Introduction to Nanotechnology

Nanotechnology

• The branch of science dealing with structures on the nanoscale, measuring 1-100 nanometers
• Includes disciplines like Physics, Chemistry, Biology, Engineering, Information Technology, Electronics, and Material Science
• Nanoparticles possess distinct material properties due to their submicroscopic size
• Widely used in various fields, including engineering, drug delivery, nanomedicine, environmental identification, and catalysis
• Effectively targets diseases like melanoma, cardiovascular disease, skin diseases, and liver diseases

History of Nanotechnology

• Polymers and drug conjugation was first reported in 1955
• The first controlled-release polymer device was developed in 1964
• Liposomes were discovered in 1965
• Albumin-based nanoparticles were reported in 1972
• Liposome-based drugs were formulated in 1973
• The first micelle formulation was approved in 1983
• The FDA approved the first controlled formulation in 1989
• The first polyethylene glycol (PEG) conjugated protein entered the market in 1990

Recent Approaches in Drug Delivery System

• Nanocarriers play a crucial role in the treatment of Alzheimer’s disease

Blood Brain Barrier (BBB)

• Highly selective semipermeable border, restricting the transfer of substances between the circulatory system and the central nervous system
• Protects the brain from harmful substances in the blood
• Restricts the passage of pathogens, diffusion of solutes, and large or hydrophilic molecules
• Allows the diffusion of hydrophobic molecules like O2, CO2, and hormones
• Enables the active transport of metabolic products like glucose across the barrier using specific transport proteins
• Presents a challenge for treating malignant brain tumors due to its impermeability

Glioblastoma

• Most common type of brain malignancy
• Most aggressive form of glioma
• Despite combined treatments of surgery, radiation, and chemotherapy, the overall survival rate remains low
• 5-year survival rate of nearly 32% for malignant brain tumors, decreasing to 5% for glioblastoma
• BBB remains impermeable to nearly all large macromolecules and excludes nearly 98% of small-molecule drugs from the brain

Enhancing Drug Delivery to the Brain

• Several technologies have been developed to circumvent the BBB, with nanoparticles emerging as a promising tool
• Nanoparticles' properties like size, shape, chemical composition, surface charge, and conjugation with molecules like glucose, transferrin, insulin, polyethylene glycol, peptides, and aptamers, facilitate BBB penetration

Properties of Nanoparticles

Size and Charge of NPs

• Nanoparticles are small molecules ranging in size from 1 to 1000 nm
• Smaller size is advantageous for crossing the BBB, with increased permeability as size decreases

Ligands and Functional Groups

• NP surfaces can be conjugated with ligands including peptides, proteins, antibodies, and surfactants, enhancing BBB crossing by improving circulation time or binding to endothelial receptors

Glucose

• Conjugation of NPs with glucose enhances BBB penetration by leveraging their binding affinity to specific glucose transporters
• Primarily the GLUT1 subtype responsible for glucose uptake is expressed in the brain endothelium
• Glucose-coated gold nanoparticles are transferred three times faster in cerebral endothelial cell lines compared to non-brain endothelial cell lines

Transferrin

• Transferrin is an iron transporter abundant in the BBB endothelium, facilitating targeted drug delivery to the brain
• NPs conjugated with transferrin receptor (TfR)-targeting ligands or antibodies promote transcytosis
• PEGylated albumin NPs with anchored transferrin have shown increased uptake and localization in the brains of healthy rats when intravenously administered
• Gold NPs with transferrin conjugation enhanced brain localization when systemically administered to BALB/c mice

Insulin

• Insulin-coated gold NPs (INS-GNPs) are found in mouse brains at five times greater concentrations than control untargeted GNPs

Peptides

• Conjugating peptides with NPs allows binding to receptors expressed on BBB endothelial cells, facilitating BBB penetration
• RGD peptide targeting αvβ3-integrin, highly expressed on tumor tissues, is commonly used

Recent Advancements

• BBB is disrupted in conditions like strokes, seizures, multiple sclerosis, AIDS, diabetes, glioma, Alzheimer’s disease, and Parkinson’s disease
• Remodeling of the protein complex in intra-endothelial junctions is an important cause of BBB breakdown

Drug Delivery System (DDS)

• Nanocarrier-assisted intranasal drug carriage system is widely used for brain disease treatment
• Drugs poorly distributed to the brain can be loaded into a nanocarrier-based system
• Nanocarriers interact with endothelial microvessel cells at the BBB and nasal mucosa, increasing drug absorption
• Olfactory nerve fibers stimulate straight nose-to-brain delivery
• Greater drug absorption in brain parenchyma through the secondary nose-to-blood-to-brain pathway

Strategies for Drug Delivery

• Viral vectors
• Nanoparticles
• Exosomes
• Brain permeability enhancers
• Delivery through active transporters in the BBB
• Alteration of administration route
• Nanoparticles for the brain
• Imaging/diagnostics under diseased conditions

Types of Nanoparticles

• Solid lipid nanoparticles (SLNs)
• Liposomes
• Nanostructured lipid carriers (NLC)
• Fullerenes
• Nanoshells
• Quantum dots (QD)
• Super paramagnetic nanoparticles

Polymeric Nanoparticles

• Solid particles composed of macromolecular polymers, ranging in size from 10 to 1000 nm
• Protect encapsulated macromolecules from enzymatic degradation and change the dynamic behavior and tissue distribution of the encapsulated drugs
• Colloidal systems made up of natural or synthetic polymers
• First demonstrated by Langer and Folkman for controlled release of macromolecules, leading to anti-angiogenic drug delivery systems for cancer therapy

Non-Biodegradable Polymers

• Poly(methyl methacrylate) (PMMA)
• Polyacrylamide
• Polystyrene
• Polyacrylates
• Rapid and efficient clearance, but associated with chronic toxicity and inflammatory reactions

Advantages of Polymer Nanoparticles

• Low toxicity
• Good biocompatibility
• Biodegradation at specific sites

Biodegradable Polymers

• Poly(D,l-lactide) (PLA)
• Poly(D,L-glycolide) (PLG)
• Co-polymer poly(lactide-co-glycolide) (PLGA)
• Polyalkylcyanoacrylates
• Poly-Ɛ-caprolactone
• Considered safe and approved by the FDA and EMA for pharmaceutical applications

Non-Synthetic Biodegradable Polymers

• Chitosan
• Alginate
• Gelatin
• Zein
• Albumin

Physico-Chemical Properties

Drug Delivery

• The drug can be dissolved, entrapped, encapsulated, or attached to a nanoparticles matrix

• Nanoparticles, nanospheres, or nanocapsules can be obtained depending on the preparation method

• Nanocapsules confine the drug within a cavity surrounded by a polymer membrane

• Nanospheres physically disperse the drug uniformly

• Biodegradable polymeric nanoparticles coated with hydrophilic polymers like PEG are used as potential drug delivery devices

• Prolonged circulation, organ targeting, DNA carrier in gene therapy, and delivery of proteins, peptides, and genes

• Biomaterials offer extensive chemical diversity for nanoparticle modification

• Large surface area presents opportunities to place functional groups on the surface

Explore the fascinating world of nanotechnology, a branch of science that focuses on structures ranging from 1 to 100 nanometers. This quiz covers its history, key developments, and applications in fields such as medicine and engineering. Test your knowledge and discover the innovative potential of nanoparticles.