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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5640_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

Introduction to Drug Delivery System: Past, Present, and Future Perspectives 9
Liposomes, derived from the term “lipid body,” are microscopic spherical vesicles composed of one or more concentric lipid
bilayers, with water or aqueous buffer compartments in between,
and diameters ranging from 25 nm to 10,000 nm. These structures
form through the self-assembly of phospholipid molecules in an
aqueous environment. Liposomes typically consist of one or more
amphiphilic phospholipid bilayer membranes, also known as phospholipid vesicles, capable of encapsulating both hydrophilic and
hydrophobic drugs. Hydrophilic drugs are enclosed within the
aqueous center of the liposome, while the phospholipid membrane
comprising the liposome’s wall can accommodate hydrophobic
agents.
Sphingosomes can be described as vesicles with concentric,
bilayer structures where an aqueous compartment is completely
enclosed by a lipid bilayer primarily made up of natural or synthetic
sphingolipids. These sphingosomes can be administered through
various routes, including parenteral routes such as intravenous,
intramuscular, subcutaneous, and intra-arterial methods.
Transfersomes represent a recent advancement in drug delivery
systems and are a specialized form of liposomes. They consist of
phosphatidylcholine along with an edge activator. These structures
possess an extremely flexible membrane, enabling them to consistently deliver drugs either into or through the skin. The effectiveness of drug delivery using this system depends on the method of
administration or application chosen. Transferosomes exhibit significantly greater elasticity and flexibility compared to conventional
liposomal drug delivery systems. This enhanced flexibility facilitates
efficient penetration of the skin, making transferosomes a
promising option for novel drug delivery systems. They are essentially highly adaptable and optimized mixed lipid complexes.
Niosomes r
epresent a
n innovative drug delivery approach
where the medication is enclosed within a vesicle. These vesicles
are constructed from a bilayer of non-ionic surface-active agents,
giving rise to their name “niosomes.” Niosomes are characterized
by their minute size, falling within the nanometric scale, making
them microscopic.
Ethosomes are
liposomes containing ethanol. They serve as
noninvasive carriers facilitating the penetration of drugs into deep
skin layers or systemic circulation. Ethosomes are flexible vesicles
designed to enhance the delivery of active agents. These vesicles
have long been recognized for their significance in cellular communication and particle transport. Additionally, they enable the control of drug release rates over extended periods, protecting the drug
from immune responses or elimination systems. Consequently, they
can maintain optimal drug concentrations for prolonged durations.

10 Santanu Pal et al.
5 Recent Drug Delivery Systems
5.1 Red Blood Cell
MembraneCamouflaged
Nanoparticles Drug
Delivery System
5.2 Hyaluronic AcidBased Drug
Nanocarriers Drug
Delivery Systems
The inherent properties and biological importance of red blood
cells (RBCs) make them an effective choice for concealing nanoparticles and serving as a camouflage material. Due to their abundance as the most prevalent circulating cells in the body, red blood
cells (RBCs) possess biocompatibility, biodegradability, and an
extended circulating half-life, rendering them well suited as an
optimal carrier for drug delivery. Numerous approaches have
been devised to load therapeutic substances onto red blood cells
(RBCs) while preserving their structural integrity and physiological
functions. Coated nanoparticles are designed to imitate RBCs,
allowing for prolonged systemic circulation upon injection and
interaction with the surrounding environment. Sonication stands
out as the predominant technique for producing
RBC-camouflaged nanoparticles. Alter native methods for
combining RBCs with nanoparticles include in-situ polymerization, microfluidic electroporation, and extrusion. The utilization
of RBCM-NP drug delivery systems holds great promise and presents several advantages, primarily stemming from their minimal
immunogenicity and capacity for sustaining prolonged systemic
circulation, lasting up to 120 days.
Hyaluronic acid represents a novel polymer suitable for crafting
medication delivery systems. This linear macromolecular mucopolysaccharide consists of interconnected glucuronic acid and
N-acetylglucosamine saccharide units. It possesses attributes such
as biocompatibility, biodegradability, and high viscoelasticity, and it
can bind to specific cell surface receptors. Given its natural presence
in eye tissue and its role in wound healing, utilizing hyaluronic acid
as a carrier for ocular drug delivery seems logical, provided that it
ensures consistent release of the incorporated pharmaceuticals. The
use of active targeted hyaluronic acid (HA)-based drug nanocarriers has significantly enhanced drug distribution to cancer cells.
Furthermore, lipid nanoparticles coated with appropriate HA have
been engineered as biocompatible drug carriers, showing
promising potential for targeted drug delivery to specific tissues
while mitigating side effects on other tissues. Employing HA-based
nanocarriers for cancers exhibiting elevated CD44 receptor expression offers several advantages, including enhanced drug delivery,
improved therapeutic effectiveness, heightened cytotoxicity, a notable reduction in tumor growth, and considerable potential for
targeted chemotherapy.
5.3 Hexagonal Boron Nitride Nanosheet Drug Delivery System
Jedrzejczak-Silicka and her team have demonstrated the utility of
hexagonal boron nitride (H-BN) in drug research and delivery
systems. Their study revealed a decrease in the proliferation of

Introduction to Drug Delivery System: Past, Present, and Future Perspectives 11
MCF-7 cell line cultures compared to normal L929 cell lines when
exposed to H-BN loaded with gold particles. The process involved
exfoliating H-BN through chemical treatment using a modified
Hummers’ method and sonication treatment, followed by functionalization with gold particles for analysis using the neutral red
(NR) uptake assay.
5.4 Polymer-Lipid Hybrid Nanoparticles Drug Delivery System
5.5 Self-Micro Emulsifying Drug Delivery System
This hybrid system successfully meets various criteria including
biocompatibility, long storage stability, sustained drug release, minimal drug leakage, small particle size, and efficient encapsulation.
Due to its effectiveness, this system is currently utilized for diverse
therapeutic purposes and diagnostic applications. PLHNPs consist
of three key components: a polymeric core capable of effectively
encapsulating both hydrophilic and hydrophobic drugs due to its
dual nature, resulting in sustained release; a lipid shell ensuring
biocompatibility and high stability; and a lipid-polyethylene glycol
(PEG) outer layer covered by a lipid shell, enhancing steric stability,
preventing immune recognition, and prolonging circulation time.
PLHNPs find wide-ranging applications in delivering various chemotherapeutic agents, and gene transfer (siRNA, DNA), as well as
in photothermal, photodynamic therapy, and ultrasound
applications.
Lipid-based carriers are available in various forms, including suspensions, dry emulsions, microemulsions, and self-emulsifying
drug delivery systems (SEDDS) (Table 3). SEDDS have been
recognized for their capability to incorporate hydrophobic dr ugs.
SEDDS has evolved into self-micro emulsifying drug-delivery systems (SMEDDS) and self-nano emulsifying drug delivery systems
(SNEDDS). Emulsions, on the other hand, are formed by
Table 3
Important categories of lipid-based drug delivery systems (LBDDS) along with their advantages and
disadvantages
Sl. No. Characteristics SMEDDS SNEDDS SEDDS
1. Size of the globule <250 nm <100 nm >300 nm
2. The system appearance High optical clarity High optical clarity Cloudy
3. The surfactant HLB value >12 >12 <12
4. LFCS classification Type IIIB Type IIIB Type II
5. Oil phase >20% >20% 40–80%
6. Surfactants concentration 40–80% 40–80% 30–
Key: HLB hydrophilic/lipophilic balance; LFCS lipid formulation classification system; SEDDS Self-emulsifying drugdelivery systems; SMEDDS self-microemulsifying drug-delivery systems; SNEDDS self-nanoemulsifying drug-delivery
system
40%

12 Santanu Pal et al.
dispersing a liquid phase containing macroscopic particles into a
different liquid phase–containing surfactant. They represent a thermodynamically unstable solution that appears semi-transparent
(occasionally hazy) and exhibits properties resembling viscous
liquids. Emulsions come in three types: water-in-oil, oil-in-water,
and multiple emulsions. Moreover, conventional micro- or nanoemulsions differ from SMEDDS in that they self-emulsify followi
ng
oral ingestion.
5.6 In Situ Gel Drug Delivery System
5.7 Microelectromechanical Systems
(MEMS) for Drug
Delivery
The in situ gel drug delivery system has emerged as a highly
innovative approach to medication administration. Its distinctive
property of transitioning from a solution to a gel enables prolonged
and controlled release of medications, along with enhancing patient
compliance and comfort. Typically, formulations in solution form
undergo a transition into gel form under specific physiological
conditions before administration. Various stimuli, including pH
alterations, temperature changes, and solvent exchange, contribute
to this transfor mation from solution to gel form. Four mechanisms
are recognized for generating in situ gel biomaterials, including
temperature and pH fluctuations, alterations in the physical characteristics of biomaterials such as solvent exchange and swelling,
biochemical modifications like enzymatic and chemical reactions,
and photo-polymerization.
This technology
utilizes microfabrication techniques to create
micro-/nano-scale electromechanical and mechanical devices or
implants. MEMS-based devices are designed using a wide array of
materials and processes, with the most commonly employed
approach involving a creative combination of different micromachining techniques. These techniques include deposition
(an additive process), etching (a subtractive process), lithography
(a patterning process), ink jetting, ion implantation, oxidation, and
micro molding. In drug delivery systems, MEMS technology constructs miniature systems composed of diverse materials such as
silicon, glass, metals, nitrides, and polymers. These systems may
incorporate micropumps, sensors, microvalves, reservoirs, actuators, and high-performance processors. MEMS-based devices are
crucial for achieving targeted and precise drug delivery through
controlled and pulsatile release of enclosed pharmaceuticals. These
devices can be designed as either electric-powered or non-electricpowered systems. Electric-powered devices enable selective drug
release from reservoirs via electric potential, whereas non-powered
devices utilize diffusion and osmotic environmental stimulus
mechanisms to facilitate drug release. Among MEMS technologies
applicable in drug delivery, microchips are the most widely utilized,
followed by microfluidic devices, particularly micropumps. Drug
delivery devices produced through MEMS technologies present
numerous advantages compared to traditional delivery methods.

Introduction to Drug Delivery System: Past, Present, and Future Perspectives 13
These include improved performance, automation, precision, and
efficacy resulting from the integration of miniaturized sizes with
multifunctional components. Moreover, MEMS-based devices
contribute to reduced pain and invasiveness during use. Additionally, they enable drug stability maintenance during encapsulation,
adjustable and continuous delivery, and facilitate the automated
release of multiple drugs from reservoirs.
5.8 Targeted Drug Delivery
The demand for targeted drug delivery (TDD) over conventional
drug delivery systems (DSS) stems from four key factors: the inadequate per formance of drugs concerning pharmacodynamic, pharmacokinetic, pharmaceutical, and pharmacotherapeutic aspects
with conventional delivery methods (Fig.
4). Delivering drugs to
specific areas using optimized drug delivery methods is essential not
only for improving therapeutic effectiveness but also for minimizing toxicity linked to drugs with a narrow therapeutic index and
high doses. Targeting is necessary to address the limitations and
inherent drawbacks of conventional drug delivery systems (DDSs).
Parenteral delivery is invasive, oral administration is unsuitable for
protein- or peptide-based drugs, and topical creams and ointments
are primarily restricted to local effects. Moreover, the efficacy of
drug-target interactions is diminished unless the drug is transported to its intended site of action at a dosage and rate that
minimizes side effects while maximizing therapeutic benefits
7]. Moreover, simpler drug administration processes, reduced
[
drug quantities leading to lower therapeutic costs, and the ability
to significantly enhance drug concentration in target areas without
adversely affecting non-target areas are all promising advantages of
targeted drug delivery (TDD). Overall, drug targeting results in
improved effectiveness, regulated pharmacokinetics, controlled
Fig. 4 The illustration of the necessity for targeted drug delivery over conventional drug delivery systems

14 Santanu Pal et al.
distribution throughout the body, heightened specificity in localization, decreased toxicity, lowered dosage requirements, and
enhanced patient adherence to treatment regimens.
The fundamental concept of drug targeting involves delivering
a concentrated amount of dr ug to the intended site while minimizing its presence in non-targeted areas. This approach helps maximize the therapeutic effects of the dr ug while reducing side effects
resulting from interactions with multiple targets, high doses, and
unintended concentrations in non-targeted regions. Additionally,
targeting helps mitigate unwanted interactions between the drug
and biological environmental factors that may hinder its access to
targeted sites within the body. Drug targeting involves the synchronized actions of the drug, the target site, and the pharmaceutical
carrier. The target refers to the particular organ, cell, or group of
cells, either in a chronic or acute condition requiring treatment,
with which the drug will interact. The carrier is a specially designed
molecule or system crucial for efficiently transporting the loaded
drug to predetermined sites. Ideally, a drug-targeting complex
should be non-toxic, non-immunogenic, biochemically inactive,
biodegradable, biocompatible, and exhibit stability both in vivo
and in vitro. To ensure that these ideal characteristics are met,
targeted drug products should be formulated while taking into
account the unique proper ties of target cells and the characteristics
of transport carriers or vehicles responsible for delivering the drug
to specific receptors. While targeted drug delivery (TDD) can
address various chronic and infectious diseases, its primary significance lies in cancer treatment, attributed to its improved penetration of tumors and enhanced concentration at the infection site.
Promising applications and objectives of TDD encompass cancer
therapy, vaccine enhancement, delivery to ocular and brain regions,
DNA and oligonucleotide transport, targeting intracellularly and
systemically, administering orally and transdermally, conducting
enzyme immunoassays, and performing radioimaging.
Dru
argeting can be categorized into three (or four) distinct
g t
levels of targeting. First-order targeting involves restricting the
distribution of the drug-carrier system to the capillary bed of the
target site. Second-order targeting entails delivering drugs selectively to specific cell types, such as tumor cells. Third-order targeting focuses on directing drugs to intracellular sites specifically, while
fourth-order targeting is occasionally referred to as drugs targeting
macromolecules like DNA and proteins.
Physical targeting
involves systems that concentrate agents in
target regions due to their size, composition, or other inherent
characteristics, rather than being specifically designed for a
biological receptor. Chemical targeting entails directing agents to
targeted areas using site-specific prodrugs. Agents can also be
guided to specific areas through enzymatic or chemical reactions,
leading to the targeting of a vehicle or the controlled release or

Introduction to Drug Delivery System: Past, Present, and Future Perspectives 15
action of the agent. Biological targeting allows localized agents to
concentrate in target areas using antibodies (Abs), peptides, proteins, or other biomolecules that possess affinity with receptors,
sites, or other biological targets in a specific manner. Gene expression can also be localized to target areas using cells, tissue, or
specific promoters within vector systems.
Locally targeted systems are noninvasive targeting approaches
primarily aimed at delivering drugs to a specific local site to manage
local pathologies. In contrast, systemic targeting involves delivering
therapeutic systems via an invasive route, such as intravenous
administration of nanotechnological systems. These systems distribute the drug throughout the body via systemic circulation.
The primary limitations of systemic targeting stem from the adverse
effects of drugs on nonspecific tissues.
Targeted drug delivery (TDD) employing location-based strategies involves delivering drugs to specific cells, organs, and organelles. Examples of location-based targeting include intracellular
targeting, gastrointestinal tract (GIT) targeting, brain targeting,
and targeting the respiratory tract. Intracellular delivery of pharmaceutical agents, such as proteins, antibodies (Abs), and drug-loaded
nanocarriers, ensures that therapeutic action is specifically directed
to the nucleus or specific organelles. Floating drug delivery
(DD) exemplifies this targeting approach, where antiviral, antifungal, and antibiotic agents are absorbed from specific regions of the
GIT. Various site-specific oral controlled-release systems have been
developed to target the stomach/duodenum, small intestine,
lymph nodes, and colon. Polymer-based drug delivery systems
(DDSs), such as dopamine-liposome conjugates, demonstrate
effective brain targeting with reduced degradation during circulation. Additionally, disease-based targeted delivery involves sitespecific therapy targeting tumors and other treatable infectious
diseases.
6 Ceramic-Based Drug Delivery System
Ceramic materials possess numerous desirable properties, including
ease of preparation, adjustable size and structure, high surface area
to volume ratio, stability under physiological conditions, and excellent biocompatibility (Fig.
utilized in the field of drug delivery systems (DDS) for many years,
serving as drug carriers. Traditional ceramic materials are comprised of inorganic solid compounds, primarily consisting of carbides, and oxides such as hydroxyapatite, tricalcium phosphate,
silica, zeolite, and zirconia. The need for effective dose requirements (ED50) may diminish due to the enhanced delivery efficiency of controlled, sustained, and targeted drug delivery
systems (DDS), potentially leading to cost reductions for patients.
Consequently, they have been widely
5).

16 Santanu Pal et al.
Fig. 5 Ceramic-based drug delivery system working on the principle of using ceramic materials to encapsulate
and release therapeutic agents in a controlled manner
There is a growing demand for local, homogeneous, controlled,
and sustained drug release [
17]. Therefore, it is crucial to develop
carriers with adjustable size and structure, favorable stability under
physiological conditions, excellent biocompatibility, and high
uptake efficiency. In this regard, ceramics emerge as an attractive
material choice for carriers.
Ceramic-based drug carriers have garnered growing interest
alongside advancements in medicine, pharmaceutics, and material
science. Prominent bioceramics include beta-tricalcium phosphate
(β-TCP), hydroxyapatite, mesoporous silica, and zirconia hydroxyapatite composite, among others. Additionally, bioceramics constitute integral components of certain inorganic-organic composites
employed as drug carriers. The benefits of ceramic-based drug
carriers include the following:
1. They offer adjustable size and structure, making them suitable
for accommodating nano-sized drugs.
2. They exhibit low toxicity, as ceramics typically possess good
biocompatibility, biodegradability, and biological stability.
3. Certain ceramics demonstrate sensitivity to environmental factors such as light, magnetism, or heat, allowing them to
respond accordingly.
7 Polysaccharide-Based Drug Delivery System
Numerous surface coatings derived from polysaccharides have been
suggested to confer antimicrobial attributes to implantable materials, primarily metals and polymers. Medical surface functionalization with antimicrobial agents provides an alternative to
conventional drug delivery methods. This delivery system can be
employed for systemic and topical applications and can be

Introduction to Drug Delivery System: Past, Present, and Future Perspectives 17
administered through various routes, including oral, buccal, sublingual, ocular, and transdermal, based on the intended purpose.
Hence, designing effective coatings requires a comprehensive
understanding of the pharmacological characteristics of drugs and
polysaccharides, along with a careful selection of manufacturing
techniques. Polysaccharides serve various functions, including facilitating rapid drug absorption in the gastrointestinal tract or
ering dr
suitable for drugs with high mucosal permeability, commonly utilized in buccal and sublingual delivery methods. Ophthalmic coatings are primarily employed to treat anterior segment diseases.
Orodispersible films, also known as soluble films, dissolve quickly
in the oral cavity. Fast-dissolving oral films have very thin dimensions and dissolve within a minute in the mouth. Buccal adhes
films deliver
circulation post-absorption. Wafers are thin polymeric films used as
carriers for pharmaceutical agents and do not require water for
drug absorption. Polysaccharide coatings are also applied for surface modification of medical devices, particularly in prosthetic
applications for orthopedics and dentistry, enabling controlled
drug release. Thin films for drug delivery can be formulated
throug
saccharide thin
integral components during preparation [
ugs directly to the administration site. They are particularly
drugs directly through the buccal mucosa for systemic
h two methods: loading drugs directly onto pre-made poly-
films or creating thin films by incorporating drugs as
8].
deliv-
ive
8 Closed Loop Insulin Delivery System
Glucose-responsive insulin delivery systems had their beginnings in
the 1960s and 1970s when early versions relied on venous glucose
readings to regulate intravenous infusions of insulin and dextrose to
keep blood sugar levels stable. It’s only in recent years that these
large, stationary technologies have evolved into compact, wearable
devices. Today’s closed-loop systems utilize interstitial glucose
monitoring, insulin pumps implanted under the skin, and advanced
algorithms to manage blood sugar levels more effectively [
early 1960s, Arnold Kadish pioneered the first closed-loop insulin
delivery system. Kadish’s creation, referred to as a “servomechanism for blood glucose control,” consisted of an autoanalyzer for
ongoing monitoring of blood glucose levels through an intravenous catheter. Additionally, it included two intravenous syringe
pumps containing insulin and either glucose or glucagon [
2005, the Juvenile Diabetes Research Foundation (JDRF) initiated
the Artificial Pancreas Project. The primary goal of this endeavor
was to support research, facilitate regulatory approval processes,
and ultimately encourage the widespread adoption of closed-loop
technologies for diabetes management [
(LGS) systems represent the most basic form of closed-loop
Low-glucose suspend
17].
9]. In the
17]. In

18 Santanu Pal et al.
systems. These systems are comprised of a combined glucose sensor
and insulin pump, which can autonomously halt insulin infusion
when blood glucose levels drop below a predetermined threshold,
without needing confirmation from the user. The advancement of
LGS technology led to the development of predictive low-glucose
suspend (PLGS) systems. These systems incorporate algorithms
capable of forecasting impending hypoglycemia, such as within
the next 30 minutes, an
the onset
designed to mitigate both hypoglycemia and hyperglycemia by
regulating glucose levels within a specified target range. These
systems employ a computerized algorithm to modify the basal
insulin rate and administer corrective bolus doses as needed. They
are termed “hybrid” systems because, unlike fully closed-loop systems, users are still responsible for manuall
boluses when
opposed to hybrid systems, are engineered to automate insulin
delivery entirely, eliminating the need for user input regarding
mealtime boluses. The primary obstacle in fully closed-loop systems
lies in managing postprandial hyperglycemia, given the absence of
manually provided data regarding meal timing and carbohydrate
intake. These instances of postprandial glucose elevation f
lead to
current rapid-acting insulins. Two early closed-loop systems, pioneered by Kadish and Shichiri, employed a dual-hormone strategy,
utilizing both insulins to counteract hyperglycemia and glucagon
to counteract hypoglycemia. However, the use of glucagon in
closed-loop systems became less common during the Biostator era
and only reappeared in subcutaneous closed-loop systems in
research ar
hormone
alongside continuous insulin infusion, stems from the notion that
preventing hypoglycemia is more effective through glucagon
administration rather than suspending insulin delivery. This is primarily due to the pharmacokinetic properties of subcutaneous
insulin and glucagon: currently, available rapid-acting insulins
have a relatively slow onset
reach maximum
of action (up to 4–6 hours), whereas glucagon exhibits a rapid
onset within 5 minutes [
of hypoglycemia. Hybrid closed-loop systems are
consuming meals. Fully closed-loop systems, as
subsequent hypoglycemia due to the delayed effects of
ound the mid-2000s. The main rationale behind dualsystems, capable of administering glucagon boluses
effect (40–60 minutes), and extended duration
d proactively pause insulin delivery before
y inputting insulin
requently
(10–15 minutes), delayed time to
.
17]
9 Liposome-Mediated Drug Delivery
Liposomes are tiny vesicles containing an aqueous core surrounded
by a lipid bilayer membrane. A.D. Bangham and R.W. Thorne
initially observed these structures in 1964 through electron microscopy while studying the dispersion of phospholipids in water. They
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