Engineered biocompatible antibiotic particles and their use against urinary tract infection

A method of preventing or reducing severity of a urinary tract infection in a subject in need thereof, the method comprising:

• administering a therapeutically effective amount of a plurality of particles, wherein each particle of the plurality comprises:
• a biocompatible matrix comprising:
• poly(D,L-lactide-co-glycolide),
• a cationic agent and/or a pharmaceutically acceptable salt thereof;
• and
• an antibiotic and/or pharmaceutically acceptable salt thereof, wherein the antibiotic is dispersed substantially throughout the biocompatible matrix;
• and
• a non-spherical three-dimensional engineered shape comprising:
• at least two substantially planar surfaces, and
• in cross-section, a maximum dimension of less than about 10 μm;
• wherein administration provides protection to the urinary bladder from 104 kanamycin resistance-marked E. coli UTI189 for at least eight hours.

A method of preventing or reducing severity of a urinary tract infection in a subject in need thereof, the method comprising:

• administering a therapeutically effective amount of a plurality of particles, wherein each particle of the plurality comprises:
• a biocompatible matrix comprising:
• poly(D,L-lactide-co-glycolide) comprising a molecular weight average (Mw) of about 16 kDa to about 54 kDa,
• 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and/or a pharmaceutically acceptable salt thereof, wherein a pre-particle solution used to fabricate the particle comprises about 0 wt % to about 5 wt % DOTAP;
• and
• levofloxacin and/or pharmaceutically acceptable salt thereof, wherein:
• levofloxacin comprises about 3.5 wt % to about 13.5 wt % of the particle and
• the antibiotic is dispersed substantially throughout the biocompatible matrix;
• and
• a non-spherical three-dimensional engineered shape comprising:
• at least two substantially planar surfaces, and
• in cross-section, a maximum dimension of less than about 10 μm;
• and
• wherein administration provides protection to the urinary bladder from 104 kanamycin resistance-marked E. coli UTI189 for at least eight hours.

A method of preventing or reducing severity of a urinary tract infection in a subject in need thereof, the method comprising:

• administering a therapeutically effective amount of a plurality of particles, wherein each particle of the plurality comprises:
• a biocompatible matrix comprising:
• a biocompatible polymer,
• a cationic agent and/or a pharmaceutically acceptable salt thereof;
• and
• an antibiotic and/or pharmaceutically acceptable salt thereof, wherein the antibiotic is dispersed substantially throughout the biocompatible matrix;
• and
• a non-spherical three-dimensional engineered shape comprising:
• at least two substantially planar surfaces, and
• in cross-section, a maximum dimension of less than about 10 μm;
• wherein administration reduces severity of urinary bladder infection up to 58 percent at eighteen hours post-administration.