Nanoparticle film delivery systems

Abstract

A therapeutic or bioeffecting film delivery system which includes nanoparticles having actives bound to or associated with the nanoparticles and which when administered allow the active to perform a therapeutic or bioeffecting function.

1 . A therapeutic or bioaffecting film delivery system comprising:
 (a) one or more film matrices comprising at least one polymer;   (b) a plurality of nanoparticles incorporated in at least one of said film matrices, said nanoparticles comprising:
 (i) a core comprising a metal; 
 (ii) a corona comprising a plurality of ligands covalently linked to the core, wherein at least one of said ligands comprises a carbohydrate moiety; and 
 (iii) at least one peptide bound to the corona. 
   
     
     
         2 - 6 . (canceled) 
     
     
         7 . The film delivery system according to  claim 1 , wherein the peptide is selected from the group consisting of: insulin, GLP-1, IGF1, IGF2, relaxin, INSL5, INSL6, INSL7, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PTT), neuropeptide Y, oxytocin, vasopressin, GnRH, TRH, CRH, GHRH/somatostatin, FSH, LH, TSH, CGA, prolactin, ClIP, ACTH, MSH, enorphins, lipotropin, GH, calcitonin, PTH, inhibin, relaxin, hCG, HPL, glucagons, insulin, somatostatin, melatonin, thymosin, thmulin, gastrin, ghrelin, thymopoietin, CCK, GIP secretin, motin VIP, enteroglucagon, IGF-1, IGF-2, leptin, adiponectin, resistin Osteocalcin, renin, EPO, calicitrol, ANP, BNP, chemokines, cytokines, adipokines and biologically active analogs thereof. 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The film delivery system according to  claim 1 , wherein the carbohydrate moiety comprises a glycoside of galactose, glucose, glucosamine, N-acetylglucosamine, mannose, fucose and/or lactose. 
     
     
         12 . The film delivery system according to  claim 11 , wherein the carbohydrate moiety comprises a galactopyranoside and/or a glucopyranoside. 
     
     
         13 . The film delivery system according to  claim 1 , wherein the carbohydrate moiety is covalently linked to the core via a linker selected from the group consisting of: sulphur-containing linkers, amino-containing linkers, phosphate-containing linkers and oxygen-containing linkers. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . The film delivery system according to  claim 1 , wherein said plurality of ligands covalently linked to the core further comprises at least one non-carbohydrate ligand. 
     
     
         17 . The film delivery system according to  claim 16 , wherein said at least one non-carbohydrate ligand comprises an amine group. 
     
     
         18 . The film delivery system according to  claim 17 , wherein said at least one non-carbohydrate ligand comprises 1-amino-17-mercapto-3,6,9,12,15-pentaoxa-heptadecanol covalently linked to the core via the thiol sulphur. 
     
     
         19 - 23 . (canceled) 
     
     
         24 . The film delivery system according to  claim 1 , wherein the corona comprises 44-106 ligands per core. 
     
     
         25 . The film delivery system according to  claim 1 , wherein at least 5 or more peptide molecules are bound per core. 
     
     
         26 . The film delivery system according to  claim 1 , wherein the core comprises a metal selected from the group consisting of: Au, Ag, Cu, Pt, Pd, Fe, Co, Gd, Zn or any combination thereof. 
     
     
         27 - 35 . (canceled) 
     
     
         36 . The film delivery system according to  claim 1 , wherein the nanoparticle cores have an average diameter in the range of about 1 nm to about 10 nm. 
     
     
         37 - 46 . (canceled) 
     
     
         47 . The film delivery system according to  claim 1 , wherein the one or more film matrices are formed by evaporating a solvent carrier from the matrices to form a visco-elastic film within the first 10 minutes of applying heat or irradiation energy whereby the nanoparticles are locked in or substantially prevented from migrating within the matrices to provide a film delivery system with a uniform distribution of the nanoparticles. 
     
     
         48 . The film delivery system according to  claim 1 , wherein the one or more film matrices comprise two film layers having different release properties. 
     
     
         49 . The film delivery system according to  claim 1 , wherein the one or more film matrices comprise at least one water soluble or water swellable polymer. 
     
     
         50 - 55 . (canceled) 
     
     
         56 . The film delivery system according to  claim 1 , wherein the nanoparticles are uniformly distributed within the at least one or more film matrices. 
     
     
         57 . (canceled) 
     
     
         58 . The film delivery system according to  claim 1 , where in the total water content is about 10% or less by weight of the delivery system. 
     
     
         59 . The film delivery system according to  claim 1 , wherein the nanoparticles are incorporated or deposited on the surface of the one or more film matrices. 
     
     
         60 . The film delivery system according to  claim 1 , further comprising a permeation and/or penetration enhancing agent. 
     
     
         61 - 64 . (canceled) 
     
     
         65 . An insulin-containing film delivery system comprising:
 (a) one or more film matrices comprising at least one polymer;   (b) a plurality of nanoparticles incorporated in at least one of said film matrices, said nanoparticles comprising:
 (i) a core comprising a gold; 
 (ii) a plurality of ligands covalently attached to the core and forming a corona around the core, wherein the ligands comprise 2′-thioethyl-α-D-galactopyranoside and 1-amino-17-mercapto-3,6,9,12,15-pentaoxa-heptadecanol each bonded to the core via their respective sulphur atoms, and wherein the nanoparticles have an average of at least five insulin monomers bound per nanoparticle core. 
   
     
     
         66 . A process for making a film having a substantially uniform distribution of components, comprising the steps of:
 (a) forming a flowable polymer matrix comprising a water-soluble or water swellable polymer, a solvent and an active-carrying component, said active-carrying component comprising a plurality of nanoparticles comprising:
 (i) a core comprising a metal; 
 (ii) a corona comprising a plurality of ligands covalently linked to the core, wherein at least one of said ligands comprises a carbohydrate moiety; and 
 (iii) a peptide bound to the corona; 
   
       said matrix having a uniform distribution of said active;
 (b) casting said flowable polymer matrix; 
 (c) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said uniform distribution of said active by locking-in or substantially preventing migration of said active within said visco-elastic film; and 
 (d) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said uniform distribution of active by said locking-in or substantially preventing migration of said active is maintained. 
 
     
     
         67 . The process according to  claim 66 , wherein the visco-elastic film forms within about 4 minutes. 
     
     
         68 . The process of  claim 66 , further including the step of forming a second layer of film disposed thereover. 
     
     
         69 . A process for making a film having a substantially uniform distribution of components, comprising the steps of:
 (a) forming a masterbatch pre-mix comprising a solvent and a polymer selected from the group consisting of water-soluble polymers, water-swellable polymers and combinations thereof;   (b) adding an active-carrying component to a pre-determined amount of said masterbatch pre-mix to form a flowable polymer matrix, said active-carrying component comprising a plurality of nanoparticles comprising:
 (i) a core comprising a metal; 
 (ii) a corona comprising a plurality of ligands covalently linked to the core, wherein at least one of said ligands comprises a carbohydrate moiety; and 
 (iii) a peptide bound to the corona; said matrix having a uniform distribution of said active; 
   (c) casting said flowable polymer matrix;   (d) evaporating at least a portion of said solvent from said flowable polymer matrix to form a visco-elastic film within about 10 minutes or fewer to maintain said uniform distribution of said active-carrying component by locking-in or substantially preventing migration of said active within said visco-elastic film; and   (e) forming a resulting film from said visco-elastic film, wherein said resulting film has a water content of 10% or less and said uniform distribution of active-carrying component by said locking-in or substantially preventing migration of said active-carrying component is maintained.   
     
     
         70 . A method of lowering blood glucose in a mammalian subject in need thereof, comprising administering a therapeutically effective amount of a film delivery system as defined in  claim 1 . 
     
     
         71 . A method of treating diabetes in a mammalian subject in need thereof, comprising administering a therapeutically effective amount of a film delivery system as defined in  claim 1 . 
     
     
         72 . The method according to  claim 71 , wherein the method comprises or further comprises administration of the film delivery system to the subject via a mucosal or organ tissue surface or membrane. 
     
     
         73 - 76 . (canceled) 
     
     
         77 . Use of film delivery system as defined in  claim 1  in the preparation of a medicament, wherein the peptide wherein the peptide is monomeric and/or dimeric human insulin and wherein the method is for either lowering blood glucose in a mammalian subject in need thereof or treating diabetes in a mammalian subject in need thereof. 
     
     
         78 . An article of manufacture comprising at least one film comprising:
 (a) one or more film matrices comprising at least one polymer;   (b) a plurality of nanoparticles incorporated in at least one of said film matrices, said nanoparticles comprising:
 (i) a core comprising a metal; 
 (ii) a corona comprising a plurality of ligands covalently linked to the core, wherein at least one of said ligands comprises a carbohydrate moiety; and 
 (iii) a peptide bound to the corona; and 
   said at least one film has a water content of about 10% or less by weight of the at least one film and wherein when said at least one film is divided into individual dosage units, each dosage unit has an appropriate amount of peptide for administration and the amount of peptide in each dosage unit does not vary more than 10% from said appropriate amount.   
     
     
         79 . The article of manufacture according to  claim 78 , further comprising a container for housing the at least one film. 
     
     
         80 . The article of manufacture according to  claim 79 , further comprising an insert and/or a label. 
     
     
         81 . An article of manufacture comprising:
 at least one film delivery system as defined in  claim 1 ;   a container for housing the at least one film delivery system of film; and   optionally, an insert and/or a label.   
     
     
         82 . The film delivery system according to  claim 1 , divided into individual dosage units, each dosage unit having an appropriate amount of peptide for administration, wherein the amount of peptide in each dosage unit does not vary more than 10% from said appropriate amount.