Nanoparticles

NPs are a type of

colloidal drug delivery system

NP size

10-100 nm

NA consist of the

drug entity and the polymer/lipids that assemble them into nano sized particles

Major types of nanoparticles

liposomes and micelles

Liposomes

bilayered assemblies

Micelles

aggregates of amphiphilic

Amphilic

can interact with aqueous and lipophilic components

What is the key advantage of micelles and liposomes as applied to drug solubility

increases the amount of drug loading and it increases overall drug solubility carriers

Types of nanoparticles and their general characteristics

1.NPs are not rapidly cleared via the kidneys

2.NPs circulate longer,accumulate better in tumors

3.NPs are internalized by cells via endocytosis

8 characteristics that make nanoparticles useful for anticancer drug delivery:

1.NPs have greater drug loading capacity (increase drug delivered to the tumor)

2.NPs can allow loading of multiple drug molecules, drug-drug combinations

3.NPs allow to modify/tune drug release rate

4.NPs circulate longer, lesser elmination by the kidneys

5.NPs can be modified with PEG; PEG can decrease non-specific uptake into the liver and spleen and increase circulation times

6.Multivalency/Drug targeting

7.Enhanced Permeability and Retention effect for anti-cancer drug delivery

8.NPs can overcome drug resistance and still deliver drug to cells

PEG

-PEGylated particles will not be rapidly cleared via the liver

-opinson:serum albumin

-Pegylated particles will circulates for a longer time in the blood

-PEG reduces opsonion association with NP

Multivalency and Nanoparticle target binding

-NPs can be internalized into cancer cells at higher amounts compared to be free drug

-iron is the ligand that binds the transferrin receptors

-Multivalency refers to the NP surface modification using multiple copies of the targeting ligand

-Ex of receptors over expressed on cancer cells

transferrin and epidermial growth factor receptor

EPR

-NPs owing their nanosize extravstate/permeate into leaky capillaries (made up of endothelial cells) and accumulate in greater amounts in tumors

-The NPs also are retained longer owing to the reduced lymphatic drainage in tumors

Nanoparticles can overcome surface efflux pump mediated drug resistance

-based on the rapid elimination of free drug that enters the cell

-NPs enter cell via endocytosis and avoid recognition by efflux pumps

increase clearance

decrease time drugs stays in the body

t ½ increases

the longer the drug stays in the body

What does PEG modification to the NPs do?

-decreases liver clearance of NPs

-increases circulation times

t 1/2

circulation half-life time (time taken for the original does/concentration to reduce to 50%)

Clearance

volume of blood/plasma cleared of the drug per unit

2 take home messages

-NPs circulate longer this increases half life

-NPs clear slower compared to the free drug

What increase the circulation half-life of liposomes

PEG chains

Dauonoxone

treat leukamia

Ambisome

fugal infection

In summary

-Micelles circulate and have a slower clearance

-Improved therapeutic efficacy compared to the free drug