Nanotechnology in lung drug delivery

NANOTECHNOLOGY IN LUNG DRUG

DELIVERY

Introduction of drug delivery in lung. Overview the physiology of respiratory system.

Route of administration in lung drug delivery.

Drug delivery for lung cancer. Drug delivery for tuberculosis.

OUTLINE

Delivery drug to the respiratory system is performed for diagnostics and treatment of local disorders.

Respiratory tract may be used to gain systemic absorption (without first-past metabolism).

The main types of dosage form: solutions (for nebulisation) and particles (drug powder or aerosol)

INTRODUCTION

Ensure the required dose of drug is delivery to the site of action minimize the incidence of side effects.

Large surface area of the lung offer the aviable alternative to parenteral medications.

Rapid onset of action following respiratory drug delivery beneficial for the treatment of ashma.

Portable, convenient for the patients to carry.

Advantages

In some dosage forms, coordination is required between activating the inhaler and inspiration. If not, drug may deposits in the upper air way.

Deposition of drug to lower airway may be impeded in presence of high volume of mucus.

The physical stability of pharmaceutical aerosols may be problematic.

Disadvantages

Physiology of the respiratory system.

The role of respiratory tract is in the transfer of oxygen in to the blood from inspired air.

The diffusion barrier between the blood supply and the alveoli is relatively thin, enabling rapid drug diffusion and absorption.

The epithelial cells are ciliated and responsible for the transport tract for subsequent elimination.

Physiology of the respiratory system.

Delivery into lungs for diagnostic purposes.

Oral administration. Inhaled administration: dry powder carriers or suspension.

ROUTE OF ADMINISTRATION

Instilled iodinated nanoparticles (Ketai et al) result in a contrast enhancement.

Magnetic nanoparticles for diagnostics: need more details research to be used as a safe diagnostic tools.

Nanoparticles seem to be promising and powerful tool for imaging purposes of the lung.

DELIVERY INTO LUNGS FOR DIAGNOSTICS PURPOSE

Oral route is convenient for drug administration of conventional dosage form.

Oral delivery of nanoparticles for drug targeting has not shown in the past promising results.

Oral delivery of NPs might not be the proper route of administration to reach the lungs.

ORAL ADMINISTRATION

INTRAVENOUS INJECTION

INHALED ADMINISTRATION

Use for: many classes of drugs and

applications (including anti-tumor therapy, gene therapy, AIDS therapy, radiotherapy)

in the delivery of macromolecules (peptides and proteins or small molecules as antibiotics, virostatics and vaccines)

Advantages:- The dose needed to produce a pharmacological effect can be reduced (cf. oral dosing);- Low concentrations in the systemic circulation are associated with reduced systemic side-effects;- Rapid onset of action; - Avoidance of gastrointestinal upset;- Avoidance of intestinal and hepatic first-pass metabolism.

INHALED ADMINISTRATION

Disadvantages:- Oropharyngeal deposition may give local side-effects;- Patients may have difficulty using the delivery devices correctly.

INHALED ADMINISTRATION

The therapeutic AEROSOL

The dispersed phase may be liquid, solid or a combination of the two.

Atomization is the process by which an aerosol is produced and

can be electrically, pneumatically or mechanically powered.

The therapeutic AEROSOL

Categories: Nubilizer

The therapeutic AEROSOL

Categories: Nubilizer Pressurized metered-dose inhaler

(pMDI);

The therapeutic AEROSOL

Categories: Nubilizer Pressurized metered-dose inhaler

(pMDI); Dry powder inhaler (DPI)

The therapeutic AEROSOL

Delivery of nanoparticles using dry powder carriers

Delivery of nanoparticle suspensions using nebulization

INHALED ADMINISTRATION

Delivery of nanoparticles using dry powder carriers

used “ultrafine” hydrophilic particles ( HPMCP < 100nm) + hydrophobic drug improve the aerosolization properties

mixed the surface modified drug powder dispersion with lactose improve better dispersion in inhalation

spray- or freeze-dried Dry powder

INHALED ADMINISTRATION

Delivery of nanoparticle suspensions using nebulization

Advantage:+ Preventing the aggregation.

Disadvantage:+ The physical and chemical

properties.

INHALED ADMINISTRATION

TOXICITY OF INHALED NANOPARTICLES

Toxicity of inhaled ultrafine particles (UFP; <100 nm

aerodynamic diameter)

Delivery of nanoparticle suspensions using nebulization

diethylaminopropyl amine-poly (vinyl alcohol)-grafted-poly (lactide-co-glycolide) (DEAPA-PVAL-g-PLGA), as well as with increasing amounts of carboxy methyl cellulose. this new polymer has high encapsulation efficiency for drug molecules by utilizing electrostatic interactions.

INHALED ADMINISTRATION

Nanomedicine has the potential to significally change the course of diagnostics and treatment of cancer.

Cancer nanomedicine provides:1. Sensitive cancer detection (early

detection).2. Enhance treatment efficacy.3. Significantly minimize adverse effects

associated with standard therapeutics.

NANOMEDICINE IN LUNG CANCER

Same size scale with biomolecules (receptors, antibodies and nucleic acids): can be functionalized with biomolecules target specific organelles.

Targeting specific cells: NPs can release therapeutic payload at cancer sites

reducing nonspecific toxicity. Detect cancer in very small amount of cells

or tissues.

Advantages of nanomedicine in lung cancer

High surface areas Higher therapeutic payload.

Delivered and recognized by a receptor high-dose therapeutic load released can damage to cancer cells at targeted site

Advantages of nanomedicine in lung cancer

Nanostructures can overcome solubility and stability issues through surface modification/ wrappings or additional formulation.

Nanostructure have novel physical properties, which can be utilized for bioimaging.

Advantages of nanomedicine in lung cancer

PULMONARY DISEASE

Pulmonary tuberculosis (TB)is caused by the bacteria Mycobacterium tuberculosis (M. tuberculosis)

Pulmonary tuberculosis (TB)

PULMONARY TUBERCULOSIS (TB)

SYMPTOMS

-The primary stage of TB does not cause symptoms. When symptoms of pulmonary TB occur, they can include: +Cough (usually with mucus) +Coughing up blood +Excessive sweating, especially at night +Fatigue +Fever +Weight loss

-Other symptoms that can occur: +Breathing difficulty +Chest pain +Wheezing

TREAMENT:

-Commonly used drugs include:

+Isoniazid+Rifampin+Pyrazinamide+Ethambutol

-Other drugs that may be used to treat TB include:

+Amikacin+Ethionamide+Moxifloxacin+Para-aminosalicylic

acid+Streptomycin

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