Materials and methods for drug delivery and uptake

Abstract

The subject invention pertains to novel materials and methods for use in delivering and sequestering substances, such as pharmacological agents, within a patient. One aspect of the invention is directed towards core-shell particles having a core encapsulated within a calcium carbonate shell, with an intermediate layer composed of an amphiphilic compound surrounding the core. When the particles of the subject invention are administered to a patient, they are capable of removing lipophilic drugs by absorption of the drug through their mineral shell and into their core. The particles of the subject invention can also be administered to a patient as controlled release, drug delivery vehicles. Thus, in another aspect, the subject invention concerns a method of delivering pharmacological agents by administering the core-shell particles of the subject invention to a patient in need of such administration.

1 . A core-shell particle comprising: 
 (a) a shell, wherein said shell comprises calcium carbonate;    (b) a core; and    (c) an intermediate layer between said shell and said core, wherein said intermediate layer comprises an amphiphilic compound, and wherein said core and said intermediate layer are surrounded by said shell.    
   
   
       2 . A method for making a core-shell particle, wherein the method comprises the steps of: 
 (a) preparing a core; and    (b) encapsulating the core with a calcium carbonate shell.    
   
   
       3 . The method according to  claim 2 , wherein said step (a) comprises forming an emulsion droplet, and wherein said step (b) comprises contacting the emulsion droplet with a calcium-containing solution.  
   
   
       4 . The method according to  claim 3 , wherein the emulsion droplet comprises an oil phase and an amphiphilic compound, and wherein the core-shell particle comprises: 
 (a) the calcium carbonate shell;    (b) the core; and    (c) an intermediate layer between the calcium carbonate shell and the core, wherein the intermediate layer comprises the amphiphilic compound, and wherein the core and the intermediate layer are surrounded by the shell.    
   
   
       5 . The method according to  claim 4 , wherein the amphiphilic compound has a partially deprotonated carboxylic acid headgroup functionality.  
   
   
       6 . The method according to  claim 4 , wherein the amphiphilic compound is selected from the group consisting of stearic acid and arachidic acid.  
   
   
       7 . The method according to  claim 3 , wherein said method further comprises adding a source of Mg ion to the calcium-containing solution.  
   
   
       8 . The method according to  claim 3 , wherein said method further comprises adding a short-chained acidic polymer to the calcium-containing solution.  
   
   
       9 . The method according to  claim 8 , wherein the short-chained acidic polymer is selected from the group consisting of polyacrylic acid, polymethacrylate, sulfonated polymer, phosphorylated peptide, phosphorylated polymer, sulfated glycoprotein, polyaspartic acid, polyglutamic acid, and copolymers thereof.  
   
   
       10 . The method according to  claim 9 , wherein the short-chained acid polymer comprises poly-(α,β)-D,L-aspartic acid.  
   
   
       11 . The method according to  claim 8 , wherein the short-chained acid polymer is added at a concentration within the range of about 1 μg/ml and about 100 μg/ml.  
   
   
       12 . The method according. to  claim 3 , wherein said forming an emulsion droplet comprises contacting a hydrophobic compound with an aqueous solution.  
   
   
       13 . The method according to  claim 12 , wherein said forming an emulsion droplet further comprises adding an amphiphilic compound to the aqueous solution.  
   
   
       14 . The method according to  claim 13 , wherein the amphiphilic compound is selected from the group consisting of stearic acid and arachidic acid.  
   
   
       15 . The method according to  claim 3 , wherein the calcium-containing solution comprises CaCl 2 .  
   
   
       16 . The method according to  claim 3 , wherein the calcium-containing solution further comprises Mg.  
   
   
       17 . The method according to  claim 3 , wherein the calcium-containing solution further comprises MgCl 2 .  
   
   
       18 . The method according to  claim 17 , wherein the calcium-containing solution further comprises CO 3   2−  counterion.  
   
   
       19 . The method according to  claim 17 , wherein said method further comprises adding CO 3   2−  counterion to the calcium-containing solution.  
   
   
       20 . The method according to  claim 19 , wherein the CO 3   2−  counterion is added to the calcium-containing solution by peristaltic pumping.  
   
   
       21 . A method for sequestering a lipophilic agent within a patient comprising administering an effective amount of core-shell particles to the patient, wherein the core-shell particles comprise: 
 (a) a shell, wherein the shell comprises calcium carbonate;    (b) a core; and    (c) an intermediate layer between the shell and the core, wherein the intermediate layer comprises an amphiphilic compound, and wherein the core and the intermediate layer are surrounded by the shell.    
   
   
       22 . The method according to  claim 21 , wherein the core is hollow.  
   
   
       23 . The method according to  claim 21 , wherein the core comprises an oil.  
   
   
       24 . The method according to  claim 23 , wherein the core further comprises an enzyme that degrades the lipophilic agent.  
   
   
       25 . The method according to  claim 21 , wherein the enzyme comprises a cytochrome P450 enzyme.  
   
   
       26 . The method according to  claim 24 , wherein the lipophilic agent is absorbed into the core-shell particles, and wherein the enzyme subsequently degrades the lipophilic agent.  
   
   
       27 . The method according to  claim 21 , wherein the core-shell particles are administered to the patient intravenously.  
   
   
       28 . The method according to  claim 21 , wherein a toxic amount of the lipophilic agent is present within the patient prior to said administration of the core-shell particles.  
   
   
       29 . The method according to  claim 24 , wherein the enzyme is adsorbed onto the shell of the particles.  
   
   
       30 . A method for sequestering a lipophilic agent from the surrounding environment comprising contacting an effective amount of core-shell particles with the lipophilic agent, wherein the core-shell particles comprise: 
 (a) a shell, wherein the shell comprises calcium carbonate;    (b) a core; and    (c) an intermediate layer between the shell and the core, wherein the intermediate layer comprises an amphiphilic compound, and wherein the core and the intermediate layer are surrounded by the shell.    
   
   
       31 . The method according to  claim 30 , wherein said contacting is carried out in vivo.  
   
   
       32 . The method according to  claim 30 , wherein the surrounding environment is a patient's bloodstream.  
   
   
       33 . A method for delivering a biologically active agent to a patient comprising administering an effective amount of core-shell particles to the patient, wherein the core-shell particles comprise: 
 (a) a shell, wherein the shell comprises calcium carbonate;    (b) a core, wherein said core comprises a biologically active agent; and    (c) an intermediate layer between the shell and said core, wherein said intermediate layer comprises an amphiphilic compound, and wherein said core and said intermediate layer are surrounded by said shell.