Advanced Drug Delivery (PM3PY2)

Advanced Drug Delivery (PM3PY2) - Study Notes

• Course Information:
  • Module: PM3PY2
  • Lecturer: Prof Francesca Greco
  • Email: [email protected]
  • Office: Chemistry building 1.15
  • Course content focuses on advanced drug delivery and drug targeting, including lectures, a workshop, and final exam assessment.

Lecture Outline

• Lectures: Six lectures covering advanced drug delivery and drug targeting.
• Workshop: Two-hour workshop on advanced drug delivery.
• Assessment: Exam included in the PM3PY2 final exam.

References

• Required Textbooks:

  • Drug Delivery and Targeting (Hillery, Lloyd & Swarbrick), published by Taylor and Francis
  • FASTtrack: Pharmaceutics - Drug Delivery and Targeting (Perrie & Rades), published by Pharmaceutical Press
  • Martin's Physical Pharmacy and Pharmaceutical Sciences, Chapter 22: Drug delivery systems
  • Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, Chapter 20: Novel Dosage Forms and Drug Delivery Technologies

• Additional Textbooks:

  • Engineering Polymer Systems for Improved Drug Delivery (Bader & Putnam), 2014, Wiley
  • Fundamentals of Pharmaceutical Nanoscience (Uchegbu, Schätzlein, Cheng & Lalatsa), 2014 (Springer, new edition coming 2024)

Learning Objectives (Lecture 1)

• Understand drug delivery and drug targeting concepts.
• Learn relevant terminology for drug delivery.
• Understand different drug delivery approaches, including monoclonal antibodies and prodrugs.

Drug Delivery/Targeting Definition

• The goal is to deliver a drug to the correct location in the body at the right time and concentration. Simply being pharmacologically active isn't enough, the drug needs to be at the right place.

Terminology for Drug Delivery / Drug Targeting

• Modified Release: A comparison to conventional release strategies.
• Conventional Dosage Forms: Drug release and plasma levels are based on the physicochemical properties of the active ingredient.
• Non-Conventional Dosage Forms: Drug release and plasma levels are based on the technological characteristics of the formulation.

Drug Release Aspects

• Rate: Examples include very fast release and sustained release.
• Time: Release starts at a certain time after administration.
• Space: Release happens in specific areas or tissues (targeting).

Why Targeting is Important

• Targeting Bacterial Infections: Differences exist between bacterial and mammalian cells.
• Targeting Cancer: Understanding the differences between cancer and healthy cells is critical for effective targeting; the differences are significant and difficult to overcome.

Selective Target Concept

• Magic Bullet: A potent and selective active ingredient, pioneered by Paul Ehrlich (Nobel Prize 1908).

Ordering of Targeting Mechanisms

• 1st Order Targeting: Organ or tissue targeting (e.g., liver targeting).
• 2nd Order Targeting: Specific cell targeting (e.g., tumor cells).
• 3rd Order Targeting: Intracellular compartment targeting (e.g., lysosomes).

Approaches to Targeting

• Magic Bullet: A potent and selective active ingredient.
• Prodrugs: Inactive prodrug is activated at the target site.
• Macromolecular Carrier: A carrier delivers the drug to the desired location.

Monoclonal Antibodies (Magic Bullet Approach)

• General Structure: Antibodies have specific structures.
• Polyclonal Antibodies: Target various antigens.
• Monoclonal Antibodies: Target a single antigen.
• Timeline: Developed in 1975.
• Commercial Applications: Diagnosis (e.g., RIA, ELISA) and treatment (e.g., immunosuppressants, anticancer agents).
• Examples: OKT3 (for preventing kidney transplant rejection), Trastuzumab (Herceptin®) for HER-2 positive breast carcinoma.
• Imaging Agents: Conjugated with diagnostic imaging agents to pinpoint cancer cells. Examples include oncoscint (colon/ovarian) and prostascint (prostate).

Prodrugs

• Definition: Chemically and pharmacologically inactive derivatives of a drug that undergo activation at the target site.
• Reasons for Use: Improved membrane permeability, site-specific administration, increased duration of action, and reduced toxicity/side effects.

Macromolecular Carriers

• Characteristics: Biologically inert macromolecules (usually polymers).
• Types: Particulate and soluble macromolecular carriers.
• Drug Delivery Methods: Drug can be entrapped in the carrier or covalently conjugated.
• Types of Targeting: -Active targeting: Carrier is guided to a specific target through a specific interaction mechanism. -Passive targeting: Exploits the natural distribution pattern. -Physical targeting: Drug carrier is physically guided to the target site.

Technologies Used in Drug Delivery/Targeting

• Polymeric Matrices: Controlled drug release.
• Monoclonal Antibodies/Antibody-Drug Conjugates: Targeting.
• Prodrugs: Site-specific activation.
• Liposomes, Microparticles and Nanoparticles: Drug carriers.
• Micelles: Drug carriers and drug-polymer conjugates

Sizes of Delivery Systems and Devices

• Categorized into Molecular (e.g., monoclonal antibodies), Nano (e.g., nanoparticles), Micro (e.g., microparticles), and Macro (e.g., implantable devices, vaginal rings).

This quiz focuses on the key concepts of advanced drug delivery and drug targeting as covered in the PM3PY2 module. Students will review lecture materials, workshop insights, and reference textbooks to prepare for the final exam assessment. Understanding these principles is essential for anyone pursuing a career in pharmaceutical sciences.