Swellable particles for drug delivery

Abstract

Swellable particles for delivering a working agent to the pulmonary system comprise a plurality of biodegradable particles each formed from a polymer network, each of the plurality of biodegradable particles having a mass mean aerodynamic diameter not exceeding 5 μm, the particles being swellable by hydration to a size that is greater than 6 μm volume mean diameter, and a working agent entrapped in the polymer network of each of the plurality of biodegradable particles.

1 . Swellable particles for delivering a working agent to the pulmonary system, the particles comprising:
 a plurality of biodegradable particles each formed from a polymer network, each of the plurality of biodegradable particles having a mass median aerodynamic diameter not exceeding 5 μm, the particles being swellable by hydration to a size that is greater than 6 μm volume mean diameter; and   a working agent entrapped in the polymer network of each of the plurality of biodegradable particles.   
     
     
         2 - 3 . (canceled) 
     
     
         4 . The particles of  claim 1 , wherein the working agent is entrapped in nanoparticles, wherein the nanoparticles are incorporated in the biodegradable particles. 
     
     
         5 . The particles of  claim 1 , wherein the working agent is chemically bonded with the polymer network of the biodegradable particle. 
     
     
         6 . The particles of  claim 1 , wherein the working agent comprises one or more of a therapeutic treating agent, a diagnostic agent, a prophylactic agent, or an imaging agent. 
     
     
         7 . The particles of  claim 6 , wherein the working agent comprises a mucolytic agent. 
     
     
         8 . The particles of  claim 1 , wherein the working agent comprises at least one of an antibiotic agent, a cytotoxic agent, an RNA interfering agent, and a gene. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . The particles of  claim 1 , wherein the working agent comprises multiple cytotoxic agents. 
     
     
         13 . The particles of  claim 1 , wherein the working agent comprises a cytotoxic agent and an RNA interfering agent. 
     
     
         14 . The particles of  claim 1 , wherein at least 90% of the particles have an aerodynamic diameter of 5 μm or less and swell to a size greater than 6 μm volume mean diameter. 
     
     
         15 . The particles of  claim 1 , wherein the polymer network of the biodegradable particles comprises a material selected from the group consisting of a biodegradable natural polymer, a synthetic polymer, a protein, and a carbohydrate, or combinations thereof. 
     
     
         16 . The particles of  claim 1 , wherein the plurality of biodegradable particles comprise hydrogel particles. 
     
     
         17 . The particles of  claim 1 , including a coating on the plurality of biodegradable particles that controls a rate of particle swelling. 
     
     
         18 . The particles of  claim 17 , wherein the coating comprises an excipient selected from the group consisting of a carbohydrate, a lipid, a protein, or a biocompatible salt of sodium, potassium, calcium, magnesium or lithium. 
     
     
         19 . The particles of  claim 17 , wherein the coating comprises a targeting agent for binding to receptors or to a target within a diseased site. 
     
     
         20 . An aerosol comprising the swellable particles of  claim 1 . 
     
     
         21 . The particles of  claim 1 , wherein the polymer network of each of the plurality of biodegradable particles comprises a cross-linked polymer network. 
     
     
         22 . The particles of  claim 21 , wherein the cross-linked polymer network physically entraps the working agent in the polymer network. 
     
     
         23 . The particles of  claim 21 , further comprising a crosslinker to form crosslinking of polymers within the polymer network. 
     
     
         24 . The particles of  claim 23 , wherein the crosslinker comprises dithiothreitol,