Nanoparticle Drug Delivery

Group members:

• Adrian A. Pinto• Tejas Pitale• Hooman Mirali• Benjamin A Corbett-Jones• Faizan Arif

Nanoparticle Drug Delivery – Methods of drug

delivery

Nanoparticle Drug Delivery – Nanoparticles

25,000 publication with the keyword nanoparticle in drug

delivery

Spherical Nanoparticles are the simplest drug carriers

Benefits:

Small size

Sequestration - lower and slower

Good transportation

Lower cytotoxicity

Nanoparticle Drug Delivery – Nanotubes

Carbon nanotubes, cyclic peptide nanotubes and template-synthesized nanotubes

Can be manufactured by cylindrical pores of a solid surface

Properties:

Act like a nanoneedle

Multiple drugs can be loaded unto them simultaneously; other functions can be added

High purity

Biocompatible

Insoluble

Chance to be opsonized can be altered by changing their size and active agents on their

outer surface

Nanoparticle Drug Delivery – Nanocapsules

Carrying, targeting and controlling the release of drugs.

Made of a core with a shell

Core: Solid, liquid or gas; base- aqueous solution or oil

Shell: Encapsulates the core

Eg: Biodegradable polymeric nanocapsules and Vault

Sensitive to PH and temperature

Synthesis: putting them in an aqueous environment and the amphiphilic

copolymers will rearrange themselves into core shell structure

Can be used in diabetic patients for intragastric administration of insulin

Nanoparticle Drug Delivery – Nanocrystalline drugs

40% of drugs have low solubility[1].

Nanocrystal drugs- increase solubility and

dissolution rate.

These can be used in common dosage forms like

tablets, inhalation devices, capsules and injections[2].

[1] Keck C M and Müller R H, Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation (2006)[2] Rosen H and Abribat T , The rise and rise of drug delivery(2005)

Nanoparticle Drug Delivery – Nanogels

Nano-scale hydrogels

• Straightforward synthesis; can be synthesized without the presence of the drug

• High drug-loading capacity• Prevent payload aggregation.

Hydrophilic and swell in the presence of water

Respond to

• Ionic strength,• pH • Temperature

Nanomaterial Drug Delivery – Dendrimers

Similar to snow crystals

and lightning

Strong structural control

Biocompatible

Water soluble

Improve drug properties

Prolonged plasma circulation time

Helps in Boron Neutron Capture therapy

Source: [3] Starpharma, How are Dendrimers made

[3] Starpharma, How are Dendrimers made, http://www.starpharma.com/technology/how_are_dendrimers_made_

Nanomaterial Drug Delivery - Liposomes

Artificial vesicles developed from amphiphilic phospholipids

Treatment of various illnesses

Table 1. Different uses of Liposomes in treatment of illnesses

Brand Drug Treatment of

AmBisome Amphotercin B Fungal Infections

Doxil, Caelx DoxorubicinOvarian cancer, Kaposi’s

sarcoma and breast cancer

Depocyt Cytarabine Lymphomatous meningitis

Daunoxome Daunorubicine Kaposi’s sarcoma

Nanoparticle Drug Delivery – Polymeric Micelles

Hydrophilic shell

Hydrophobic Core

Drug Payload

Artificial cell like structures similar to natural carriers

Core/shell structure with hydrophobic core and

hydrophilic shell

Suitable use for drugs that have poor aqueous

solubility

Generally made up of block copolymers

well suited in treating cancer

Nanoparticle Drug Delivery – Nucleic Acid

macromolecules made from monomers known as nucleotides

building material to create nanostructures

Two methods have been devised to create rigid structures

DNA origami Nanocages (tensegrity principle))

DNA box with a lid that is controlled by the environment for use in drug delivery

Nanoparticle Drug Delivery – Polymeric drug conjugates Type of targeted Nano drug delivery system

Drug is connected to a bio degradable polymer

with conjugate covalent bonds.

Fig. 1 Schematic presentation for (a) polymeric prodrug with

targeting agent and (b) hyperbranched polymer conjugate with

targeting and imaging agent.

Jayant Khandare , Tamara Minko; Progress in Polymer Science Polymer–drug conjugates: Progress in polymeric prodrugs;,

Volume 31, Issue 4, 2006, 359 - 397

Nanoparticle Drug Delivery – Advantages

Advantages of Polymeric Drug Conjugates

• Improved therapeutic properties of peptides and proteins.

• Prolonged half life in plasma.

• Higher stability during transit.

• High water solubility due to bio degradable polymers

• Accurate tumor targeting.

• Easy administration of drug

Nanoparticle Drug Delivery – Solid Lipid NanoParticles

Sub micron colloidal particles (50-1000 nm)

Physiological lipids dispersed in aqueous solution

with surfactants

Colloidal particles are made of core which is coated

with a mono layer of phospholipid coating

Nanoparticle Drug Delivery – Methods Of Preparation

Nanoparticle Drug Delivery – factors impacting drug delivery

Particle Size

Surface

characteristics

• minute size

• comparative mobility *

• available to a large number of biological targets

• Higher intracellular uptake

• Nanoparticles are attacked by phagocytes

• Surface hydrophobicity

* Ref: Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55: 329-47

Nanoparticle Drug Delivery – Targeting strategies

Passive targeting

Active targeting

• Drug accumulation in tumor tissues

• Gap junctions between lymphatic drainage and endothelial cells

• Dilation of tumor vessels leading to diffusion of molecules

• Higher intracellular uptake

• attachment of affinity ligands with nano-carrier surfaces

• Ligand – receptor interactions

• Binding of target cells by nano-carriers

* Ref: Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55: 329-47

Nanoparticle Drug Delivery – Challenges

Biological

understanding

Safety concern

Manufacturing

• shortage of knowledge

• low targeting efficiency

• Rapid clearance by the immune system

• adverse effects

• nano-materials and biological system interactions

* Ref: Panyam J, Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55: 329-47

• Pilot techniques

• Economic and financial barriers