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THE PHARMA REVIEW (NOVEMBER - DECEMBER 2010)

Virosomal Drug Delivery: An Appraisal

Sanjib Bhattacharya1, Bhaskar Mazumder2

Abstract: Virosomes are reconstituted viral envelopes that can serve as vaccines and as vehicles for cellular delivery of various macromolecules. The prospect of drug delivery and targeting systems using virosomes is an interesting research and development field. Since virosomes are biocompatible, biodegradable, non-toxic and non-autoimmunogenuic; attempts have been made to utilize them as vaccines or adjuvants as well as delivery systems for drugs and biologicals for therapeutic purposes. Influenza virus is the most common virus of choice where virosomes are reconstituted influenza virus envelopes devoid of inner nucleic acid core and hence genetic information. The particulate structure and the function of the surface hemagglutinin protein of binding to the cell receptor, mediates pH-dependent membrane fusion leading to cellular delivery of the encapsulated biologically active molecule. The preparation and entrapment of bioactive molecules into the virosome remain the most important process. Characterization and dispensing of virosomes in suitable vehicles are further important steps for administration to humans. Virosomal vehicles could be utilized in vaccines, vaccine adjuvants; for the delivery of different bioactive molecules including peptides, nucleic acids or genes; drugs like antibiotics, antineoplastics, steroids etc. The present review provides a brief overview on virosomal drug delivery.

Introduction
Intense research and development efforts have produced invaluable drug moieties which promise relief from many dreadful disease conditions that were not possible earlier. However, finding out the drug moiety is only a part of the solution. Most of these new drugs do not lead themselves to easy fabrication with the existing and commonly used drug delivery technologies. Several drugs are discontinued at various stages of development process because of the lack of suitable delivery technologies. An appropriate drug delivery system may rescue some of the products by overcoming these difficulties. Furthermore, the new generation of therapeutics against cancer or neurogenerative disorders needs delivery systems which guarantee targeted drug delivery to specified host tissues, receptor-mediated uptake and controlled release into the cell. Present advancement in biotechnology and drug delivery technology is meeting these challenges with the development of a highly sophisticated carrier system based on virosomal technology.

Virosomes are reconstituted viral envelopes composed of membrane lipids and viral spike glycoproteins but devoid of viral genetic material i.e. DNA or RNA. The external surface of virosomes resembles that of virus particles with the spike proteins protruding from the membrane while the lumen of virosomes is empty. Preparation of virosomes was first reported by Almeida et al. (1975) by insertion of purified spike proteins of the influenza virus into pre-formed liposomes.1 Thereafter, reconstitution of a range of viral envelopes has been achieved including those of Sendai virus,2-4 Semliki Forest virus (SFV),5,6 vesicular stomatitis virus (VSV)7,8 and Sindbis virus.9 Since virosomes are virus-like particles, which display the viral envelope glycoproteins and thus the most important viral antigens for humoral immune responses in a native configuration, they are highly suitable to be used as vaccines10-12. Moreover, the receptor binding and membrane fusion properties of the viral envelope glycoprotein can be preserved which allows the use of virosomes as transport vehicles for cellular delivery of biologically active macromolecules.

 

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