Lecture 8

Advantages of Pulmonary Drug Delivery

1. Used for local delivery of drugs to the lungs for asthma treatment.

2. Non-invasive route of systemic drug delivery.

3. Rapid absorption and fast onset of action (comparable to IV drug

administration)

4. Avoid harsh conditions of the GIT

5. Drug efflux transporters and metabolizing enzymes are present in

the lung at much lower levels than the gastrointestinal tract

Limitations to Pulmonary Drug Delivery

1. Inhaled drug particles must possess specific particle diameter in

order to pass from nose and mouth filters and at the same time
dispose inside the lung

2. Excipients used in drug formulation can cause irritation or

permanent injury to the lung.

3. High disposition of drug in the oro-pharynx region.

Why are peptides and proteins rapidly absorbed after inhalation

than after subcutaneous injection?

Rapid onset

High rate

High blood supply in alveolus barrier

Alveolus blood barrier is permeable

Very large absorptive surface area

No metabolic (degradative) enzymes

No efflux pumps

Very thin membrane (0.1-0.2 Micrometer)

Presence of protein binding sites

 Factors affecting Pulmonary Drug Delivery

Drug-related factors

Particle diameter:

Drug particle size affects the mechanism of drug disposition into the
lungs:

Drug particles in the range of 0.5-5m: sedimentation

Drug particles> 5m: gravity

Drug particles <0.5m: diffusion (Brownian motion)

Interaction forces:

For drug particles to be flowable and easily dispensed, interaction

forces between drug particles must be overcome during drug particles
preparation steps.

Drug dose

Drug concentration at target site.

Pulmonary Drug Delivery Devices

Pulmonary drug carrier systems

Biodegradable microspheres

Pulmonary administration of aerosolized microspheres allows a sustained

and prolonged release of drugs for respiratory or non respiratory diseases.
Microspheres can be produced following different requirements such as
the morphology, the size and the porosity by varying different
technological parameters during their preparation. Microspheres are less
hygroscopic and are then less liable to swell in the presence of moisture
located into the lungs

Nanotechnology in drug delivery

New drug delivery areas in which nanotechnology efforts are being

focused.

Why nanotechnology is used in poorly water soluble drugs?

1. Improving solubility of poorly water soluble drugs.

Nanotechnology-based solutions to improve drug solubility:

When the particle size of a drug is reduced to the nanometre range,

the surface area is significantly increased, thereby enhancing the
solubility of the drug. Size reduction can occur via a number of
means, including milling or homogenization techniques.

The nanostructuring process creates a porous honeycombed

structure that dramatically increases the carriers surface area. In
this case, the drug molecules are immobilized within the nanosized
pores in the structure, which can be varied to carry a range of
different sized molecules.

Lecture 9

Nanotechnology provides the following solutions to the problems of

drug delivery: (Advantages)

Improving solubilization of the drug.

Using non-invasive routes of administration eliminates the need for

administration of drugs by injection.

Development of novel nanoparticle formulations with improved

stabilities and shelf-lives.

Development of nanoparticles formulations for improved

absorption of insoluble compound and macromolecules enables
improved bioavailability and release rates, potentially reducing the
 amount of dose required and increasing safety through reduced side
effects.

Manufacture of nanoparticle formulations with controlled particle

size, morphology, and surface properties could be more efficient
and less expensive than other technologies.

Nanoparticle formulations that can provide sustained release

profiles up to 24 h can improve patient compliance with drug
regimens.

Direct coupling of drugs to targeting ligands restricts the coupling

capacity to a few drug molecules, but coupling of drug carrier
nanosystems to ligands allows input of thousands of drug
molecules by means of one receptor targeted ligand.

Liposomes

Liposomes are stable vesicles formed by phospholipids and similar

amphiphilic lipids. Liposome property vary with lipid composition, size,
surface charge and the method of preparation.

In a cell, one layer of heads faces outside of the cell, attracted to the water
in the environment. Another layer of heads faces inside the cell, attracted
by the water inside the cell. The hydrocarbon tails of one layer face the
hydrocarbon tails of the other layer, and the combined structure forms a
bilayer.

Lipid bilayer of liposomes are similar in structure to those found in living

cell membranes and can carry lipiphilic substances such as drugs within
these layers. Liposomes can be conjugated to antibodies or ligands to
enhance targeting of specific drug or gene therapy.

The size of these spheres is very small, in the order of a nanometer. They
act as a carrier for the enclosed substances. It is postulated that when they
reach the outside of a living cell membrane they may become accepted
as part of the membrane, being of the same composition.

Advantages of liposomes as drug delivery system

 Liposomes are biocompatible, completely biodegradable, non-
toxic, flexible and non-immunogenic for systemic and non-
systemic administrations.

Suitable for delivery of hydrophobic and hydrophilic drugs and

agents.

Liposomes have the ability to protect their encapsulated drug from

the external environment and to act as sustained release depots
(Propranolol, Cyclosporin).

Flexibility to couple with site-specific ligands to achieve active

targeting (Anticancer and Antimicrobial drugs).

Four kinds of liposomes

Immunoliposomes: are stealth liposomes that have been specially

designed for active targeting to a given type of tissue or organ that
the liposome is able to recognize by its molecular fingerprint. This
is accomplished by highly specific chemical modifications to the
PEG molecules or the lipid bilayer of the liposomes, or both.

Cationic liposomes: are stealth liposomes whose surfaces (both

exterior and interior) are positively charged so as to increase the
loading efficiency of recombinant DNA. These liposomes are used
for gene therapy, in which certain disorders are treated by
introducing specifically engineered genetic material (DNA) into
the patients cells through active targeting.