Lisbeth Illum

Delivery systems for peptide drugs

Advanced Delivery Systems for Peptides and Proteins - Pharmaceutical Considerations.- Biotechnology and Protein Production.- Peptide Analysis: Critical Technology for Evaluating Delivery Approaches.- Bioreversible Derivatization of Peptides.- An Approach to Target Therapy. Synthesis and Biological Activity of Hydrophobic and Hydrophilic Enkephalin Analogues.- Temporal and Pharmacokinetic Aspect in Delivery of Peptides and Proteins.- Enzymatic Barriers to Peptide and Protein Absorption and the Use of Penetration Enhancers to Modify Absorption.- Intracellular Sorting of Proteins.- Biodegradable Polymers for Sustained Release of Polypeptides.- Controlled Delivery of Nafarelin, an Agonistic Analogue of LHRH, From Microspheres of Poly (D, L Lactic-Co-Glycolic) Acid.- The Oral Bioavailability of Peptides and Related Drugs.- Oral Delivery of Peptide Drugs.- Drug Delivery of Peptides: The Buccal Route.- Enhanced Absorption and Lymphatic Transport of Macromolecules via the Rectal Route.- Biopharmaceutical Aspects on the Intranasal Administration of Peptides.- Microspheres as a Potential Controlled Release Nasal Drug Delivery System.- NazlinR - Transnasal Systemic Delivery of Insulin.- Nasal Absorption of Enkephalins in Rats.- Intranasal Delivery of the Peptide, Salmon Calcitonin.- Metabolic Effects of Intranasally Administered Insulin and Glucagon in Man.- Human Calcitonin Administered by the Nasal Route: Bioavailability of Different Formulations and Efficacy in Post-Menopausal Osteoporosis.- Routes of Administration for Polar Compounds of Moderate Molecular Weight with Particular Reference to Analogues of Somatostatin.- The Transdermal Route for the Delivery of Peptides and Proteins.- Controlled-Release and Localized Targeting of Interferons.- Delivery of Macrophage Activating Factors by Means of Liposomes.- Activators of Plasminogen.- Biosynthetic Human Growth Hormone Identical to Authentic Material.- Delivery Systems for Recombinant Methionyl Human Growth Hormone.- Eledoisin and Ceruletide, Two Naturally Occurring Peptide Drugs of Nonmammalian Origin.- Consideration of the Proteins and Peptides Produced by New Technology for use as Therapeutics.- Key Issues in the Delivery of Peptides and Proteins.- Photo.- Contributors.

Drug-polyionic block copolymer interactions for micelle formation: physicochemical characterisation.

While covalent attachment of small drug molecules to AB copolymers for the formation of polymeric micelles for drug delivery has been investigated, few studies have focused on non-covalent interactions. The aim of this study was therefore to explore the potential of non-covalent interactions between an AB copolymer, Poly(aspartic acid)-poly(ethylene glycol) (Pasp-PEG), with anionic pendant groups and diminazene aceturate, a small molecular weight cationic drug. Micelles were prepared by mixing solutions of Pasp-PEG and diminazene in 25 mM Tris-HCl buffer. At all Pasp-PEG concentrations studied, the micelles appeared to be water soluble with a unimodal size distribution and ranged in size from approximately 22 to 60 nm. The polyionic micelles also displayed similar and small absolute zeta potential values at various drug:monomer molar ratios which confirmed stabilisation by the PEG corona. The scattering intensity was maximal and remained unchanged, while particle size increased slightly at pH range from 3.4 to 7.2. At this pH range both the polymer and drug would be ionised and ionic interactions possible to drive micellar formation. An increase in size and scattering intensity with addition of NaCl to the micelles was attributed to dehydration of the PEG corona which may have led to aggregation of the micelles. The absence of micellar dissociation upon addition of salt was attributed to the dominance of hydrogen bonding between Pasp and diminazene aceturate, as assessed by isothermal titration microcalorimetry. Morphological evaluation of these constructs showed them to be discrete and fairly uniform in size and shape. This study was therefore successful in confirming the potential of non-covalent interactions using an AB copolymer to form polyionic micelles for drug delivery.

A sustained delivery system for intramuscular administration of lipophilic drugs using globular partially quaternised poly[thio-1-(N,N-diethyl aminomethyl)-1-ethylene]

Abstract A novel globular partially quaternised polymer system has been used to administer a radio-labelled steroid, 75 Se-norcholestenol, intramuscularly; solution and micellar systems were used as controls. Release of the steroid from the injection site and its accumulation in the liver was followed by the non-invasive technique of gamma scintigraphy. The polymer was able to entrap the steroid (>98%) at physiological pH and thereby provide a sustained release over a period of 30 days. The labelled compound was released more rapidly from the solution and the micellar system and, contrary to the polymer system, significant accumulation was observed in the liver.

Application of novel biomaterials in colloidal drug delivery systems.

The development of biomaterials to treat, repair, or reconstruct the human body is an increasingly important component of materials research. Collaboration between materials researchers and their industrial and clinical partners is essential for the development of this complex field. To demonstrate the importance of these interactions, two articles in this issue focus on advances in biomaterials relating to the use of colloidal systems for transport, drug delivery, and other medical applications. These articles were coordinated by Dominique Muster (Universite Louis Pasteur, Strasbourg) and Franz Burny (Hopital Erasme, Brussels). The following is the second of these two articles . There are two important objectives in drug delivery research. The first is to maximize the effectiveness of drugs by increasing the amount of drug reaching the target tissue while sparing other tissues the deleterious effects of the drug. The second is to control the release of a drug, so that the period of optimal drug concentration in the target tissue is maximized. A numbe r of different Systems have been investigated to achieve these objectives, including soluble polymeric delivery Systems and a range of colloidal drug delivery forms such as liposomes, emulsions, micelles, microcapsules, microparticles, and nanoparticles. This article focuses on polymeric materials for the production of micro- or nanoparticle Systems for dru g delivery by injection, and their characterization and Performance in vivo . Colloidal particles have a number of advantages as drug delivery Systems; they are easy to prepare, have the potential for high drug loading, and release of the drug can be controlled. However, without surface modification, colloidal particles are difficult to target because they are directed largely to the liver and spieen after intravenous injection. The reasons for this can be found in the context of the bodys defenses. In order to protect against disease, the body has a complex System to ensure that invading microorganisms are identified and neutralized at the earliest possible opportunity. Most parasitic or invading organisms which pose a threat are particulate in form, and thus any colloidal drug delivery System will have to evade detection by these mechanisms in order to reach its target.