Podcast
Questions and Answers
Which of the following is NOT a challenge associated with pulmonary delivery of proteins and peptides?
Which of the following is NOT a challenge associated with pulmonary delivery of proteins and peptides?
What is the main advantage of nasal delivery for protein-based drugs compared to oral administration?
What is the main advantage of nasal delivery for protein-based drugs compared to oral administration?
Which of these devices is NOT commonly used for pulmonary delivery of proteins and peptides?
Which of these devices is NOT commonly used for pulmonary delivery of proteins and peptides?
What is the primary reason why a previously developed insulin for pulmonary delivery failed?
What is the primary reason why a previously developed insulin for pulmonary delivery failed?
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Which of the following statements best describes the reason why dry powder inhalers (DPI) are generally used for pulmonary drug delivery?
Which of the following statements best describes the reason why dry powder inhalers (DPI) are generally used for pulmonary drug delivery?
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What is the main factor that determines the effectiveness of drug deposition and distribution in the lungs during aerosol inhalation?
What is the main factor that determines the effectiveness of drug deposition and distribution in the lungs during aerosol inhalation?
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Why is it particularly challenging to deliver drugs to the alveoli in the lungs?
Why is it particularly challenging to deliver drugs to the alveoli in the lungs?
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Which of the following is a common characteristic of protein-based drugs that are suitable for pulmonary delivery?
Which of the following is a common characteristic of protein-based drugs that are suitable for pulmonary delivery?
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What is the primary reason why oral delivery of proteins and peptides is often ineffective?
What is the primary reason why oral delivery of proteins and peptides is often ineffective?
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What is the primary function of microvilli in the nasal cavity in the context of drug delivery?
What is the primary function of microvilli in the nasal cavity in the context of drug delivery?
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Study Notes
Oral Administration Challenges
- Biotech drugs can be inactivated by stomach acids as they are acid labile and degrade at low pH.
- Digestive proteases (pepsin, trypsin, chymotrypsin) commonly degrade proteins during digestion.
- Large size and hydrophilic nature of biopharmaceuticals hinder absorption through intestinal mucosa.
- First-pass metabolism occurs whereby absorbed molecules are metabolized in the liver before entering systemic circulation.
Strategies for Overcoming Oral Challenges
- Encapsulation within an enteric coating protects drugs from stomach environment.
- Inclusion of protease inhibitors (e.g., aprotinin) to prevent protein degradation.
- Use of permeation enhancers to facilitate absorption through gastrointestinal lining.
- Development of mucoadhesive delivery systems to improve interaction with intestinal mucosa is still experimental.
Future Directions in Drug Delivery
- Potential for buccal mucoadhesive systems targeted for vaccines, peptides, and proteins.
- Research and trials in these areas may have faced interruptions.
Pulmonary Delivery Advantages
- Absorption in lungs is inversely related to molecular weight, maximizing bioavailability.
- The alveoli offer over 100 m² of absorption surface, allowing direct entry into the bloodstream.
- High vascularization in lungs prevents structural alteration of proteins and avoids first-pass metabolism.
Delivery Mechanisms in Pulmonary Administration
- Intratracheal instillation is experimental, assessing protein stability and systemic absorption.
- Aerosol inhalation utilizes two-phase colloidal systems; particle size is crucial for effective lung deposition.
- Metered dose inhalers (MDIs) are portable and convenient for users, while nebulizers are non-portable and time-consuming.
- Dry powder inhalers (DPIs) require rapid inhalation for effective aerosolization, posing challenges for pediatric use.
Obstacles in Pulmonary Drug Delivery
- Only a small fraction (approximately 10%) of delivered drugs reach the alveoli; the majority gets retained in the mouth or trachea.
- Agglomeration of aerosol particles reduces efficiency in drug delivery.
- Previous attempts, such as insulin for inhalation, faced challenges leading to market withdrawal.
Nasal Delivery Route Benefits
- Nasal administration is easily accessible with high-density blood vessel network enhancing absorption.
- Nasal microvilli increase the surface area available for drug absorption.
- Nasal delivery avoids first-pass metabolism, allowing direct entry into the bloodstream.
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Description
This quiz explores the difficulties of oral administration of biotech drugs, including inactivation by stomach acids and digestive enzymes, and the challenges of passage through the intestinal mucosa.
