The chapters in this volume describe a powerful emerging approach for the therapy of disease. Targeted drug delivery, that is control of the kinetic behavior, tissue distribution, and subcellular localization of pharmaco logically active agents, offers an important means for improving the efficacy of a wide variety of drug therapies. This is particularly true for therapeutic approaches based on newer agents which are the products of recombinant DNA research. These agents, be they peptides, proteins, or oligonucleotides, tend to be larger, more complex, and less stable than traditional drugs.…mehr
The chapters in this volume describe a powerful emerging approach for the therapy of disease. Targeted drug delivery, that is control of the kinetic behavior, tissue distribution, and subcellular localization of pharmaco logically active agents, offers an important means for improving the efficacy of a wide variety of drug therapies. This is particularly true for therapeutic approaches based on newer agents which are the products of recombinant DNA research. These agents, be they peptides, proteins, or oligonucleotides, tend to be larger, more complex, and less stable than traditional drugs. Thus they stand to benefit most from drug delivery systems which can protect them from premature degradation and which can carry them to critical target sites in the body. This volume examines several important aspects of the current state of drug delivery research; it also attempts to project future directions for this field. Successful approaches to drug targeting are based, first of all, on a sophisticated understanding of the biological barriers encountered by the drug-carrier complex as it moves from the portal of administration to the ultimate target site. A second aspect of successful drug delivery is appro priate matching of the disease entity with the pharmacologically active substance and with the delivery system. Thus it is important to be aware of the variety of delivery technologies which currently exist and to be sensitive to their strengths and limitations.
1 A New Perspective for Drug Delivery Research.- A. Promises Realized: A Recent History of Controlled Drug Delivery.- B. The Opening Door: Molecular Biology Generates New Opportunities and Challenges for Drug Delivery Research.- C. An Overview of this Volume: Building on the Past and Looking Toward the Future.- D. Drug Targeting Research in the Twenty-First Century: A New Perspective.- References.- 2 Internalization and Sorting of Macromolecules: Endocytosis.- A. Introduction.- B. Pathways of Endocytosis in Nonpolarized Cells.- C. Molecular Basis of Endocytosis.- D. Noncoated Pit Internalization.- E. Endocytosis in Polarized Cells.- F. Summary.- References.- 3 Transport of Macromolecules Across the Capillary Endothelium.- A. Introduction.- B. Pathways for the Passage of Macromolecules Across Capillary Endothelium.- C. The Blood-Brain Barrier.- D. Experimental Model Systems.- E. Applications of Tissue Culture Models in the Study of Capillary Endothelial Cell Transport of Macromolecules.- F. Summary.- References.- 4 Pharmacokinetics of Drug Targeting: Specific Implications for Targeting via Prodrugs.- A. Introduction.- B. Pharmacokinetic Models and Drug Targeting.- C. Prodrug-Mediated Targeted Drug Delivery.- References.- 5 Soluble Polymers as Targetable Drug Carriers.- A. Introduction.- B. Consequences of Drug Binding to Macromolecular Carriers: Cellular Level.- C. Fate of Macromolecular Carriers In Vivo.- D. Release of Drugs.- E. Targeting.- F. Photosensitization: Activation by Light.- G. Decreased Toxicity and Immunogenicity of Drug-Polymer Conjugates.- H. Soluble Polymers for Site Specific Oral Drug Delivery.- I. Concluding Remarks.- References.- 6 Systemic Delivery of Pharmacologically Active Molecules Across the Skin.- A. Biomedical Logic of Transdermal Drug Delivery.- B. Historic Development of TDD.- C. Transdermal Delivery of Pharmacologically Active Organic Molecules.- D. Transdermal Delivery of Pharmacologically Active Peptide/Protein Molecules.- E. Conclusion.- References.- 7 Chemical Delivery Systems.- A. Introduction.- B. Site and Stereospecific Drug Delivery to the Eye.- C. Brain-Targeting Drug Delivery.- References.- 8 In Vivo Behavior of Liposomes: Interactions with the Mononuclear Phagocyte System and Implications for Drug Targeting.- A. Introduction.- B. Interactions with Body Fluids.- C. Interactions with Cells.- D. Anatomical Barriers.- E. Factors Influencing Liposome Uptake by Cells.- F. Surface Modification.- G. Intracellular Processing of Liposomes.- H. Implications for Drug Targeting.- I. Concluding Remarks.- References.- 9 Antisense Oligonucleotides as Pharmacological Modulators of Gene Expression.- A. General Principles and Historical Background.- B. Artificial Control of Gene Expression by Synthetic Oligonucleotides: An Overview of Problems and Potential.- C. Oligonucleotide Chemistry and Modifications.- D. Internalization Pathway of Antisense Oligonucleotides and Alternative Methods to Increased Cellular Uptake.- E. Mechanism of Action of Antisense Oligonucleotides.- F. Biological Potential of Synthetic Oligonucleotides.- G. Prospectives of In Vivo Utilization of Antisense Oligonucleotides.- References.
1 A New Perspective for Drug Delivery Research.- A. Promises Realized: A Recent History of Controlled Drug Delivery.- B. The Opening Door: Molecular Biology Generates New Opportunities and Challenges for Drug Delivery Research.- C. An Overview of this Volume: Building on the Past and Looking Toward the Future.- D. Drug Targeting Research in the Twenty-First Century: A New Perspective.- References.- 2 Internalization and Sorting of Macromolecules: Endocytosis.- A. Introduction.- B. Pathways of Endocytosis in Nonpolarized Cells.- C. Molecular Basis of Endocytosis.- D. Noncoated Pit Internalization.- E. Endocytosis in Polarized Cells.- F. Summary.- References.- 3 Transport of Macromolecules Across the Capillary Endothelium.- A. Introduction.- B. Pathways for the Passage of Macromolecules Across Capillary Endothelium.- C. The Blood-Brain Barrier.- D. Experimental Model Systems.- E. Applications of Tissue Culture Models in the Study of Capillary Endothelial Cell Transport of Macromolecules.- F. Summary.- References.- 4 Pharmacokinetics of Drug Targeting: Specific Implications for Targeting via Prodrugs.- A. Introduction.- B. Pharmacokinetic Models and Drug Targeting.- C. Prodrug-Mediated Targeted Drug Delivery.- References.- 5 Soluble Polymers as Targetable Drug Carriers.- A. Introduction.- B. Consequences of Drug Binding to Macromolecular Carriers: Cellular Level.- C. Fate of Macromolecular Carriers In Vivo.- D. Release of Drugs.- E. Targeting.- F. Photosensitization: Activation by Light.- G. Decreased Toxicity and Immunogenicity of Drug-Polymer Conjugates.- H. Soluble Polymers for Site Specific Oral Drug Delivery.- I. Concluding Remarks.- References.- 6 Systemic Delivery of Pharmacologically Active Molecules Across the Skin.- A. Biomedical Logic of Transdermal Drug Delivery.- B. Historic Development of TDD.- C. Transdermal Delivery of Pharmacologically Active Organic Molecules.- D. Transdermal Delivery of Pharmacologically Active Peptide/Protein Molecules.- E. Conclusion.- References.- 7 Chemical Delivery Systems.- A. Introduction.- B. Site and Stereospecific Drug Delivery to the Eye.- C. Brain-Targeting Drug Delivery.- References.- 8 In Vivo Behavior of Liposomes: Interactions with the Mononuclear Phagocyte System and Implications for Drug Targeting.- A. Introduction.- B. Interactions with Body Fluids.- C. Interactions with Cells.- D. Anatomical Barriers.- E. Factors Influencing Liposome Uptake by Cells.- F. Surface Modification.- G. Intracellular Processing of Liposomes.- H. Implications for Drug Targeting.- I. Concluding Remarks.- References.- 9 Antisense Oligonucleotides as Pharmacological Modulators of Gene Expression.- A. General Principles and Historical Background.- B. Artificial Control of Gene Expression by Synthetic Oligonucleotides: An Overview of Problems and Potential.- C. Oligonucleotide Chemistry and Modifications.- D. Internalization Pathway of Antisense Oligonucleotides and Alternative Methods to Increased Cellular Uptake.- E. Mechanism of Action of Antisense Oligonucleotides.- F. Biological Potential of Synthetic Oligonucleotides.- G. Prospectives of In Vivo Utilization of Antisense Oligonucleotides.- References.
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