Drug targeting to particular organs

Drug Targeting to
Particular Organs
Prof. Dr. Basavaraj K. Nanjwade M. Pharm.,
Ph. D
Department of Pharmaceutics
KLE University College of Pharmacy,
BELGAUM-590010, Karnataka, India.
Cell No.: 0091-9742431000
E-mail: nanjwadebk@gmail.com
28 February 2013 1DDSEC, Prince of Songkla University, Hat Yai, Thailand.

CONTENT
• Drug Delivery to respiratory system.
• Problems of drug delivery to the brain
and targeting to brain.
• Drug delivery to Eye.
• Drug targeting in Neoplastic diseases.

Targeting all respiratory
system
• Dosing to the complete respiratory system has
previously only been possible by special
nebulizer.
• Dosing to the complete respiratory system has
only been regarded as an option for a very
narrow range of therapeutics.

Pulmonary dose + Nasal
dose
• Delivery to both nasal and pulmonary
airways, it will be possible to target the
complete airway system.
• Two separate formulation technologies for
reaching nasal airways and for the pulmonary
airways.
• Nasal delivery and pulmonary delivery places
each their requirements on the powder
formulation characteristics.

Targeting Lung Regions
• Extrathoracic and alveolar regions can
effectively be targeted with mono- and
polydisperse aerosols respired steadily.
• Effective targeting of the bronchial region can
only be achieved with bolus inhalations.
• When particles are suspended in a gas heavier
than air, targeting the alveolar region can be
enhanced.
28 February 2013 DDSEC, Prince of Songkla University, Hat Yai, Thailand. 5

Targeting Lung Regions
• Optimization Particle and Breathing
Parameters
• Bolus Inhalation
• Gas Composition

Optimization Particle and
Breathing Parameters
• Targeting extrathoracic, upper bronchial,
lower bronchial, and alveolar region for steady
state breathing of aerosols.
• The targeting efficiency can be increased for
mono-as well as polydisperse aerosols to more
than 90% by combining extrathoracic and
upper bronchial regions and lower bronchial
and alveolar regions.

Monodisperse particles

Mono and Polydisperse
particles

Targeting Combined
regions
28 February 2013
DDSEC, Prince of Songkla University, Hat Yai, Thailand.
10

Bolus Inhalation
• Boluses are very suitable for targeting as long
as the particle sizes and breathing patterns
are used.
• Particles 1 μm in size are ideal for this
purpose because of their very low deposition
on their way to the targeted region and their
large deposition in the small peripheral lung
structures during breath-holding.

Hydrophobic 1µm
particles

Gas Composition
• The particle-loaded inhaled gas is heavier
(lighter) than air, particles penetrate
deeper (less deep) into the lungs.
• Deposition occurs deeper in the lungs when
particle-loaded sulphox rather than particle
loaded heliox is inhaled.

Gas composition

Emerging Carriers for
Respiratory Drug
Delivery
• Nanoparticle Formulations for
Inhalation
• Vaccine delivery
• Gene therapy

Targeted delivery
to the Respiratory System

Liposomes as drug delivery
systems to alveolar
macrophage

Protein and Peptide
Drugs
to the Respiratory System• Improving the transport of the drug to its site
of action
• Improving the stability of the drug in vivo
• Prolonging the residence time of the drug at
its site of action by reducing clearance
• Decreasing the nonspecific delivery of the drug
to non-target tissues

Drugs
to the Respiratory System
• Decreasing irritation caused by the drug
• Decreasing toxicity due to high initial doses of the
drug
• Altering the immunogenicity of the protein
• Improving taste of the product
• Improving shelf life of the product

Drug Targeting

Avoiding injections
Bioavailability without
Promoter
Bioavailability with
Promoter
Nasal 2 5–40
Rectal 3 40
Buccal 0.7 25
Conjunctival 0.3–6.6 40
Pulmonary 8–30 100

Different Types of Targeting

Drug Delivery to
Brain

Problems of Drug Delivery
to the Brain
• The relative impermeability of the BBB
results from tight junctions between capillary
endothelial cells which are formed by cell
adhesion molecules.
• Approximately 98% of the small molecules and
nearly all large molecules (mwN1 kD,
kilodaltons), such as recombinant proteins or
gene-based medicines do not cross the BBB.

Blood Brain Barrier

Drug Targeting to Brain
• To bypass the BBB and to deliver
therapeutics into the brain, three
different approaches are currently used.
1.Invasive approach
2.Pharmacological approach
3.Physiological approach

Drug Targeting in the Brain
Areas

Pharmacological approach
• Pharmacological approach consists of
modifying, through medicinal chemistry, a
molecule that is known to be active against a
CNS target to enable it to penetrate the BBB.
• Modification of drugs through a reduction in
the relative number of polar groups increases
the transfer of a drug across the BBB.
• Lipid carriers have been used for transport.

Transport of molecules
across the BBB

Pharmacological approach
• Formulation of drugs facilitates brain delivery
by increasing the drug solubility and stability
in plasma
• Limitations: The modifications necessary to cross
the BBB often result in loss of the desired
CNS activity. Increasing the lipophilicity of a
molecule to improve transport can also result in
making it a substrate for the efflux pump P-
glycoprotein (P-gp).

Physiological approach
• Physiological approach is recognized by the
scientific community as the onewith the most
likely chance of success.
• Transporter-mediated delivery
• Receptor-mediated transcytosis
• Receptors at the blood–brain barrier

Physiological approach
• Transferrin receptor (TR)
• Insulin receptor
• Liposomes coated with targeting molecules
such as antibodies, Trojan Horses Liposomes
(THL)
• Nanoparticles coated with transferrin or
transferrin receptor antibodies

Motivation

Blood Brain Barrier
Transport Mechanism

Drug Delivery to Eye

Anatomy of the Eye

 Ophthalmic preparation
 Applied topically to the cornea, or instilled in the
space between the eyeball and lower eyelid
 Solution
• Dilutes with tear and wash away through
lachrymal apparatus
• Administer at frequent intervals
 Suspension
• Longer contact time
• Irritation potential due to the particle size of drug
 Ointment
• Longer contact time and greater storage stability
• Producing film over the eye and blurring vision

 Emulsions
• Prolonged release of drug from vehicle but
blurred vision, patient non compliance and
oil entrapment are the drawbacks.
 Gels
• Comfortable, less blurred vision but the
drawbacks are matted eyelids and no rate
control on diffusion.

Controlled delivery system
– Release at a constant rate for a long time
– Enhanced corneal absorption
– Drug with not serious side effect or tolerate
by the patient

Advantages
 Increase ocular residence, hence, improving
bioavailability.
 Possibility of providing a prolonged drug release
and thus a better efficacy.
 Lower incidence of visual and systemic side
effects.
 Increased shelf life with respect to aqueous
solutions.
 Exclusion of preservatives, thus reducing the
risk of sensitivity reactions

 Possibility of targeting internal ocular tissue
through non-corneal routes
 Reduction of systemic side effects and thus
reduced adverse effects.
 Reduction of the number of administration and
thus better patient compliance.
 Administration of an accurate dose in the eye,
which is fully retained at the administration site,
thus a better therapy.
Advantges

Classification
Mucoadhesive dosage forms
Ocular inserts
Collagen shield
Drug presoaked hydrogel type contact lens
Ocular iontophoresis
Polymeric solutions

Ocular penetration enhancers
Phase transition systems
Particulate system like, microspheres and
nanoparticles
Vesicular systems like liposomes, niosomes,
phamacosomes and discosomes
Chemical delivery system for ocular drug
targeting
Classification

Drug targeting to
Neoplastic Diseases

Targeted Delivery to Tumors
• Goal is to inject treatment far from tumor
and have large accumulation in tumor and
minimal accumulation in normal
cells/organs.

Cancer Treatments
• Tumor penetration is a key issue for successful chemotherapy

Nanoparticle use in
Cancer Treatments
• Because of their small size,
nanoparticles can pass through
interstitial spaces between
necrotic and quiescent cells.
• Tumor cells typically have larger
interstitial spaces than healthy
cells
• Particles collect in center bringing
therapeutics to kill the tumor
from inside out.

Nanoparticle Targeting and
Accumulation
• To maximize their effectiveness, the microenvironment
of the tumor must be quantified and vectors developed to
specifically target the tumor.
Necrotic
Quiescent
Proliferating
Therapeutic

Thank YouThank YouE-mail: nanjwadebk@gmail.com
Cell No: 00919742431000

Drug targeting to particular organs

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