Phosphatidylcholine lipid liposomes as boundry lubricants in aqueous media

Abstract

The invention provides a method for lubricating one or more surfaces, comprising applying gel-phase liposomes onto said one or more surfaces, wherein the temperature of said surface(s) at the time of lubrication is below the phase transition temperature Tm of said liposomes. The method can be used for lubricating non-biological surfaces, and also for lubricating the surfaces of a biological tissue in a mammalian subject, e.g., for treating joint dysfunction.

1 . A method for lubricating one or more non-biological surfaces, comprising applying gel-phase liposomes onto said one or more surfaces, wherein the temperature of said surface (s) at the time of lubrication is below the liquid-crystalline to gel-phase transition temperature T m  of said liposomes. 
     
     
         2 . The method according to  claim 1 , wherein the gel-phase liposomes comprise one or more phosphatidylcholine lipids, with the phase transition temperature T m  of the liposomes being not less than 40° C. 
     
     
         3 . The method according to  claim 2 , wherein the gel-phase liposomes have phase transition temperature which is not less than 45° C. 
     
     
         4 . The method according to  claim 3 , wherein the gel-phase liposomes comprise lipids selected from the group consisting of hydrogenated soy phosphatidylcholine (HSPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and mixtures thereof. 
     
     
         5 . The method according to  claim 1 , wherein the gel-phase liposomes have external polar head groups which are composed of at least 95 mole % phosphocholine groups, and of up to 5 mole % external non-phosphocholine head groups having an unperturbed-end-to-end radius in aqueous medium equal to or smaller than about 1 nm. 
     
     
         6 . The method according to  claim 5 , wherein the gel-phase liposomes comprise a first lipid, which is phosphocholine-containing lipid selected from the group consisting of HSPC, DSPC, dipalmitoylphosphatidylcholine (DPPC) and mixtures thereof, and a second lipid, which carries trimethylammonium-propane (TAP) hydrophilic head group. 
     
     
         7 . The method according to  claim 6 , wherein the TAP-containing lipid is selected from the group consisting of 1,2 ditetradecanoyl-3-trimethylammonium-propane (DMTAP), 1,2 dipalmitoyl-3-dimethylammonium-propane and 1,2-disteraroyl-3 dimethylammonium-propane. 
     
     
         8 . The method according to  claim 1 , wherein the gel-phase liposomes are in the form of small unilamellar vesicles (SUV) and have a mean diameter which is smaller than 100 nm. 
     
     
         9 . The method according to  claim 1 , wherein the gel-like liposomes are in the form of multilamellar vesicles (MLVs) and have a mean diameter which is larger than 200 nm. 
     
     
         10 . The method according to  claim 1 , wherein the liposomes are applied in an aqueous medium which is an aqueous salt solution. 
     
     
         11 . The method according to  claim 1 , wherein the surface to be lubricated is negatively-charged. 
     
     
         12 . A method for lubricating one or more surfaces of a biological tissue in a mammalian subject, comprising applying gel-phase liposomes onto said one or more surfaces, wherein the temperature of said surface (s) at the time of lubrication is below the phase transition temperature T m  of said liposomes. 
     
     
         13 . A method according to  claim 12 , wherein the surface is within a joint capsule. 
     
     
         14 . The method according to  claim 13 , wherein the pressure within the joint reaches values higher than 30 atm (3 MPa). 
     
     
         15 . The method according to  claim 12 , wherein the gel-phase liposomes comprise one or more phosphatidylcholine lipids, with the phase transition temperature T m  of the liposomes being not less than 40° C. 
     
     
         16 . The method according to  claim 15 , wherein the gel-phase liposomes have phase transition temperature which is not less than 45° C. 
     
     
         17 . The method according to  claim 16 , wherein the gel-phase liposomes comprise lipids selected from the group consisting of hydrogenated soy phosphatidylcholine (HSPC), 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and mixtures thereof. 
     
     
         18 . The method according to  claim 12 , wherein the gel-phase liposomes have external polar head groups which are composed of at least 95 mole % phosphocholine groups, and of up to 5 mole % external non-phosphocholine head groups having an unperturbed-end-to-end radius in aqueous medium equal to or smaller than about 1 nm. 
     
     
         19 . The method according to  claim 18 , wherein the gel-phase liposomes comprise a first lipid, which is phosphocholine-containing lipid selected from the group consisting of HSPC, DSPC, DPPC and mixtures thereof, and a second lipid, which carries trimethylammonium-propane (TAP) hydrophilic head group. 
     
     
         20 . The method according to  claim 19 , wherein the TAP-containing lipid is selected from the group consisting of 1,2 ditetradecanoyl-3-trimethylammonium-propane (DMTAP), 1,2 dipalmitoyl-3-dimethylammonium-propane and 1,2-disteraroyl-3 dimethylammonium-propane. 
     
     
         21 . Method according to  claim 12 , wherein the gel-phase liposomes are in the form of small unilamellar vesicles (SUV) and have a mean diameter which is smaller than 100 nm. 
     
     
         22 . The method according to  claim 12 , wherein the gel-like liposomes are in the form of multilamellar vesicles (MLVs) and have a mean diameter which is larger than 200 nm. 
     
     
         23 . The method according to  claim 12 , wherein the liposomes are applied in an aqueous medium which is a physiologically acceptable solution. 
     
     
         24 . Use of gel-phase liposomes in the preparation of a therapeutic composition for the treatment of joint dysfunction in a mammalian subject by means of the lubrication of surface (s) within the joint capsule, wherein the temperature of said surfaces at the time of lubrication is below the phase transition temperature T m  of said liposomes. 
     
     
         25 . Gel-phase liposomes for the treatment of joint dysfunction in a mammalian subject by means of the lubrication of surface (s) within the joint capsule, wherein the temperature of said surfaces at the time of lubrication is below the phase transition temperature T m  of said liposomes. 
     
     
         26 . Use according to  claim 24 , wherein the pressure within the joint reaches values higher than 30 atm (3 MPa). 
     
     
         27 . A mixed liposome suitable for use as a lubricant comprising a first lipid, which is phosphocholine-containing lipid and a second lipid, which contains TAP hydrophilic head group, wherein the mole ratio between said first and second lipids is from 95:5 to 99.9:0.1. 
     
     
         28 . A mixed liposome according to  claim 27 , wherein the TAP-containing lipid has two hydrocarbon chains which independently contain 14, 16 or 18 carbon atoms. 
     
     
         29 . A mixed liposome according to  claim 28 , wherein the first lipid is HSPC and wherein the TAP-containing lipid is selected from the group consisting of 1,2-ditetradecanoyl-3-trimethylammonium-propane (DMTAP), 1,2-dipalmitoyl-3-dimethylammonium-propane and 1,2-disteraroyl-3-dimethylammonium-propane.