Micro vs. nano: PLGA particles loaded with trimethoprim for instillative treatment of urinary tract infections

Recurring infections and increasing resistances continue to complicate treatment of urinary tract infections. To investigate alternative treatment options, trimethoprim loaded micro- (D[4;3] of 1-9 mu m) and nanoparticles (Z-Avg of 200-400 nm) were prepared from two types of poly(D,L-lactic-co-glycolic acid) (PLGA) for instillative therapy. While PLGA 503H microparticles could not be loaded with more than 2.6% trimethoprim, PLGA 2300 entrapped 22%. When preparing nanoparticles, both types displayed an even higher drug load of up to 29% using PLGA 2300, while PLGA 503H drug load stagnated at 10%. After eight hours, drug release from microparticles amounted to 55% (503H) and 35% (2300) whereas total drug release occurred after 8 (503H) and 9 days (2300). In case of nanoparticles, trimethoprim was liberated much faster with 60% after 2 h and a complete release after 24 h from both polymers. PLGA 2300 seems to be the better choice for entrapment of trimethoprim in microparticles considering the drug load. Both polymers, however, seem to be viable options for nanoparticles. Due to the higher overall drug load, nanoparticles seem to be advantageous over microparticles for instillative therapy, especially when prepared with PLGA 2300.