Massage-induced release of subcutaneously injected liposome-encapsulated drugs to the blood.

Liposome-based, externally regulated drug delivery system is described in which liposome-encapsulated bioactive molecules can be delivered into the blood in response to simple mechanical action. Without any mechanical stimulation, subcutaneously injected 200 mm liposomes are usually trapped in the interstitial for prolonged time. However, upon lymphotropic stimulation (such as manual massage of the injection site), the liposomes can be mobilized into the blood via lymphatic pathway. Up to 40% of the injection dose can be delivered to the blood via lymphatic pathway from the injection site at the rabbit's front paw dorsum during 5 min manual massage cycle. Using vasoconstricting hormone angiotensin II as liposome-encapsulated pharmacological marker, we demonstrated that physiological response to encapsulated drug (average blood pressure increase) can also induced and modulated by massage. Massage itself was found to have no effect on the blood pressure. Modification of liposome surface with polyethylene glycol was found to increase blood localization of the liposome-encapsulated drug presumably due to decreasing the uptake of the drug carrier by lymph node macrophages. Pressure-dependent gaps between lymphatic capillary endothelial cells are thought to play the role of the size discrimination device allowing larger particulates into the lymphatics and, eventually into the blood after increase of interstitial pressure caused by injection site massage.

[Protective action of liposome-incorporated surface antigens of the influenza virus by different methods of immunization]. / Protektivnoe deistvie vkliuchennykh v liposomy poverkhnostnykh antigenov virusa grippa pri razlichnykh sposobakh immunizatsii.

The influence of different routes of immunization on the protective effect of liposome-incorporated influenza A/PR/8/34 virus surface antigens was studied. Influenza virus surface antigens, neuraminidase and hemagglutinin, incorporated into liposomes, were shown to have a significant protective effect upon intraperitoneal and intranasal administration against a lethal dose of influenza virus as compared with immunization using a free antigen solution against the same infection. The protective effect is poor in intravenous immunization with influenza virus antigen-containing liposomes. It is concluded that combining of influenza virus antigens with liposomes may be used for preparation of new influenza vaccines.

[Drug preparations of immobilized enzymes with enhanced affinity for the site of action]. / Lekarstvennye preparaty immobilizovannykh fermentov s povyshennym srodstvom k mestu deistviia.

Several approaches to development of systems for directed transport of drugs are illustrated by an example of thrombolytic therapy. Preparation and properties of enzyme derivatives with increased tropism to the thrombus material due to modification of enzymes by fibrinogen or specific antibodies are discussed. The data on directed transport of drugs under the action of the magnetic field and on the selective action of drugs on culture cells are also presented.