The development of liposomes as a drug delivery system has fluctuated since its introduction in the late 1960's by A.D. Bangham. While academic research of liposomes as a model membrane system has always flourished, as the exponential growth of papers can testify, the application of these findings to medically useful products has gone through several crises. Following the original optimism in the 70's and early 80's, a period of severe skepticism ensued at the end of the 80's and beginning of the 90's, culminating in a moderate but real optimism in the mid 90's, as a result of a successful launch of the first products in the US and Europe.
In this collection of papers, the editors have gathered the most promising ideas, approaches, applications and commercial developments, thereby presenting an up-to-date compilation of the present status of the field. This includes such broad areas as anti-cancer chemotherapy immune stimulation and infectious diseases. Currently, the major areas of progress are in delivery of anti-fungal agents by conventional liposomes or lipid-based carriers and systemic anticancer therapy using long-circulating liposomes. The future applications as characterized by the direction of present day research is in specific targeting and delivery of informational molecules such as DNA plasmids (genes), antisense oligonucleotides or ribozymes. Other future developments may be in topical delivery, vaccination and in diagnostics.
Features of this book:
• Contributions from almost all the leading labs in the field
• Up-to-date, critical reviews bridged by editors' introductions
• Organized into a logical framework.
Medical Applications of Liposomes, 1st Edition
1. Liposomes in Medicine.
General introduction (D.D. Lasic, D. Papahadjopoulos). Liposome research in drug delivery and targeting: Thoughts of an early participant (G. Gregoriadis). 2. Stimulation of Immune Response and Vaccination.
Class I presentation of liposomal antigens (M. Rao, C.R. Alving). Major histocompatibility complex Class II molecules, liposomes and antigen presentation (L. Leserman, N. Barois). Systemic activation of macrophages by liposomes containing synthetic immunomodulators for treatment of metastatic disease (L. A. Worth et al.
). DNA vaccination: A role for liposomes (G. Gregoriadis et al.
). "Virosomes", a new liposome-like vaccine delivery system (R. Glück, A. Wegmann). Liposomes and virosomes as immunoadjuvant and antigen-carrier systems in vaccine formulations (T. Daemen et al.
). Theoretical basis for development of liposomes as carriers of vaccines (C.R. Alving). 3. Infectious Diseases.
The development of liposomal amphotericin B: An historical perspective (K.M. Wasan, G. Lopez-Berestein). Long-circulating liposomes containing antibacterial and antifungal agents (I.A.J.M. Bakker-Woudenberg, E.W.M. van Etten). Treatment of human immunodeficiency virus mycobacterium avium and mycobacterium tuberculosis infections by liposome-encapsulated drugs (N. Düzgünes). 4. Cancer Therapy.
Introduction and general strategies (D.D. Lasic, D. Papahadjopoulos). Designing therapeutically optimized liposomal anticancer delivery systems: Lessons from conventional liposomes (L.D. Mayer et al.
). Pharmacologic advantages of anthracyclines encapsulated in poly-ethylene-glycol coated stealth liposomes: Potential for tumor targeting (D. Goren, A. Gabizon). Cellular distribution of Doxil®
within selected tissues, assessed by confocal laser scanning microscopy (J. Vaage et al.
). Liposomes as carriers of lipophilic antitumor agents (R. Perez-Soler, Y. Zou). Targeted sterically stabilized liposomal drug delivery (T.M. Allen et al.
). Targeting of sterically stabilized liposomes to cancers overexpressing HER2 protooncogene (D.B. Kirpotin et al.
). 5. Gene Therapy.
Liposomes and gene delivery: A perspective (C. Nicolau, D. Papahadjopoulos). Cationic liposomes, DNA and gene delivery (D.D. Lasic, D. Ruff). Cationic liposomes - DNA complexes in gene therapy (S. Bhattacharya, L. Huang). Ultrastructural morphology of cationic liposome-DNA complexes for gene therapy (B. Sternberg). Liposomal antisense oligonucleotide therapeutics (M.C. Woodle, L. Leserman). 6. Other Applications.
Introduction (D.D. Lasic, D. Papahadjopoulos). Artificial lung expanding compound (ALECTM
) (A.D. Bangham). Pulmonary applications of liposomes (H. Schreier). Toxicity of liposome-encapsulated hemoglobin: Effect of liposomal membrane composition on host defense, platelet activation and hemostases during laminar shear flow (J. Jato et al.
). Developing uses of topical liposomes: Delivery of biologically active macromolecules (N. Weiner, L. Lieb). Liposomes as carriers of contrast agents for in vivo diagnostics (V.P. Torchilin). 7. Industrial Manufacturing and Pre-Clinical Testing.
Design of liposome-based drug carriers: From basic research to application as approved drugs (Y. Barenholz). Strategies for large scale production and optimised stability of pharmaceutical liposomes developed for parenterental use (E.C.A. van Winden et al.
). Pre-clinical studies of lipid-complexed and liposomal drugs: Amphotec Doxil®
and SPI-77 (P.K. Working). 8. Clinical Testing of Liposome Pharmaceuticals.
Clinical trials of liposomes as carriers of chemotherapeutic agents: Synopsis and perspective (A.A. Gabizon). Clinical pharmacology and antitumor efficacy of Doxil (pegylated liposomal doxorubicin): Sequus Pharmaceuticals, Inc. (F.J. Martin). The liposome company: Lipid-based pharmaceuticals in clinical development (C.E. Swenson et al.
). Unilamellar liposomes for anticancer and antifungal therapy: NeXstar Pharmaceuticals Inc. (P.G. Schmidt et al.
). Medical applications of multivesicular lipid-based particles: DepoFoamTM
encapsulated drugs, DepoTech, Inc. (J.H. Senior). 9. Future Prospects.
Future of liposome applications: Serendipity vs design (D.D. Lasic, D. Papahadjopoulos). List of Contributors. Subject Index.