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.
Center for Imaging and Pharmaceutical Research, Massachusetts General Hospital-East, Charlestown. trubetskoy@worldnet.att.net
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Trubetskoy
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Whiteman
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Torchilin
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Wolf
D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood; D000818:Animals; D004337:Drug Carriers; D016503:Drug Delivery Systems; D007279:Injections, Subcutaneous; D008081:Liposomes; D008405:Massage; D011817:Rabbits
D004337:Drug Carriers; D008081:Liposomes; D000804:Angiotensin II