Chemistry: molecular biology and microbiology – Virus or bacteriophage – except for viral vector or...
Patent
1992-11-02
2000-03-21
Brusca, John S.
Chemistry: molecular biology and microbiology
Virus or bacteriophage, except for viral vector or...
4241791, 424450, 4353881, 4353888, 4353891, 4353897, 4353911, 514 2, 530350, C12N 700, A61K 9127, A61K 39395, C07K 1411
Patent
active
060401672
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The invention relates to synthetic membrane vesicles (liposomes) and particularly to vesicles exhibiting on their surface fusion peptide molecules and other cell-specific proteins. The fusion peptide molecule may be in the form of a synthetic or purified peptide or as a part of a spike glycoprotein molecule of an enveloped virus, e.g. hemagglutinin, such as of influenza, parainfluenza or Semliki Forest virus. The cell-specific protein may be an IgG antibody, e.g. the CD4 antibody.
DESCRIPTION OF RELATED ART
When a drug is given to a subject it must usually pass from the site of administration in to the plasma compartment, and therefore the route of administration may have an important effect on the pharmacokinetic profile of the drug in the circulation. Thus, oral administration of the drug, while convenient, results in a slow onset of drug action and is somewhat unreliable in terms of achieving optimum plasma drug levels. By contrast, intravenous injection results in the prompt and exact establishment of circulating levels, at the cost of some pain and inconvenience to the patient. However, even if the drug is injected directly into the systemic circulation, the relationship between administered dose, drug levels and duration of the target site is by no means simple. These parameters are determined by a complex and often competing network of pathways leading either to accumulation of active drug molecules at the target site, or to the inactivation and excretion of the drug. These pathways involve biotransformation in the liver and in other tissues, excretion via the kidney or the bile, binding of drugs to fixed or circulating cells or macromolecules, and the passive or mediated passage of the drug across membrane barriers (Creasy, W. A. (1979): Drug Disposition in Humans, Oxford Univeristy Press, New York).
In recent years, there has been a good deal of interest in the prospect of influencing the distribution and metabolism of drugs in beneficial ways by using various sorts of carrier or drug delivery systems. These systems are designed to control one or more of the following parameters (Juliano, R. R. (1975), Can. J. Physiol. Pharmaco 56, 683-690):
a) the rate of input of the drug into a particular body compartment;
b) the distribution and localization of the drug in the body;
c) the persistence or rate of metabolism of the drug.
A major improvement in controlled drug delivery systems was the development of liposomes which were first described by Bangkam et al. (Bangkam, A. D., Standish, M. M. and Watkins, J. C. (1965), J. Mol. Biol. 13, 238-252). Today, the literature claims an extravagant variety of benefits to be gained by delivering particular drugs in liposomes. These can be loosely grouped under the following headings:
1. Liposomes may cross biomembranes and may facilitate the transport of drugs through normally impermeable barriers. In particular, liposomes facilitate the intracellular penetration of encapsulated compounds.
2. Liposomes may be designed to interact with specific tissues, improving drug selectivity and reducing toxicity.
3. Drug pharmacokinetics may be beneficially modified by liposomes, through modulation of drug release, distribution and removal from the systemic circulation.
4. Chemically and metabolically labile drugs may be protected by liposomes from deactivation.
Drugs of potential therapeutic interest may be sequestered in this way, the encapsulated compounds exhibiting modified properties, at least in vitro, when compared with the unmodified substances. Unfortunately, early hopes of a revolutionary new approach to chemotherapy have not been completely realised by the experimental facts (Fildes, F. J. T. (1981), Liposomes. From physical structure to therapeutic applications. Knight (ed.), Elsevier/North-Holland Biomedical Press).
A better result using liposomes as vectors could be achieved by the targetting of liposomes with specific proteins. If substances encapsulated in liposomes were to be delivered more successfully to selected organs or tissu
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Gluck Reinhard
Herrmann Peter
Klein Peter
Walti Ernst Rudolf
Brusca John S.
Nika Health Products Limited
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