Compositions and methods for enhancing receptor-mediated cellular internalization

Abstract

Compositions and methods for improving cellular internalization of one or more compounds are disclosed. The compositions include a compound to be delivered and a biocompatible viscous material, such as a hydrogel, lipogel, or highly viscous sol. The composition also include, or are administered in conjunction with, an enhancer in an amount effective to maximize expression of or binding to receptors and enhance RME of the compound into the cells. This leads to high transport rates of compounds to be delivered across cell membranes, facilitating more efficient delivery of drugs and diagnostic agents. Compositions are applied topically orally, nasally, vaginally, rectally, and ocularly. The enhancer is administered with the composition or separately, either systemically or preferably locally. The compound to be delivered can also be the enhancer.

1 - 27 . (canceled)  
   
   
       28 . A dosage formulation for systemic delivery of an agent to an individual comprising 
 a viscous material and an agent to be delivered, wherein the viscous material comprises a polysaccharide in a concentration range of between 1.0 and 2.0% (w/w), a hydrogel, lipogel, or sol,    wherein the agent is selected from the group consisting of proteins, peptides, nucleotide molecules, saccharides, polysaccharides, lipids, synthetic chemotherapeutic agents, inorganic chemotherapeutic agent, organic chemotherapeutic agent, and diagnostic compounds, and is in a sufficient amount for systemic delivery to the individual, and    wherein the dosage formulation has an apparent viscosity of less than 10 Poise or greater than 2000 Poise at a shear stress of between approximately 1 and 200 Pascal.    
   
   
       29 . The dosage formulation of  claim 28 , wherein the polysaccharide is selected from the group consisting of celluloses, dextrans and alginates.  
   
   
       30 . The dosage formulation of  claim 29 , wherein the polysaccharide is methylcellulose.  
   
   
       31 . The dosage formulation of  claim 28 , wherein the concentration of the polysaccharide is less than or equal to 1.75% (w/w).  
   
   
       32 . The dosage formulation of  claim 28 , wherein the agent is selected from the group consisting of insulin, alpha interferons, beta interferon, follicle stimulating hormone, and growth factors.  
   
   
       33 . A dosage formulation for local delivery of an agent to an individual comprising 
 a viscous material and an agent to be delivered, wherein the viscous material comprises a polysaccharide in a concentration range of between 1.0 and 2.0% (w/w), a hydrogel, lipogel, or sol,    wherein the agent is selected from the group consisting of proteins, peptides, nucleotide molecules, saccharides, polysaccharides, lipids, synthetic chemotherapeutic agents, inorganic chemotherapeutic agent, organic chemotherapeutic agent, and diagnostic compounds, and is in a sufficient amount for local delivery to the individual, and    wherein the dosage formulation has an apparent viscosity of less than 10 Poise or greater than 2000 Poise at a shear stress of between approximately 1 and 200 Pascal.    
   
   
       34 . The dosage formulation of  claim 33 , wherein the polysaccharide is selected from the group consisting of celluloses, dextrans and alginates.  
   
   
       35 . The dosage formulation of  claim 34 , wherein the polysaccharide is methylcellulose.  
   
   
       36 . The dosage formulation of  claim 33 , wherein the concentration of the polysaccharide is less than or equal to 1.75% (w/w).  
   
   
       37 . The dosage formulation of  claim 33 , wherein the agent is selected from the group consisting of insulin, alpha interferons, beta interferon, follicle stimulating hormone, and growth factors.  
   
   
       38 . The dosage formulation of  claim 33  wherein the agent is gonadotropin releasing hormone (“GnRH”) or its analog.  
   
   
       39 . A method for delivering an agent to an individual comprising administering to the individual a dosage formulation comprising 
 (a) a viscous material comprising a polysaccharide in a concentration range of between 1.0 and 2.0% (w/w), a hydrogel, lipogel, or sol and    (b) the agent to be delivered, wherein the agent is selected from the group consisting of proteins, peptides, nucleotide molecules, saccharides, polysaccharides, lipids, synthetic chemotherapeutic agents, inorganic chemotherapeutic agent, organic chemotherapeutic agent, and diagnostic compounds, and is in a sufficient amount for systemic delivery or local delivery to the individual,    wherein the dosage formulation has an apparent viscosity of less than 10 Poise or greater than 2000 Poise at a shear stress of between approximately 1 and 200 Pascal.    
   
   
       40 . The method of  claim 39 , wherein the polysaccharide is selected from the group consisting of celluloses, dextrans and alginates.  
   
   
       41 . The method of  claim 39 , wherein the polysaccharide is methylcellulose.  
   
   
       42 . The method of  claim 39 , wherein the agent is delivered systemically.  
   
   
       43 . The method of  claim 39 , wherein the agent is delivered locally.  
   
   
       44 . The method of  claim 39 , wherein the dosage formulation is administered orally, nasally, vaginally, rectally, or ocularly.  
   
   
       45 . The method of  claim 39 , wherein the dosage formulation is administered topically.  
   
   
       46 . The method of  claim 39 , wherein the agent is delivered to mucosal tissue.  
   
   
       47 . The method of  claim 39 , wherein the agent is delivered to lower gastrointestinal tract mucosal tissue.  
   
   
       48 . The method of  claim 39 , wherein the agent is delivered to the vagina or rectum.  
   
   
       49 . The method of  claim 39 , wherein the agent is delivered to the eye.  
   
   
       50 . The method of  claim 39 , wherein the agent is delivered to the respiratory or pulmonary system.  
   
   
       51 . The method of  claim 39  wherein the agent is delivery nasally.