Biodegradable polymeric compositions, methods of preparation and uses thereof

Abstract

Disclosed herein compositions of polysaccharides chemically cross-linked by aromatic dialdehydes. The compositions may be in form of polymeric sheets for a variety of applications. Disclosed also nano-sized particles comprising the polysaccharide chemically cross-linked by aromatic dialdehydes. The nano-sized particles may further comprise lipids and surfactants. Intranasal delivery of the nano-sized particles enables delivery of biologically active agents into the brain. Topical and transdermal delivery of the nano-sized particles enables delivery of biologically active agents for treatment of systemic or dermatological disorders. Methods of manufacturing and uses of the compositions are also disclosed.

1 - 34 . (canceled) 
     
     
         35 . A composition of matter comprising a polysaccharide chemically crosslinked by an aromatic dialdehyde. 
     
     
         36 . The composition of  claim 35 , wherein said aromatic dialdehyde is selected from the group consisting of divanillin, di-cinnamaldehyde, di-coniferylaldehyde, di-coumaraldehyde, and di-sinapaldehyde. 
     
     
         37 . The composition of  claim 35 , wherein said polysaccharide is a starch, an alginic acid, or hydroxypropyl cellulose. 
     
     
         38 . The composition of  claim 35 , in the form of a polymeric sheet, or a polymeric particle/capsule. 
     
     
         39 . The composition of  claim 35 , which is a pharmaceutically acceptable formulation. 
     
     
         40 . The composition of  claim 35 , in the form of nano-sized particles. 
     
     
         41 . The composition of  claim 40 , further comprising a bioactive material. 
     
     
         42 . The composition of  claim 41 , wherein the bioactive material is a naturally occurring substance, an antibiotic, or a CNS-active drug. 
     
     
         43 . The composition of  claim 35 , wherein the bioactive material is curcumin or a cannabinoid. 
     
     
         44 . The composition of  claim 35 , wherein the bioactive material is an antiemetic. 
     
     
         45 . The composition of  claim 35 , wherein the bioactive material is a peptide, polypeptide, glycoprotein, or oligonucleotide. 
     
     
         46 . The composition of  claim 35 , wherein the bioactive material is insulin 
     
     
         47 . The composition of  claim 35 , further comprising a lipid and/or a surfactant and/or a cosolvent. 
     
     
         48 . A process for manufacturing a polymeric composition, comprising combining in an aqueous medium a polysaccharide and an aromatic dialdehyde. 
     
     
         49 . The process according to  claim 48 , comprising the following steps:
 i) evaporating a solvent from a solution or an emulsion comprising said polysaccharide and said aromatic dialdehyde,   ii) spray-drying a solution or an emulsion comprising said polysaccharide and said aromatic dialdehyde,   iii) forming nano-sized particles comprising said polysaccharide and said aromatic dialdehyde by adding an anti-solvent [i.e. nanoprecipitation];   iv) separating nano-sized particles comprising said polysaccharide and said aromatic dialdehyde by adding a salt [i.e. salting-out], or   v) providing a microemulsion or a nanoemulsion comprising said polysaccharide and/or said aromatic dialdehyde.   
     
     
         50 . A method of treatment of a subject in need thereof, comprising administering to said subject a composition as claimed in claim  1  comprising a therapeutically effective amount of a bioactive agent. 
     
     
         51 . The method of  claim 50 , wherein the bioactive agent is an agent having an activity in the central nervous system. 
     
     
         52 . The method of  claim 50 , wherein the administration is intranasal administration. 
     
     
         53 . The method of  claim 50 , wherein following the administration to a test non-human mammal a concentration in the brain of said test non-human mammal is at least 150 percent higher than the concentration in the brain obtained following an intravenous or subcutaneous administration to a reference test non-human mammal. 
     
     
         54 . The method of  claim 50 , wherein the administration is transdermal administration, oral administration, sublingual administration, intrauterine administration, implanting devices, or parenteral administration.