Nanoparticle targeted drug delivery to the lungs using extra-testicular sertoli cells

Abstract

A method of delivering a compound of interest to the lungs of a subject by the intravenous injection of Sertoli cells loaded with a plurality of chitosan nanoparticles coupled with the compound of interest is provided. Testis-derived rat Sertoli cells were pre-loaded with chitosan nanoparticles coupled with or without the drug curcumin, pre-labeled with a fluorescent cell marker and then injected intravenously into the control or asthmatic mouse model host. Intact pre-loaded, pre-labeled Sertoli cells were present in the lungs at 15 minutes post-injection, appeared entrapped in the pulmonary pre-capillary vascular bed around alveolar sacs but were not present one hour post-injection although Sertoli cell label and cellular debris was. Most of the injected nanoparticle load (70%) and curcumin load (80%) was present in the lungs 15 minutes post-injection, and remained at 70% and 80%, respectively, one hour post-injection.

1 . A method of delivery of a compound of interest to the lungs of a subject, comprising:
 providing a plurality of Sertoli cells;   coupling a plurality of chitosan nanoparticles with the compound of interest;   loading the Sertoli cells with the plurality of chitosan nanoparticles coupled to the compound of interest; and   injecting the loaded Sertoli cells intravenously into the subject.   
     
     
         2 . The method of  claim 1 , further comprising labeling the chitosan nanoparticles with a fluorescent marker. 
     
     
         3 . The method of  claim 1 , further comprising labeling the Sertoli cells with a fluorescent marker. 
     
     
         4 . The method of  claim 1 , wherein the compound of interest is a therapeutic agent. 
     
     
         5 . The method of  claim 4 , wherein the compound is curcumin. 
     
     
         6 . The method of  claim 4 , wherein the compound of interest is coupled to the chitosan nanoparticles, further comprising:
 dissolving the chitosan in acetic acid to form an acetic acid-chitosan solution;   adding tripolyphosphatesodium dropwise to the acetic acid-chitosan solution; and   stirring the acetic acid-chitosan solution.   
     
     
         7 . The method of  claim 1 , wherein the chitosan is 60 kDa chitosan. 
     
     
         8 . The method of  claim 1 , wherein the Sertoli cells are isolated from mammalian testes. 
     
     
         9 . The method of  claim 1 , wherein the Sertoli cells are xenogenic. 
     
     
         10 . The method of  claim 1 , wherein the step of loading the Sertoli cells with the plurality of chitosan nanoparticles coupled to the compound of interest further comprises:
 suspending the Sertoli cells in an incubation medium;   adding the plurality of chitosan nanoparticles coupled to the compound of interest; and   incubating the Sertoli cells in the incubation medium that comprises the chitosan nanoparticles coupled to the compound of interest.   
     
     
         11 . A compound comprising a plurality of Sertoli cells loaded with a plurality of chitosan nanoparticles. 
     
     
         12 - 16 . (canceled) 
     
     
         17 . The method of  claim 1 , wherein the subject is a human. 
     
     
         18 . The method of  claim 1 , wherein the Sertoli cells are human Sertoli cells. 
     
     
         19 . The method of  claim 17 , wherein the Sertoli cells are human Sertoli cells.