Composition 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. A composition comprising
 (i) a carrier selected from the group consisting of viruses, liposomes, lipid/DNA complexes, micelles, protein/lipid complexes, nanoparticles, and microparticles,  
 wherein the carrier comprises a hormone targeting the carder  carrier to tissue expressing a receptor for the hormone, and  
 (ii) a viscous material selected from the group consisting of hydrogels, lipogels and sols,  
 wherein the viscous material alters cellular uptake of the carrier,  
 wherein the viscous material has an apparent viscosity between 0.1 and  2000  2 and 200  Poise at a sheer stress of between 1 and 1000 Pascal and at a strain rate approximately that of endocytosis, and  
 wherein the apparent viscosity is approximately equal to the viscosity of the cytosolic fluid in the cell to which the hormone is to be delivered.  
 
     
     
       2. The composition of  claim 1 , wherein the carrier further comprises an active agent. 
     
     
       3. The composition of  claim 1 , wherein the tissue is mucosal tissue. 
     
     
       4. The composition of  claim 3 , wherein the tissue is lower gastrointestinal tract mucosal tissue. 
     
     
       5. The composition of  claim 1 , wherein the hormone is GnRH or an analog of GnRH. 
     
     
       6. The composition of  claim 2 , wherein the active agent is selected from the group consisting of proteins, peptides, nucleotide molecules, saccharides, polysaccharides, lipids, synthetic organic and inorganic molecules, synthetic chemotherapeutic agents, and diagnostic compounds. 
     
     
       7. The composition of  claim 1 , wherein the composition is in a form suitable for administration to the vagina or rectum. 
     
     
       8. The composition of  claim 1 , wherein the composition is in a form suitable for administration to the nose, eye, or mouth. 
     
     
       9. The composition of  claim 1 , wherein the composition is in a form suitable for administration to the respiratory or pulmonary system. 
     
     
       10. The composition of  claim 1 , wherein the composition is in a form suitable for oral administration. 
     
     
       11. The composition of  claim 1 , wherein the composition is in a form suitable for parenteral or systemic administration. 
     
     
       12. The composition of  claim 1 , wherein the viscous material is a hydrogel. 
     
     
       13. The composition of  claim 12 , wherein the hydrogel comprises methyl cellulose. 
     
     
       14. The composition of  claim 1 , wherein the viscous material increases the rate of cellular internalization for the carrier. 
     
     
       15. The composition of  claim 1 , wherein the carrier is a microparticle or nanoparticle. 
     
     
       16. The composition of  claim 5 , wherein the viscous material comprises methyl cellulose. 
     
     
       17. The composition of  claim 16 , wherein the methyl cellulose concentration ranges from  1  to  2 % ( w/w ). 
     
     
       18. The composition of  claim 1 , wherein the hormone is a reproductive hormone.