinting
- •3.1.4 Laser-Assisted Printing
- •3.2 Multiple Drug Delivery
- •3.2.1 Multilayer Films with Capsule-Integrated Polypeptide/Polyelectrolyte
- •3.2.2 Multilayer Shells Using Polypeptides/Polyelectrolytes (PL or PG) and LbL Assembly
- •3.3.1 Physical Stimulation-Responsive Drug Delivery Systems
- •3.3.4 Light-Responsive Drug Delivery Systems (LRDDS)
- •3.4 Small Molecule Delivery System
- •3.4.1 Intraarticular Delivery System
- •3.5 Gene Delivery System
- •3.6 Stem Cell Technology
- •4. Conclusion
- •References
- •1. Introduction
- •2. Importance of Targeted Drug Delivery to the Reproductive System
- •3. Challenges in Drug Delivery to the Reproductive System
- •4. Advances in Drug Delivery Systems
- •4.2 Liposomes
- •4.3 Hydrogels and Biodegradable Polymers
- •4.4 Injectable and Implantable Devices
- •4.5 Micro- and Nano-Needles
- •4.6 Spermbots
- •5.1 Vaginal and Cervical Delivery
- •5.2 Uterine and Intrauterine Delivery
- •5.3 Penile and Testicular Delivery
- •6. Targeted and Precision Medicine Approaches
- •6.1 Hormone Replacement Therapy (HRT)
- •6.2 Gene Therapy and RNA-Based Approaches
- •6.3 Personalized Medicine in Reproductive Disorders
- •7. Therapeutic Applications and Innovations
- •7.1 Infertility and Assisted Reproductive Technologies (ART)
- •7.2 Treatment of Reproductive Cancers
- •7.4 Contraceptive Technologies
- •8. Safety and Regulatory Considerations
- •9. Future Directions and Emerging Trends
- •References
- •1. Introduction
- •2. Liposomes
- •3. Preparation of Liposomes
- •3.1 Reagents
- •3.2 Hydration and Liposome Extrusion
- •3.4 Conjugation
- •3.8 PEGylation
- •3.8.1 Materials Required
- •3.8.2 Procedure
- •3.9 Liposomal Doxorubicin (LD)
- •3.10 Marqibo (Vincristine Sulfate)
- •3.11 DepoCyt (Cytarabine)
- •4. Poly(Lactic-co-Glycolic Acid, PLGA) Nanoparticles
- •4.2 Methods
- •4.2.1 Reagents
- •4.2.2 Procedure
- •5. Polycaprolactone (PCL)
- •5.2 pH Sensitivity and Stability
- •5.3 Methods
- •5.3.1 Materials
- •5.4 Drug Loading
- •6. Chitosan-Based Systems
- •6.1 Encapsulation of Nucleic Acids and Proteins
- •6.3 pH Sensitivity and Stability of Chitosan Nanoparticles
- •6.4 Methodology
- •6.4.1 Reagents
- •6.4.2 Procedure
- •7. Dendrimers
- •7.1 Antisense Oligonucleotides
- •7.2 Small-Interfering RNA (siRNA)
- •7.4.1 Divergent Method
- •7.4.2 Convergent Method
- •8. Challenges in Developing Orphan Drugs
- •References
- •1. Introduction
- •2. Vaccine Delivery Systems
- •3. Polymers
- •4. Non-biodegradable NPs
- •5. Calcium Phosphate NPs
- •6. Colloidally Stable Nanoparticles
- •7. Proteasomes
- •8. Liposomes
- •9. Virus-like Particles (VLPs) and Virosomes
- •10. Immune-Stimulating Complexes ISCOMs
- •11. Emulsion Delivery Systems
- •12. Exosome-Based Vaccine Delivery System
- •13. Immunotherapy Using Nano- and Microparticles
- •14. Properties and Role of Nanoparticles in Drug Delivery
- •15. Biomimicry
- •16. Micellar Systems
- •17. Hydrogels
- •18. Edible Vaccines
- •19. Plant-Derived Viruses
- •20. Melt-in Mouth Strips
- •21. Transdermal Delivery
- •22. Delivery of Nucleic Acids
- •23. mRNA Delivery
- •24. Delivery of Cytokines
- •25. DC Targeting
- •26. Drug Delivery Targeting T Cells
- •27. Conclusions
- •References
- •1. Introduction
- •2. Materials
- •2.1 Equipment
- •2.2 Reagents and Solutions
- •3. Methods
- •3.1 Adenovirus
- •3.3 Retroviral Vectors (RV)
- •3.4 Lentivirus (LV)
- •4. Conclusion
- •References
- •1. Introduction
- •2. Technologies Utilizing Cells in Treating Diseases
- •2.1 Somatic Cell Technologies
- •2.2 Immortalized Cell Lines
- •2.5 Genome Editing Technologies
- •2.6 Cell Plasticity Technologies
- •3. Different Kinds of Cells Are Utilized in the Process of Cell Treatment
- •4. The Practices of Regenerative Medicine and Cell Therapy
- •4.1 Veterinary Medicine Therapeutic Uses
- •5. Advancements and Challenges in Drug Delivery
- •6. Drug Delivery Systems and Applications
- •6.2 Drug Nanocarriers Based on Hyaluronic Acid
- •6.3 Hexagonal Boron Nitride Nanosheet Drug Delivery System
- •6.4 Polymer-Lipid Hybrid Nanoparticles
- •6.6 In Situ Gel Drug Delivery System

Biosensor-Based Drug Delivery Systems: Innovations, Applications, and… 229
bio-recognition element of the sensor identifies the target analyte,
while a transducer converts the result of the molecular recognition
into an electrical signal. Different biomolecules such as enzymes,
nucleic acids, antibodies, proteins, and peptides can be used as a
bio-recognition element and biosensors can thus be used to detect
specific physiochemical changes in the body (associated with the
diseases) with high sensitivity and specificity. The performance of
the biosensors can be optimized on the basis of selectivity, sensitivity, linearity, response time, reproducibility and stability.
Biosensors can be integrated into drug delivery devices to
provide feedback on drug levels and trigger drug release when
needed. These systems can maintain therapeutic drug concentrations and avoid under- or over-dosing. For instance, biosensorcontrolled insulin pumps can measure glucose levels and release
insulin accordingly in diabetic patients [
1].
It is important to mention here that an in-depth knowledge of
the physiology, pathophysiology of the disease, and pharmacodynamics and pharmacokinetics are sine qua non for development of
biosensor-based drug formulations.
2.1 Types of Biosensors
Different types of biosensors featuring drug delivery systems have
been developed with the ability to deliver drugs in response to
biosensor readings. It is important here to know about the fundamental structuring and classification of a biosensor based on its
components and functioning.
The bioreceptors are considered as the primary component in
biosensor construction. Based on the bioreceptor, biosensors are
classified as enzymatic biosensors (most common biosensor class),
immunosensors (possess high specificity and sensitivity and are
specifically useful in diagnosis), aptamer or nucleic acid-based biosensors (possess high specificity for microbial strains and nucleic
acid-containing analyte), and microbial or whole-cell biosensors.
The second classification is made on the basis of the transducer
and sensors which are categorized as electrochemical (which is
further grouped as potentiometric, amperometric, impedance,
and conductometric), electronic biosensor, thermal biosensor,
optical, and mass-based or gravimetric.
Some classifications are made depending on the detection system (optical, electrical, electronic, thermal, mechanical, and magnetic) and rest on the technology (nano, surface plasmon resonance
(SPR), biosensors-on-chip (lab-on-chip), electrometers, and
deployable).
Several types of biosensors have been described here.
2.1.1 Bio-Micro-ElectroMechanical Systems (BioMEMS)
The development of Micro-Electro-Mechanical Systems (MEMS)
devices involves a micro-fabrication process utilizing materials such
as silicon, glass, and plastic. The process begins with patterning
techniques, where photolithography creates desired patterns on the

230 Disha Pant et al.
wafer surface. The wafer is coated with photoresist and exposed to
radiation through a mask, transferring the pattern before the photoresist is removed [2].
Next, a deposition process applies thin films of various materials, such as bioelectronics, polymers like polydimethylsiloxane
(PDMS) and polymethylmethacrylate (PMMA), silicon dioxide,
silicon nitride, metals for electrodes, or biomolecules, onto the
wafer surface. This is followed by etching, which can be either
wet (using liquid chemicals) or dry (involving gas-phase chemistry). Wet etching can be isotropic, etching equally in all directions
and causing mask undercutting with a rounded etch profile, or
anisotropic, which is directional etching induced by chemical or
physical means.
The final step is bonding, where two substrates are joined
together through anodic or fusion bonding techniques [
2].
BioMEMS technology has advanced the fabrication of both
disposable and implantable drug delivery systems and diagnostic
tools. MEMS technology has enabled the creation of microfluidic
devices, designed for sensing, pumping, mixing, monitoring, and
controlling small fluid volumes. Microneedles, including solid,
durable, solid degradable, and hollow types, are used for insulin
delivery (e.g., Jewel Pump by Debiotech) and vaccination (e.g.,
Intaza by Sanofi Pasteur) [
3]. Implantable drug delivery microde-
vices developed with BioMEMS technology aim to address challenges associated with conventional implantable devices, such as
unintended drug release (Fig.
2).
Implantable MEMS drug delivery devices contain reservoirs
loaded with drugs, which are crucial components. The reservoir
materials must be biocompatible externally and inert internally to
prevent drug interactions. Common materials include PDMS,
polyacrylamide, medical-grade silicone rubber, and Pyrex© due to
their desirable properties like biocompatibility, bonding, and optical transparency. Advances in microfabrication have enabled the
creation of appropriately sized reservoirs that balance drug load
Fig. 2 Biosensors and drug delivery systems

Biosensor-Based Drug Delivery Systems: Innovations, Applications, and… 231
capacity and effective drug release mechanisms without significantly
increasing device size. Miniaturization is essential for initial animal
testing and eventual human application, ensuring precise and controllable drug delivery.
Micropumps are crucial components in microfluidic drug delivery devices, enabling precise control over drug dosage and release
rate in targeted tissues. They can be programmed to administer
drugs consistently, preventing fluctuations in drug levels in the
bloodstream. Key parameters for micropumps include size, low
heat generation, precise metering, low power consumption, and
system integration. Micropumps are classified into mechanical
(e.g., piezoelectric, magnetic) and non-mechanical (e.g., electrochemical) types, both of which can be miniaturized for implantation. The need for an external power source and the energy
required for operation are critical factors affecting the feasibility of
implantation.
Through BioMEMS technology, a piezoelectric pumpcontrolled drug delivery system has been developed for transdermal
insulin delivery via microneedles, improving precision and accuracy
compared to mechanically controlled pumps [
4]. To enhance lon-
gevity and biocompatibility, future BioMEMS devices may utilize
biodegradable polymers or compounds that mitigate tissue
responses, such as antibiotics or anti-inflammatory agents
[
5]. Some of the preparations are listed in Table 1.
Table 1
Single reservoir-based MEMS devices for drug delivery applications
Working
S.
Drugs loaded
no.
1. Aqueous
solutions
2. Adrenaline Electrochemical PDMS, polyolefin,
3. Methylene blue
Docetaxel
4. Sodium salicylate Phase change Parylene-C
5. Doxorubicin
hydrochloride
PDMS, polydimethylsiloxane
mechanism of
MEMS
Piezoelectrical Silicon water, silver
Magnetic PDMS,
Electrochemical PDMS
Materials used Dimensions Reference
PDMS
platinum/
titanium
iron oxide particles
PDMS
Microtubing
Paraffin wax
wafers
Silicon
Titanium gold
(8 × 8) mm 100 micron [6]
10 mm × 10 mm × 2mm [7]
5 mm × 3 mm × 12 mm
2 mm × 1 m m× 12 mm
8mm × 8mm × 3mm [9]
mm × 13 mm × 3.5 mm
13
[8]
[10]

232 Disha Pant et al.
While designing the size of the pumping device of MEMSbased delivery systems, its energy consumption, shelf life, and
inability to interfere with physiology and feasibility of implantation
have to be kept in mind. Among the available options, mechanical
pumps like piezoelectric, magnetic and non- mechanical pumps like
electrochemical induced forces based pumps are preferred.
Mechanical micropumps conceptualize oscillating diaphragms
for moving fluids across pressure gradient. They push and halt fluid
and develop a pulsating flow due to their periodicity. Their general
construction includes a flexible membrane or diaphragm, an actuator, a pumping chamber, an inlet, and an outlet.
Mechanical micropumps, also known as displacement micropumps, utilize the movement of components like oscillating diaphragms to pump fluids by applying pressure. These pumps
generate a pulsating flow due to their periodic operation and consist of key components such as a flexible membrane or diaphragm,
an actuator, a pumping chamber, an inlet, and an outlet. The
oscillatory movement of the membrane, driven by a physical actuator, creates the pressure difference needed for fluid pumping.
Common driving forces in mechanical micropumps for MEMS
drug delivery devices include piezoelectric, magnetic, and material
phase change mechanisms.
Non-mechanical micropumps
generate
fluid flow by directly
exerting forces on the liquid without involving any structural
movement. These systems convert a non-mechanical energy source
into kinetic energy and typically have a limited flow rate and slower
response compared to mechanical micropumps. They often require
interaction with a working solution possessing specific electrical
properties, such as conductivity. Despite these limitations,
non-mechanical micropumps are valuable in drug delivery applications due to their low power consumption. Common actuation
methods include electro-hydro-dynamic, magneto-hydrodynamic,
electro-osmotic, and electrochemical forces, with electrochemical
forces being particularly relevant for drug release applications.
Another g
roup o
f MEMS devices for drug release applications
utilizes multiple reservoirs, each designed to deliver a single dose of
the loaded drug. These devices employ various actuation mechanisms to achieve precise and controlled release by promoting the
dissolution or rupture of the reservoir capping membranes. Notably, an implantable multi-reservoir device was developed for passive
release of chemotherapeutic drugs to test tumor sensitivity in vivo.
This device,
implanted through a biopsy needle, directly delivered drugs into tumor tissue without systemic exposure, using
micromachined Delrin acetal resin blocks with 3–30 circular reservoirs for passive drug release over 24 h. Techniques such as modifying reservoir opening size, using polymer matrices to control
drug diffusion, and employing hydrophilic hydrogels to eject

Biosensor-Based Drug Delivery Systems: Innovations, Applications, and… 233
Table 2
Multi reservoir-based MEMS devices for drug delivery applications
Working
S.
Drugs loaded
no.
mechanism
of MEMS
Materials used Dimensions Ref erence
1. Human growth hormone NIR
irradiation
2. Doxorubicin, sunitinib,
lapatinib, antibody
cetuximab, dasatinib,
gemcitabine, paclitaxel,
cisplatin
3. Human parathyroid
hormone fragment
(1–34) [hPTH(1–34)]
4. Mannitol Electrothermal Silicon wafer
Passive release Delrin acetal
Electrothermal Titanium
Graphene
oxide
nanoparticles
Polyurethane
medical
epoxy
Parylene C
resin blocks
housing
silicon wafer
Ti-Pt
Au or
Pt/Ti/Pt
membranes
drugs were employed to control the release profile. Additionally,
combining drugs in a single reservoir allowed testing of up to
16 drug combinations, enabling optimization of drug therapy
before systemic treatment. Table
wide using multi reservoir-based MEMS.
27 mm × 11.5 mm
× 9.5 mm
820 μm × 3 mm [12]
13 × 5.4 × 0.5 mm [13]
Not specified [14]
[11]
2 summarizes work done world-
2.1.2 Smart Polymers
Smart polymers are the materials that mimic biological systems,
undergoing structural changes in response to external stimuli
such as pH, temperature, and ionic variations can also be used as
biosensors. These polymers are categorized into three forms based
on their physical properties: linear free chains in solutions collapse
reversibly upon stimulus application; covalently cross-linked reversible gels swell or shrink in response to environmental changes; and
chain adsorbed or surface-grafted polymers exhibit reversible
swelling or collapse on surfaces when triggers are altered [
They have
the ability to deliver drugs when needed. One such
15, 16].
example is the attachment of both glucose oxidase and insulin
within a hydrogel that is responsive to changes in pH, enabling
this smart polymer to act both as a sensor of glucose concentration
and as a drug delivery vehicle for insulin [
17]. These types of

234 Disha Pant et al.
biosensor-drug delivery systems can reduce the risk of overdosing/
underdosing a patient while allowing the patient to receive the drug
at a specific time point.
2.1.3 Microfabricated Devices
Most microfabricated devices function as biosensors, but their
utility is often restricted by a short lifespan. Designing implantable
biosensors with extended functionality is critical for optimal closedloop drug delivery or monitoring systems. Addressing challenges
such as implant biocompatibility and biofouling is essential for
maintaining long-term in vivo sensing.
Enhancing the integration of drug delivery systems with biosensor technology can be achieved using hydrogels sensitive to
thermal, pH, ionic strength, or biomolecular changes. These materials improve biocompatibility and reduce biofouling.
Innovatively, a cantilever can act as a lid on reservoirs, where a
responsive hydrogel containing sensing molecules can control the
lid’s opening and closing based on analyte levels. Electrically
responsive hydrogels can also be used in MEMS-based sensors or
drug delivery devices, enabling external electrical stimulation to
trigger drug release.
MEMS technology has been utilized to create microparticles
and micro-reservoirs for drug delivery. Microparticles are produced
by forming arrays of wells, 25–100 μm in size, within silicon squares
measuring 80–150 μm. These wells are filled with drugs and sealed
with dissolvable caps that adhere to target sites due to bioadhesive
properties, allowing precise drug delivery. Smart polymers capable
of shrinking upon analyte detection can enhance these microparticles, enabling responsive drug release and integration with
biosensors.
For example, micro-reservoirs are made from silicon and
capped with gold membranes that rupture upon voltage stimulation. Instead of voltage, smart polymers can collapse in response to
analyte concentrations or use conductive polymers activated during
redox reactions. Overall, microfabricated devices have revolutionized the development of controlled-release microchips [
Lab-on-a-chip s
ystems h
ave the edge of rapid and improved
2].
data analysis, and portability of the devices, allowing point of care
diagnosis and treatment. Incorporation of a micro-reservoir drug
depot, micro-pump, valves, and sensors onto BioMEMS devices
allowed responsive and controlled release of drug. This increases
bioavailability and reduces incidences of toxicity.
A new
controlled-release microchip has been developed using
silicon wafers and various drug reservoirs for both single and multiple drug release [
18]. By incorporating drug-loaded hydrogels,
biosensors, and responsive elements, these devices can interact
more seamlessly with biological environments. This integration
allows pharmaceutical devices to operate more autonomously
within their surroundings, reducing the need for constant human
oversight.

Biosensor-Based Drug Delivery Systems: Innovations, Applications, and… 235
Microchips are manufactured using MEMS technology by initially choosing a biocompatible substrate and etching microreservoirs to contain therapeutic solutions. The next step involves
selecting a conductive sealant, a thin membrane that doubles as an
anode. The membrane is specifically chosen to maintain structural
integrity in a solution without an applied electrical potential, preventing dissolution or rupture.
When considering in vivo implantation, it is crucial to account
for the presence of oxygen and chloride ions, which can cause metal
corrosion. Microchips offer numerous advantages, such as the ability to pattern multiple micro-reservoirs for holding various drugs.
This design prevents mechanical breakdown or drug leakage that
may occur due to incomplete lid closure, as there are no moving
parts, unlike glucose biosensors. Moreover, microchips eliminate
the need for patient or doctor intervention to ensure functionality
and can support closed-loop systems when integrated with biosensors. Designing disposable chips can further enhance both biosensor and drug delivery systems [
2].
2.2 BioreceptorBased Biosensors
2.2.1 Enzyme-Based Biosensors
2.2.2 Antibody-Based Biosensors
Based upon the bioreceptors, biosensors are categorized as follows.
These are most common biosensors utilized for detection of fluctuating glucose and urea levels in the body. The working principle
of an enzyme-based biosensor depends on the catalytic reaction and
binding capabilities for the target analyte detection. The concentration of enzyme-based biosensors alters depending upon the
catalytic transformation of the analyte by the enzyme, inactivation
or activation by analyte, and tracking of the alteration of enzyme
characteristics. However, the enzyme structure is extremely sensitive, which makes it expensive and complicated to improve its
sensitivity, stability, and adaptability [
19].
These have an embedded antibody as ligand or they function on the
antibody–antigen interaction is called immunosensors.
Non-labeled immunosensors are constructed to specifically determine the antigen–antibody complex by estimating the physical
changes caused by the development of the complex. In the case of
labeled immunosensor, a sensitively detectable label is introduced.
Madurro et al. constructed a label-free immunosensor to detect
ovarian cancer. The system has a linear relationship of anti-CA125
concentration in the range of 5–80 U mL
detection of 1.45 U mL
-1
[19].
-1
, exhibiting a limit of
2.2.3 Aptamer-Based Biosensors
These biosensors utilize aptamers which are synthetic singlestranded nucleic acids (sequences of DNA or RNA) that bind to
target molecules selectively and can be folded into two-dimensional
(2D) and three-dimensional (3D) structures. In 2D or 3D

236 Disha Pant et al.
structures, the targets have high-binding performance due to
greater surface density and less spatial blocking. Due to the nucleic
acid character of aptamers, they are structurally and functionally
stable over a wide range of temperatures and storage conditions.
Unlike antibodies that require biological systems to be generated,
aptamers can be chemically synthesized, are stable in a pH range of
2–12, and have certain thermal refolding capabilities. A further
benefi
t of aptamers is that they can be chemically modified accord-
ing to the detection
criteria for the target molecule.
By an in vitro selection mechanism, SELEX (Systematic Evolution of Ligands by EXponential enrichment), aptamers can be
isolated from oligonucleotides libraries. Several SELEX variants
have recently been established, including cell- SELEX, capillary
electrophoresis-based SELEX, microfluidics-SELEX, FACS-based
SELEX, microtiter plate-SELEX, magnetic bead SELEX, and
in vivo SELEX. Optical, electrochemical, and piezoelectric techniques are the most frequently used in biosensors [
Depending on
dif
ferent transduction techniques, these biosen-
19].
sors are further categorized as labeled or label-free aptasensors.
Surface plasmon resonance (SPR) is the most commonly used
method for the label-free optical sensors, whereas fluorescent dyes
(fluorescein) are used for label-based optical aptasensors. For tracking biological systems in real time, fluorescent NPs, such as QDs,
provide many benefits over regular fluorescent dyes. To identify
targets, such as cancer cells, bacterial spores, and proteins, aptamerQD conjugates were used. Aptamer capped NIR PbS QDs have
been designed to detect thrombin protein, based on selective
charge transfer, within 1 min and with a detection limit of ~1 nM.
Gold nanoparticles (GNPs) have demonstrated interesting absorption characteristics that vary depending upon their aggregation
state. Furthermore, GNPs are more biocompatible, easier to bioconjugate, and less toxic than QDs [
19].
2.2.4 Whole-Cell-Based Biosensors
These utilize microbes (bacterial, fungi (yeasts and molds), algae,
protozoa, and viruses), since they possess potential biorecognition
elements, in the construction of whole-cell-based biosensors. They
are self-replicating and can produce recognition elements, such as
antibodies, without the need for extraction and purification. Compared with animal or plant cells, whole-cell-based biosensors are
easy to handle and rapidly proliferating. The cells can interact with a
wide variety of analytes, display the electrochemical response that a
transducer can register, and can transmit (whole-cell-based biosensor principle). Owing to their good sensitivity, high selectivity, and
capability of detection, these biosensors were successfully employed
in environmental monitoring, food analysis, pharmacology, heavy
metals, pesticides, detection of organic contaminants, and drug
screening. A label-free optical whole-cell Escherichia coli biosensor

Biosensor-Based Drug Delivery Systems: Innovations, Applications, and… 237
2.2.5 NanoparticleBased Biosensors
has been developed to detect pyrethroid insecticide exposure
with a detection limit of 3 ng mL
0.01–2 ng mL
-1
[19].
-1
in the linear range of
Nanobiosensors operate on a similar principle to their conventional
macro- and micro-scale counterparts but are built using nanoscale
components for signal or data transformation. They of fer unique
advantages over larger counterparts due to their multidisciplinary
applications enabled by their nanoscale dimensions.
They are particularly valuable for electrode modification, where
they enhance the sensitivity and specificity of electrochemical catalysis. Additionally, catalytically active nanomaterials, such as transition metal oxides, have been engineered into nanoenzymes,
enabling catalysis of biochemical reactions directly on biosensors.
To enhance NP biosensing performance, they are often coated
with various matrices such as metal oxides, silica networks, polymers, graphene, fibers, and dendrimers. These coatings serve to
improve stability, increase specificity, and enhance sensitivity, tailoring the NPs for specific biosensing applications.
Over the past decade, metal oxide-based nanomaterials have
found extensive applications across various domains such as electrochemistry, magnetism, catalysis, and sensor technology due to
their diverse electrical, chemical, and physical properties. Among
the commonly utilized metal oxide nanoparticles are copper oxide
(CuO), nickel oxide (NiO), iron oxide (Fe
(Co
oxide (TiO
num oxide (MoO
), manganese oxide (MnO2), zinc oxide (ZnO), titanium
3O4
), tin oxide (SnO2), cadmium oxide (CdO), molybde-
2
), and cerium oxide (CeO2). These nanoparticles
3
), cobalt oxide
2O3
exhibit outstanding optical, electronic, magnetic, chemical,
mechanical, and catalytic properties.
Gold nanoparticles (NPs), classified among noble metal NPs,
are extensively studied and utilized due to their remarkable optical,
electronic, and physicochemical properties. They hold significant
advantages in biomedical research, including simple synthesis techniques, straightforward fabrication procedures, high chemical stability, biocompatibility, wide electrochemical potential range, high
catalytic activity, and versatility in nanocomposite forms.
Palladium n
anopart
icles (Pd NPs) offer intriguing potential for
biomedical applications due to their high catalytic and sensing
activities. Additionally, palladium (Pd) is more abundant than
gold (Au) and platinum (Pt), rendering it cost-effective and versatile for various sensing applications.
Copper (Cu)
has garnered significant attention as a promising
sensing material due to its outstanding electrical conductivity, stability, electrocatalytic properties, and cost-effectiveness compared
to noble metals. Recently, Huang et al. investigated electrochemical
glucose sensors based on copper nanoparticles (Cu NPs) loaded
onto a flexible graphite sheet.

238 Disha Pant et al.
Table 3
Heavy metal-based nano-biosensors
S.
Metal-based
No
nanopartic
1. Titanium
dioxide
2. Zinc oxide Carbon monoxide gas 80 ppm [21]
3. Manganese
dioxide
4. Nickel oxide Glucose biosensors Detection limit (5.0 × 10
5. Cobalt oxide Glutamate biosensor chip Detection limit of 10 μM. [25]
les Molecule detected Detection limit Reference
Detection of Salmonella
typhimurium
Glucose biosensor Detection limit of 0.05 mmol L
Urea biosensor 1 × 10
Detection of miRNA-141 1 pM to 50 nM and a detection limit of
103 –105 cL mL
high sensitivity of 56.32 μA mmol
-2
1
cm
Detection limit of 0.51 μM with a linear
range
-4
0.2
pM
-1
-10
of 1 μM to 2 0mM
-2
and 8 × 10
M[
-1
and
-
M) [23]
[20]
[22]
[24]
26]
[27]
6. Iron oxide Anticancer drugs tagged to
superparamagnetic
ticles
7 Gold-nickel
bimetallic
nanopar
Non-enzymatic glucose
sensor
Furthermore, metal oxide-based nanoparticles such as ZnO,
, SnO2, and MoO3 have recently gained significant attention
TiO
2
for their versatile applications. ZnO nanoparticles are known for
their good electron transfer rate, stability, biocompatibility, and
high conductivity. Table 3 shows a list of heavy metal based nanobiosensors
synthesized for detection of biomolecules.
3 Methods
A typical biosensor comprises of five essential components, viz., an
analyte, a bioreceptor, a transducer, electronics, and display. An
analyte is a molecule whose levels are to be identified. It can be
glucose, calcium, or any other biomolecule which acts as a substrate
to its respective bioreceptor-like enzymes, antibody, cells, aptamers,
nanoparticles, etc., The tranducer then generates signals (optical/
electrical) in proportion to the intensity of analyte bioreceptor
interaction (biorecognition). The electrical signals obtained from
the transducer are amplified, processed, and quantified by the
display unit and made readable at user’s end. Figure 3 expresses
the co
mplete picture of the components for a biosensor system.
Glucose (1–1900 μM) and a low
detection
limit (0.063 μM)
[28]
[29]
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