Dehydration-rehydration Vesicles Research Articles

Incorporation of reconstituted influenza virus envelopes into liposomes: studies of the immune response in mice

Conference Article| February 01 1989 Incorporation of reconstituted influenza virus envelopes into liposomes: studies of the immune response in mice LLOYD TAN; LLOYD TAN *Medical Research Council Group, Academic Medicine, Royal Free Hospital School of Medicine, London NW3 2QG, U.K. Search for other works by this author on: This Site PubMed Google Scholar ABRAHAM LOYTER; ABRAHAM LOYTER †Department of Biochemistry, Hebrew University of Jerusalem, Jerusalem, Israel Search for other works by this author on: This Site PubMed Google Scholar GREGORY GREGORIADIS GREGORY GREGORIADIS *Medical Research Council Group, Academic Medicine, Royal Free Hospital School of Medicine, London NW3 2QG, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1989) 17 (1): 129–130. https://doi.org/10.1042/bst0170129 Article history Received: June 22 1988 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation LLOYD TAN, ABRAHAM LOYTER, GREGORY GREGORIADIS; Incorporation of reconstituted influenza virus envelopes into liposomes: studies of the immune response in mice. Biochem Soc Trans 1 February 1989; 17 (1): 129–130. doi: https://doi.org/10.1042/bst0170129 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: DRV, dehydration-rehydration vesicle, RIVE, reconstituted influenza virus envelope, PC, phosphatidylcholine, DSPC, distearoyl phosphatidylcholine, PBS, phosphate-buffered saline, ELISA, enzyme-linked immunosorbent assay This content is only available as a PDF. © 1989 Biochemical Society1989 Article PDF first page preview Close Modal You do not currently have access to this content.

Contrast-carrying liposomes. Current status.

The goal of recent research has been to encapsulate standard, water-soluble radiographic contrast media (RCM) into liposomes, in order to direct them to reticuloendothelial tissues. Toward this end several varieties of contrast-carrying liposomes (CCLs) have been prepared. Each of these has proven effective in opacifying the liver and spleen of animals on computed tomography (CT). The suitability of two new encapsulation techniques: (1) Microemulsification (MELs), and (2) Dehydration Rehydration Vesicles (DRVs), for CCL production has been explored recently. Each of these two new preparative techniques were valuable in the effort to "scale-up" the CCL production process, leading to "pharmaceutically acceptable" preparation.

Evaluation of the dehydration-rehydration method for production of contrast-carrying liposomes.

We measured the amounts of three types of radiographic contrast media (RCM) that could be entrapped in liposomes prepared by the dehydration-rehydration vesicle (DRV) technique. To make DRVs, one initially makes water-containing, small unilamellar vesicles, adds contrast media and lyophilizes the mixture. Upon rehydration, the DRVs re-form, passively entrapping RCM. Diatrizoate, iohexol and iotrolan proved to be entrappable in similar amounts (diatrizoate was best), but all of these amounts were less than for other small molecules, such as carboxyfluorescein (P less than 0.05). Entrapment was directly proportional to lipid concentration (r = 0.76; P less than 0.002), and inversely related to iodine concentration (r = 0.86; P less than 0.002). Under ideal conditions with neutral lipids, 19.45 +/- 9.9% of diatrizoate was entrapped, corresponding to 1.05 +/- 0.50 g I per g lipid. These values are close to those achievable for large unilamellar vesicles. Use of an automated mixing device (the Microfluidizer) in place of sonication, facilitated production of large liposome batches and improved entrapment (P less than 0.05). Computed tomography (CT) scans of rats showed 30 and 218 HU of liver and spleen enhancement, respectively, per g I/kg injected DRVs. These studies showed this method (possible augmented by the Microfluidizer) allows efficient production of contrast-carrying liposomes.

Liposomes as adjuvants with immunopurified tetanus toxoid: the immune response

Immune responses of BALB/c mice to immunopurified tetanus toxoid entrapped in dehydration-rehydration vesicles composed of equimolar egg phosphatidylcholine and cholesterol were compared to those of free toxoid. Animals were injected intramuscularly with the free or liposomal toxoid and identical injections were repeated 4 weeks and, in some experiments, 24 weeks later. Analysis of IgG 1, IgG 2a, IgG 2b, IgG 3 and IgM in the sera by an enzyme-linked immunosorbent assay suggested that adjuvanticity of liposomes is reflected in most antibody subclasses and that there is no shift in subclasses compared to the response obtained with the free antigen, thus establishing liposomes as a type I adjuvant. In other, appropriately designed experiments, the relative importance of events following the first and second injections in determining the adjuvant effect of liposomes was investigated. It was found that liposome adjuvanticity is the outcome of events following primary immunization.

Targeting of drug loaded immunoliposomes to herpes simplex virus infected corneal cells: an effective means of inhibiting virus replication in vitro.

The goal of our studies was to develop liposomes containing antiviral drugs and targeted with antiviral antibody (immunoliposomes) that would be effective at inhibiting replication of herpes simplex virus (HSV) in vitro. To achieve this, a monoclonal antibody to glycoprotein D of HSV was derivatized with palmitic acid and was incorporated into the lamellae of dehydration-rehydration vesicles. The gD containing immunoliposomes were shown to bind specifically to HSV-infected rabbit corneal cells in vitro, whereas control immunoliposomes prepared with a monoclonal antibody of the same class as the anti-gD failed to preferentially bind to virus-infected cells. The gD immunoliposome binding was inhibitable by pretreatment with rabbit anti-HSV serum but not by aggregated normal serum. Thus liposome binding was judged to represent an antigen-antibody reaction not binding to Fc receptors expressed by cells infected with HSV. Immunoliposomes loaded with iododeoxyuridine (IUDR) leaked drug rapidly at 37 degrees C, whereas acyclovir (ACV)-loaded liposomes still contained 48% of drug after 24 hr at 37 degrees C. The ACV-liposomes retained 44% of drug after 14 days at 4 degrees C. The ability of immunoliposomes to inhibit virus replication was compared with that of untargeted and empty liposomes by means of virus yield assays in vitro, Immunoliposomes loaded with either IUDR or ACV inhibited virus replication, although ACV-containing immunoliposomes were the most efficacious. The implications of our in vitro results for the development of immunoliposomes suitable for the treatment of ocular herpes infection are briefly discussed.