Nanomedicine Overview

Nanomedicine Overview

• Nanomedicine is a rapidly developing field focused on using nanoparticles for drug delivery, diagnosis, and therapy.
• Nanomedicine has the potential to revolutionize personalized medicine and improve drug therapy.

Learning Objectives

• Understanding the basics of nanomedicine and its potential applications in drug delivery.
• Describing the differences between different types of nanoparticle-based drug delivery systems.
• Explaining the advantages and disadvantages of different types of nanoparticle-based drug delivery systems.
• Understanding the factors to consider when choosing nanotechnology for drug delivery.
• Discussing the potential of nanomedicine for personalized medicine and the future of drug.

Medicinal Chemistry

• Physicochemical properties of drugs (FG, acidity/basicity, salt and solubility, chirality) are crucial in drug design.
• Drug target interactions (enzyme/receptor) are important factors in understanding drug mechanism.
• Drug discovery development and optimization (SAR, bioisosterism, rigidification)

Nanoparticle Characteristics

• Nanoparticles are smaller than traditional drugs.
• Nanoparticles have distinctive physical and chemical properties compared to small molecule drugs.
• Examples of nanoparticles include micelles, liposomes, dendrimers, gold nanoshells, quantum dots, and polymers.

Advantages of Nanoparticles

• High surface area-to-volume ratio for loading multiple drugs.
• Improved drug accumulation at pathological tissues using targeting molecules (active targeting).
• Enhanced permeability and retention (EPR) effect for passive targeting mechanism.
• Increased water solubility of poorly water-soluble drugs for enhanced biocompatibility.
• Multifunctional features to differentiate pathological tissue from normal tissue.
• Contribution to personalized medicine.

Nanocarrier Size & Types

• Nanocarriers vary in size, with different types of nanocarriers having specific size ranges.
• Examples of nanocarriers, including liposomes, solid lipid nanoparticles, polymer vesicles, and polymer nanoparticles, are listed.

Nanomedicine Applications

• Using nanoparticles to improve solubility and stability of poorly water-soluble drugs.
• Nanoparticles acting as radiosensitizers to attenuate high-energy X-rays, thereby destroying pathological tissues.
• Utilizing nanoparticles to deliver drugs to specific cells or organs (nanocarriers).
• Theranostic nanoparticles for combining treatment and monitoring of treatment effectiveness.

Liposomes

• Composed of phospholipid bilayers, similar to biological membranes.
• Encapsulate hydrophobic and hydrophilic drugs.
• Vary in size from 20nm to 1µm.
• Good biocompatibility and promote drug diffusion across the plasma membrane.
• Carry hydrophilic and hydrophobic drugs.
• Advantages are easy modification and targeting potential, ability to carry hydrophobic or hydrophilic drugs, and cost-effectiveness.
• Disadvantages include reduced bioavailability, limited high drug loading for hydrophobic drugs, and fast clearance from the blood stream.

Different Types of Liposomes

• Different generations of liposomes utilize varying technologies for enhanced functionality and drug loading.
• Some liposomes have stimuli responsive components to activate the release of the drug in specific environments.

Drug Loading on Liposomes

• Drug loading can occur through various mechanisms, such as mixing drugs and lipids, performing the encapsulation during liposome formation.
• Remote loading uses pH and electrical potential differences to control drug loading.

Solid-Lipid Nanoparticles (SLNs)

• Colloidal carriers consisting of solid lipids at room temperature, dispersed in water or aqueous solution, containing surfactants.
• Biocompatible substances like triglycerides, fatty acids, and steroids, prepare SLN systems.
• Can be oraly administered, and available in different dosage forms.
• Advantages of high drug loading capacity, stability of pharmaceuticals, easy manufacturing, and long-term stability.
• They can encapsulate antitumor drugs and enhance drug solubility.

Nanostructured Lipid Carriers (NLCs)

• Solid matrix at room temperature.
• Enhanced bioavailability, superior formulation properties, and increased drug loading.

Nanoemulsions

• Dispersed system with droplets less than 100nm.
• Unique properties of small-sized droplets with high surface areas.
• Three types: O/W, W/O, and bi-continuous/multiple emulsion (W/O/W and O/W/O).

Examples of Nanoemulsions

• Commercially available nanoemulsions include Abraxane (paclitaxel) and Diprivan (propofol).

Polymer Micelles

• Nanoparticles belonging to the nano colloid class formed by self-assembly of amphiphilic block copolymers in aqueous solution.
• Hydrophobic drugs are encapsulated in the hydrophobic core, and the hydrophilic shell maintains particle stability.

Polymer Vesicles

• Vesicle membranes composed of special amphiphilic block copolymers, similar to natural phospholipids.
• Hydrophobic segments of copolymers reduce contact with water, while hydrophilic domains are projected outwards.
• Hydrophilic groups are distributed on the outer side of the membrane, typical of a bi-layer structure.
• Encapsulation of hydrophobic substances and sub-encapsulation of hydrophilic groups in the water based core.

Dendrimers

• Highly branched polymer molecules.
• Consist of a core (unit) and branches connected around the core.
• Size ranges from 5-20 nm.
• Advantages include high stability, ease of size control, and ease of surface functionalization.
• Multiple sites for binding multiple drugs or targeting multiple drugs or targets

Lipid-Polymer Hybrid Nanoparticles (LPHNs)

• Multilayered particles with lipid and polymeric layers.
• Exhibit high biocompatibility, loading efficiency, and stability.
• Inner layers weakly bound by van der Waals forces.

Multitherapy Nanoparticles

• Contain two or more therapeutics to effectively treat diseases.
• Example is Vyxeos, containing cytarabine and daunorubicin.

Factors to Consider When Choosing Nanotechnology for Drug Delivery

• Macromolecule loading efficiency must be considered given any potential issues with protein instability.
• Production conditions should be mild to prevent protein instability.
• Final properties of the nanosystems must be considered.
• Liposomes, polymeric NPs, and nanostructured lipid carriers are widely used due to their potential for specific targeting.

Enhanced Permeability and Retention (EPR) Effect

• The driving force for nanocarrier delivery to tumor tissues.
• Utilizes the passive mechanisms of EPR, which is a parameter crucial in nanocarrier design.
• Pore size in endothelial walls determines nanoparticle entry.

Nanoparticles for Active Targeting

• Active targeting involves using ligands to bind to specific receptors on tumor cells, for enhanced delivery to tumor cells.
• Useful in precision medicine.

Controlled Release of Drugs from Nanoparticles

• Methods for controlled drug release from nanoparticles.
• Including diffusion-controlled, solvent-controlled.
• Polymer degradation, hydrolytic cleavage.
• Stimuli-sensitive destruction of diffusion barrier.

Challenges of Using Nanoparticles

• Lack of specific regulations for multi-step synthesis and production.
• Lack of standard purification methods.
• Difficulty in large-scale production.
• High cost of production.
• Potential toxicity and immunogenicity.
• More efforts to approve and regulate nano-formulations for FDA and EMA approval.
• High product price.

Safety, Biodistribution, and Stability of Nanocarriers

• Concerns of toxic effects and DNA damage; penetration of viable epidermal cells.
• Biodistribution in unintended organs leading to toxicity, issues with liver metabolism, and limitations to renal elimination.
• Some nanocarriers are efficient and safe to use in food or medicine.

Toxic Effects of Nanoparticles

• Hypersensitivity reactions associated with Alzheimer's disease and high magnetite concentrations.
• Exposure to diesel exhaust (NP) can increase systolic blood pressure, vasodilation, and oxidative stress.
• Chronic exposure to silver causes severe DNA damage.

Take Home Message

• Nanoparticle-based drug delivery systems offer advantages over small-molecule drugs.
• Different types of nanoparticles have different advantages and disadvantages including liposomes, solid-lipid nanoparticles, nanoemulsions, polymeric nanoparticles, dendrimers, lipid-polymer hybrid nanoparticles.
• Multitherapy nanoparticles treat diseases by combining two or more therapeutics.