Drug targeting to particular organs
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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: [email protected] CONTENT. Drug Delivery to respiratory system.

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Drug Targeting to Particular Organs

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Drug targeting to particular organs

Drug Targeting to Particular Organs

Prof. Dr. Basavaraj K. NanjwadeM. Pharm., Ph. D

Department of Pharmaceutics

KLE University College of Pharmacy,

BELGAUM-590010, Karnataka, India.

Cell No.: 0091-9742431000

E-mail: [email protected]

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Content

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeting all respiratory system

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Pulmonary dose nasal dose

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeting lung regions

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeting lung regions1

Targeting Lung Regions

  • Optimization Particle and Breathing Parameters

  • Bolus Inhalation

  • Gas Composition

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Optimization particle and breathing parameters

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Monodisperse particles

Monodisperse particles

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Mono and polydisperse particles

Mono and Polydisperse particles

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeting combined regions

Targeting Combined regions

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Bolus inhalation

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Hydrophobic 1 m particles

Hydrophobic 1µm particles

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Gas composition

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Gas composition1

Gas composition

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Emerging carriers for respiratory drug delivery

Emerging Carriers for Respiratory Drug Delivery

  • Nanoparticle Formulations for Inhalation

  • Vaccine delivery

  • Gene therapy

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeted delivery to the respiratory system

Targeted delivery to the Respiratory System

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Liposomes as drug delivery systems to alveolar macrophage

Liposomes as drug delivery systems to alveolar macrophage

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Protein and peptide drugs to the respiratory system

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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Protein and peptide drugs to the respiratory system1

Protein and Peptide 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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting

Drug Targeting

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Avoiding injections

Avoiding injections

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Different types of targeting

Different Types of Targeting

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug delivery to brain

Drug Delivery to Brain

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Problems of drug delivery to the 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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Blood brain barrier

Blood Brain Barrier

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting to brain

Drug Targeting to Brain

  • To bypass the BBB and to deliver therapeutics into the brain, three different approaches are currently used.

  • Invasive approach

  • Pharmacological approach

  • Physiological approach

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting in the brain areas

Drug Targeting in the Brain Areas

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Pharmacological approach

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Transport of molecules across the bbb

Transport of molecules across the BBB

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Pharmacological approach1

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).

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Physiological approach

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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Physiological approach1

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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Motivation

Motivation

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Blood brain barrier transport mechanism

Blood Brain Barrier Transport Mechanism

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug delivery to eye

Drug Delivery to Eye

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Anatomy of the eye

Anatomy of the Eye

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug delivery to eye1

Drug Delivery to 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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug delivery to eye2

Drug Delivery to Eye

  • 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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting to particular organs

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

Drug Delivery to Eye

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Advantages

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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Advantges

Advantges

  • 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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Classification

Classification

  • Mucoadhesive dosage forms

  • Ocular inserts

  • Collagen shield

  • Drug presoaked hydrogel type contact lens

  • Ocular iontophoresis

  • Polymeric solutions

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Classification1

Classification

  • 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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug delivery to eye3

Drug Delivery to Eye

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting to neoplastic diseases

Drug targeting to Neoplastic Diseases

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Targeted delivery to tumors

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Cancer treatments

Cancer Treatments

  • Tumor penetration is a key issue for successful chemotherapy

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Nanoparticle use in cancer treatments

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.

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Nanoparticle targeting and accumulation

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

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


Drug targeting to particular organs

Thank You

E-mail: [email protected]

Cell No: 00919742431000

DDSEC, Prince of Songkla University, Hat Yai, Thailand.


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