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Renin Angiotensin Mechanism.

Introduction to Pulmonary Routes of Drug Delivery.

 

Introduction.

  • To treat both local and systemic lung diseases, pulmonary drug delivery (PDD) systems have recently been introduced in the pharmaceutical industry. 

  • It is well known that PDD systems can easily deliver the drug directly to the desired site in the body or to other remote sites through the bloodstream. 

  • The lungs provide a huge surface area of alveoli with a rich capillary network, which acts as an excellent absorbing surface for administration of drugs.

  •  The pulmonary delivery system has been successful in treating asthma and chronic obstructive pulmonary disease (COPD) symptoms over the past few years due to its quick onset of action and higher efficiency. 

  • The new approaches based on interdisciplinary methods like polymer science, pharmaceutical technology, bioconjugate chemistry, and molecular biology are frequently referred to as novel/advanced drug delivery systems. 

  • To reduce drug loss and degradation, avoid negative side effects, and boost bioavailability, a variety of drug delivery and drug targeting systems are already in use or being developed. 

  • New developments in drug delivery techniques are reducing unwanted side effects and increasing the effectiveness of treatments.

  • The respiratory epithelial cells have a prominent role in the regulation of airway tone and the production of airway lining fluid. 

  • Due to the high permeability, large absorptive surface area, and good blood supply of the lungs, the pulmonary route has become a non-invasive administration for the systemic and local delivery of therapeutic agents.

Advantages:

  1. Pulmonary drug delivery has very negligible side effects since the rest of the body is not exposed to drugs.

  2. Onset of action is very quick with pulmonary drug delivery.

  3. First pass metabolism is avoided.

  4. The ability to nebulize viscous drug formulations for pulmonary delivery, thereby overcoming drug solubility issues with the ability to use lipid, water or lipid/water emulsions as drug carriers.

  5. Increased drug delivery efficacy due to size-stable aerosol droplets with reduced hygroscopic growth and evaporative shrinkage.

  6. Liposomal drug formulations remain stable, when nebulized.

  7. Ability to nebulize protein-containing solutions.

  8. Inhaled drug delivery puts drugs where it is needed. 

Limitations:

  1. The oropharyngeal settlement of the formulation may give local adverse effects. 

  2. Patient education is needed to use the delivery devices correctly. 

  3. Effect reproducibility is difficult.

  4. For the systemic delivery of drugs with a small therapeutic index, deviations may be undesirable. 

  5. Drug absorption may be affected due to the mucus and the drug–mucus interactions. 

  6. Drug retention in the lungs is reduced by mucociliary clearance, which may reduce the pharmacological potency of slowly absorbed drugs. 

  7. Targeted drug delivery requires sophisticated delivery devices because the lungs are a difficult surface to reach.

Mechanisms of Respiratory Deposition: 

  • There are three main mechanisms involved in the deposition of inhaled aerosol particles in the respiratory tract: 

    • inertia impaction, 

    • Brownian diffusion and 

    • gravitational settling.

  •  A theory has been developed to predict particle deposition and distribution in the human respiratory system under any breathing situation.

  1. The particle may deposit in various areas of the respiratory tract after passing through the mouth or nose to enter the respiratory tract. The nasal/mouth, pharynx, larynx, and airway bifurcations all experience multiple changes in the direction of airflow while breathing. 

  2. In these areas, larger particles (>0.5 m) may deposit by impaction because they are unable to follow the air streamline. In actuality, a significant portion of the dose emitted by pMDI and DPI devices continues to be deposited by impaction in the oro-pharyngeal region. 

  3. The primary method by which inhaled particles are deposited in the small airways and alveolar region is by sedimentation. 

  4. Small particles (<0.2 μm) may be deposited by diffusion in all regions of the respiratory tract. For nanoparticles smaller than 100 nm, diffusion deposition is crucial. 

  5. For elongated particles like fibrous aerosols, interception deposition is crucial when the long particle dimension is similar to the pulmonary airway dimension.

Commonly Asked Questions.

  1. Give advantages and limitations of the Pulmonary drug delivery system.

  2. Describe different mechanisms of the drug deposition via pulmonary drug delivery system.
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