lec31_Nano delivery systems (II)

Page 1: Introduction

  • Title: Nano-based Drug Delivery Systems (II)

  • Author: Bahaa Mustafa, Ph.D.

  • Course: Pharmaceutics I (PSC171303)

  • Date: 11/05/2024

Page 2: Learning Objectives

  • Describe the preparation procedure of liposomes.

  • Identify different types of liposomes.

  • Understand the properties of stealth liposomes.

  • Explain the application of immunoliposomes in drug delivery.

  • Know the advantages of liposome formulation.

Page 3: Configurations of Liposomes

  • Types of Liposomes:

    • LUV: Large Unilamellar Vesicle

    • SUV: Small Unilamellar Vesicle

    • LMV: Large Multilamellar Vesicle

    • MVV: Multivesicular Vesicle

Page 4: Rotovap Preparation of Liposome (Thin Film Hydration Method)

  • Preparation Steps:

    • Lipids and hydrophobic drugs in organic solvent.

    • Hydrophilic drugs in water solution.

    • Rotary evaporation to form a dry lipid film.

    • Hydration and sonication of the dry film.

    • Centrifugation followed by extrusion.

    • Dialysis, homogenization, and ultrafiltration for purification.

    • Downsizing and final liposome preparation into MLVs, LUVs, or SUVs.

Page 5: Liposome Extruder

  • Extrusion Technique:

    • Liposome suspension passed through membrane filter with defined pore size.

    • Lipid dispersion forced through filters of varying sizes.

    • Results in excellent homogeneity of liposome size distribution.

    • Polycarbonate is commonly used as membrane for extrusion.

Page 6: Quiz Question

  • Question: Which is the correct configuration of the following liposome?

    • A. Small Unilamellar Vesicle (SUV)

    • B. Large Multilamellar Vesicle (LMV)

    • C. Large Unilamellar Vesicle (LUV)

    • D. Multivesicular Vesicle (MVV)

Page 7: Cellular Uptake of Liposomes

  • Mechanisms of Uptake:

    • Fusion with cellular membranes.

    • Surface interactions impacting uptake.

    • Receptor-mediated endocytosis and lipid exchange.

    • Nucleus: endocytosis and pinocytosis.

Page 8: Mononuclear Phagocytic System (MPS)

  • Overview:

    • Part of the immune system, comprising phagocytic cells.

    • Primarily located in the liver, spleen, lungs, and lymph nodes.

    • Rapid clearance of nanoparticles via phagocytosis.

    • Surface Characteristics:

      • Hydrophobic surfaces lead to preferential uptake by liver/spleen.

      • Hydrophilic nanoparticles show minimal uptake.

    • Surface modification with PEG helps reduce uptake by MPS.

Page 9: Different Types of Liposomes

  • Types:

    • Conventional Liposomes: Neutral or negatively charged.

    • Stealth Liposome: Sterically stabilized with polymer coatings for longer circulation.

    • Immunoliposome: Antibody-modified for targeting.

    • Cationic Liposome: Positively charged for nucleic acid delivery.

Page 10: Stealth Liposome

  • Characteristics:

    • Long-circulating liposomes coated with biocompatible polymers (e.g., PEG).

    • Protective layer inhibits recognition by macrophages.

    • Prolonged circulation enhances uptake by target cells.

    • Unmodified liposomes face rapid clearance by MPS.

Page 11: Stealth Liposome Case Study

  • Doxorubicin: A chemotherapy drug.

    • Standard circulation half-life: 20 minutes.

    • Doxil: Pegylated version with 55-hour circulation half-life.

    • Treatment involves one i.v. infusion every 4 weeks; slow drug release from liposomes.

    • Improved tumor targeting and reduced cardiac toxicity.

Page 12: Problems of Liposomes

  • Challenges:

    • High cost of production.

    • Poor long-term stability in presence of water.

    • Low encapsulation efficiency for specific drugs.

    • Difficulties in scaling up production.

Page 13: Liposome Formulations in the Market

  • Advantages:

    • Biocompatibility and ability to encapsulate hydrophilic and hydrophobic drugs.

    • Capacity to reduce drug toxicity while improving therapeutic efficacy.

Page 14: AmBisome - First Approved Liposome Formulation

  • Approval: 1997

  • Molecular Ratio: Drug: Lipid = 1:9; Particle Size: 45-80 nm.

  • Storage: Sterile, freeze-dried form; reconstitution with sterilized water.

  • After reconstitution, store in refrigerator and use within 24 hours.

Page 15: Comparison: Conventional Amphotericin B vs AmBisome

  • Conventional Amphotericin B:

    • Used for systemic fungal infections; various patient groups.

    • Quick distribution; potential for nephrotoxicity.

    • Dose: 0.3 to 1 mg/kg/day.

  • AmBisome:

    • Liposomal form of Amphotericin B with decreased side effects.

    • Prolonged drug exposure; recommended dose: 3-5 mg/kg/day.

Page 16: References

  • Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems, 12th Edition, by Loyd V. Allen, Jr. and Timothy B. McPherson.

  • Khan, A., Majeedullah, & Khan, S.A. (2022). Tablets and Capsules. In: Essentials of Industrial Pharmacy. AAPS Advances in the Pharmaceutical Sciences Series.

  • AULTON, M. E., TAYLOR, K., (2013). Aulton's Pharmaceutics: The Design and Manufacture of Medicines.