A solid nanoparticle with inorganic coating

Abstract

A nanoparticle having a solid core comprising a biologically active substance, said core being enclosed by an inorganic coating, a method for preparing the nanoparticle, and the use of the nanoparticle in therapy. A kit comprising the nanoparticle and a pharmaceutical composition comprising the nanoparticle.

1 . A method of preparing a plurality of coated nanoparticles, said coated nanoparticles having a solid core comprising a biologically active substance, said solid core being enclosed by an inorganic coating; the method comprising
 applying one or more layers of inorganic material to a plurality of said solid cores by an application method wherein the inorganic material and/or precursors for forming the inorganic material is/are present in gas phase, and   submitting said solid cores to agitation during and/or in between application of the layer(s) of inorganic material.   
     
     
         2 . The method of  claim 1 , wherein more than one layer of inorganic material is applied to said solid cores and said solid cores are submitted to agitation after applying at least one layer of inorganic material to said solid cores and before applying at least one subsequent layer of inorganic material to said solid cores. 
     
     
         3 . The method of  claim 1 , comprising
 (i) applying inorganic material to a plurality of said solid cores   (ii) submitting the plurality of said solid cores to agitation,   (iii) repeating step (i) n times, wherein n is an integer of at least 1, and   (iv) when n is an integer of at least 2, repeating step (ii) after at least some of the steps (i).   
     
     
         4 . The method of  claim 3 , wherein n is an integer of at least 1 and at most 50. 
     
     
         5 . The method of  claim 4 , wherein n is an integer of at least 2 and at most 20. 
     
     
         6 . The method of  claim 5 , wherein n is an integer of at least 3 and at most 10. 
     
     
         7 . The method of  claim 1 , wherein said solid cores are submitted to continuous or intermittent agitation during the application of inorganic material. 
     
     
         8 . The method of  claim 1 , wherein said inorganic material is applied by atomic layer deposition, chemical vapour deposition or physical vapour deposition. 
     
     
         9 . The method of  claim 1 , wherein inorganic material comprises at least one metal or metalloid element. 
     
     
         10 . The method of  claim 9 , wherein the element that is a metal or metalloid is present as an oxide, a hydroxyoxide, a carbide, a selenide, a nitride, sulphide, fluoride, chloride and/or a salt. 
     
     
         11 . The method of  claim 10 , wherein the element is present as an oxide. 
     
     
         12 . The method of  claim 1 , wherein the inorganic material comprises aluminium oxide (Al 2 O 3 ), titanium dioxide (TiO 2 ), iron oxide (Fe x O y ), gallium oxide (Ga 2 O 3 ) and magnesium oxide (MgO), zinc oxide (ZnO), niobium oxide (Nb 2 O 5 ), hafnium oxide (HfO 2 ), tantalum oxide (Ta 2 O 5 ), lanthanum oxide (La 2 O 3 ), zirconium dioxide (ZrO 2 ) and/or silicon dioxide (SiO 2 ). 
     
     
         13 . The method of  claim 1 , wherein several layers of inorganic material are applied to the solid core. 
     
     
         14 . The method of  claim 13 , wherein layers of different composition are applied to the solid core. 
     
     
         15 . The method of  claim 1 , wherein the biologically active substance is a therapeutically active substance. 
     
     
         16 . The method of  claim 1 , comprising
 bringing a sample of the nanoparticles into contact with a liquid phase which is a solvent for the solid core and for the inorganic coating,   measuring dissolution of the coated nanoparticle solid cores in the liquid phase,   comparing the dissolution of coated nanoparticle solid cores with the dissolution of similar solid cores having no inorganic coating,   determining a delay in dissolution of the coated nanoparticle solid cores compared to the dissolution of similar solid cores having no inorganic coating, and   selecting coated nanoparticles having a delay in dissolution exceeding a predetermined length of time.   
     
     
         17 . The method of  claim 16 , wherein the delay in dissolution is determined as the difference between the time needed to dissolve at least 50% by weight of the coated nanoparticle solid cores and the time needed to dissolve at least 50% by weight of the solid cores having no coating. 
     
     
         18 . The method of  claim 17 , wherein the predetermined length of time is at least 5 minutes. 
     
     
         19 . The method of  claim 17 , wherein the predetermined length of time is at least 1 hour. 
     
     
         20 . A plurality of coated nanoparticles obtainable by a method according to  claim 1 . 
     
     
         21 . The plurality of coated nanoparticles according to  claim 20 , wherein the biologically active substance is a therapeutically active substance. 
     
     
         22 . A pharmaceutical composition comprising a plurality of coated nanoparticles according to  claim 21  and a pharmaceutically acceptable carrier. 
     
     
         23 . A method of preparing a pharmaceutical composition, comprising combining a plurality of nanoparticles according to  claim 22  and a pharmaceutically acceptable carrier or excipient.