Fusogenic properties of saposin c and related proteins and peptides for application to transmembrane drug delivery systems

Abstract

The present invention comprises a method for delivering pharmaceutical and/or imaging agents within and/or through the dermal, mucosal and other cellular membranes, and across the blood-brain barrier, utilizing a fusogenic protein. The fusogenic protein is associated with a phospholipid membrane, such as a liposome. The liposome may include dioleoylphosphatidylserine, a negatively charged long-chain lipid. Alternatively, the liposome is comprised of a mixture of negatively charged long-chain lipids, neutral long-chain lipids, and neutral short-chain lipids. Preferred fusogenic proteins include saposin C and other proteins, polypeptides and peptide analogs derived from saposin C. The active agent contained within the liposome may comprise biomolecules and/or organic molecules. This technology can be used for both cosmetic and medicinal applications in which the objective is delivery of the active agent within and/or beneath biological membranes or across the blood-brain barrier and neuronal membranes.

1 .- 52 . (canceled) 
     
     
         53 . A method of delivering an agent to a disease, wherein the method comprises administering to a patient a composition comprising:
 a) a phosphatidylserine,   b) a safe and effective amount of the agent, and   c) a saposin C polypeptide;   wherein the disease is a brain cancer or a neuroblastoma.   
     
     
         54 . The method of  claim 53  wherein the administering of the composition comprises a mode of administration, wherein the mode of administration is selected from one or more of the list consisting of a transdermal patch, enteral delivery, trans-nasal delivery, intravenous delivery, intramuscular delivery and topical delivery. 
     
     
         55 . The method of  claim 54  wherein the mode of administration is intravenous delivery. 
     
     
         56 . The method of  claim 53  wherein the molar ratio of the saposin C-polypeptide to the phosphatidylserine is between about 1:7 and 1:50. 
     
     
         57 . The method of  claim 53  wherein the pH of the composition is between about 8 and 2. 
     
     
         58 . The method of  claim 53  wherein the agent is a pharmaceutical agent. 
     
     
         59 . The method of  claim 53  wherein the agent is an imaging agent. 
     
     
         60 . A method for treating a disease comprising delivering an agent through a biological membrane, wherein the method comprises administering to a patient a composition comprising:
 a) a phosphatidylserine,   b) a safe and effective amount of the agent, and   c) a saposin C polypeptide;   wherein the disease is a brain cancer or a neuroblastoma.   
     
     
         61 . The method of  claim 60  wherein the administering of the composition comprises a mode of administration, wherein the mode of administration is selected from one or more of the list consisting of a transdermal patch, enteral delivery, trans-nasal delivery, intravenous delivery, intramuscular delivery and topical delivery. 
     
     
         62 . The method of  claim 61  wherein the mode of administration is intravenous delivery. 
     
     
         63 . The method of  claim 60  wherein the molar ratio of the saposin C-polypeptide to the phosphatidylserine is between about 1:7 and 1:50. 
     
     
         64 . The method of  claim 60  wherein the pH of the composition is between about 8 and 2. 
     
     
         65 . The method of  claim 60  wherein the agent is a pharmaceutical agent. 
     
     
         66 . A method for delivering an agent across a membrane of the blood-brain barrier wherein the method comprises administration to the membrane a composition comprising:
 a) a phosphatidylserine,   b) a safe and effective amount of the agent, and   c) a saposin C polypeptide.   
     
     
         67 . The method of  claim 66  wherein the administering of the composition comprises a mode of administration, wherein the mode of administration is selected from one or more of the list consisting of a transdermal patch, enteral delivery, trans-nasal delivery, intravenous delivery, intramuscular delivery and topical delivery. 
     
     
         68 . The method of  claim 67  wherein the mode of administration is intravenous delivery. 
     
     
         69 . The method of  claim 66  wherein the molar ratio of the saposin C-polypeptide to the phosphatidylserine is between about 1:7 and 1:50. 
     
     
         70 . The method of  claim 66  wherein the pH of the composition is between about 8 and 2. 
     
     
         71 . The method of  claim 66  wherein the agent is a pharmaceutical agent. 
     
     
         72 . The method of  claim 66  wherein the agent is an imaging agent.