Methods of making and using nanoparticles for treatment of bacterial biofilm

1 . A method of treating a bacterial infection within a subject in need thereof, wherein the bacterial infection is characterized by a bacterial biofilm comprising

administering to the subject a nanoparticle comprising

(1) a core comprising gelatin and an antibiotic,

(2) an inner first layer comprising chitosan surrounding the core and

(3) an outer layer comprising hyaluronic acid surrounding the inner first layer at least one layer surrounding the core,

wherein, after administration, the nanoparticle contacts the bacterial biofilm,

wherein the hyaluronic acid is responsive to hyaluronidase in the bacterial biofilm which degrades the hyaluronic acid to expose the chitosan,

wherein the chitosan is responsive to the pH of the bacterial biofilm, which swells the chitosan thereby allowing gelatinase in the bacterial biofilm to contact the gelatin, and

wherein gelatinase in the bacterial biofilm degrades the gelatin of the core to release the antibiotic, to kill the bacteria.

2 . The method of claim 1 wherein the bacterial infection is reduced, inhibited or eradicated.

3 . The method of claim 1 wherein the nanoparticle is within a pharmaceutical composition comprising a pharmaceutically acceptable excipient.

4 . A method of delivering an antibacterial to a bacterial infection within a subject in need thereof, wherein the bacterial infection is characterized by a bacterial biofilm comprising

administering to the subject a pharmaceutical composition comprising a nanoparticle in a pharmaceutically acceptable carrier, wherein the nanoparticle comprises

(1) a core comprising gelatin and an antibacterial,

(2) an inner first layer comprising chitosan surrounding the core and

(3) an outer layer comprising hyaluronic acid surrounding the inner first layer at least one layer surrounding the core,

wherein, after administration, the nanoparticle contacts the bacterial biofilm,

wherein the hyaluronic acid is responsive to hyaluronidase in the bacterial biofilm which degrades the hyaluronic acid to reveal the chitosan,

wherein the chitosan is responsive to the pH of the bacterial biofilm which swells the chitosan thereby allowing gelatinase in the bacterial biofilm to contact the gelatin, and

wherein gelatinase in the bacterial biofilm degrades the gelatin of the core to release the antibacterial, such that the antibacterial contacts bacteria within the bacterial biofilm.

5 . The method of claim 4 wherein the bacterial infection is reduced, inhibited or eradicated.

6 . A method of treating a bacterial biofilm within an individual in need thereof comprising

administering to the subject a nanoparticle comprising

(1) a core comprising gelatin and an antibiotic

(2) an inner first layer comprising chitosan surrounding the core, and

(3) an outer layer comprising hyaluronic acid surrounding the inner layer

wherein, after administration, the nanoparticle contacts the bacterial biofilm,

wherein the hyaluronic acid is responsive to hyaluronidase in the bacterial biofilm which degrades the hyaluronic acid revealing the inner first layer comprising chitosan,

wherein the chitosan is responsive to the pH of the bacterial biofilm which swells the chitosan thereby allowing gelatinase in the bacterial biofilm to contact the gelatin, and

wherein the gelatinase in the bacterial biofilm degrades the gelatin of the core to release the antibiotic, thereby treating the bacterial biofilm.

7 . The method of claim 6 wherein the nanoparticle is within a pharmaceutical composition comprising a pharmaceutically acceptable excipient.