Enhancing encapsulation efficiency of highly water-soluble antibiotic in poly(lactic-co-glycolic acid) nanoparticles: Modifications of standard nanoparticle preparation methods

Effective encapsulations of drugs that are highly soluble in both water and organic solvents are notoriously difficult to achieve using standard nanoparticle preparation methods, such as nanoprecipitation (NPC), single (ESE), and double (DESE) emulsification-solvent-evaporation methods. Modifications of the standard preparation methods are therefore needed to enhance encapsulation efficiency of this group of drugs. The present work investigates the feasibility of enhancing the encapsulation efficiency of highly water and solvent-soluble levofloxacin, which is widely used in antibiotic therapy against pulmonary biofilm infections, into poly(lactic-co-glycolic acid) (i.e. PLGA) nanoparticles. In addition, the nanoparticles are evaluated in terms of their drug loading, size, production yield, and in-vitro drug release profile. Lecithin inclusion into the aqueous phase in the ESE method results in two-fold improvements in the encapsulation efficiency and drug loading (i.e. 23% and 2.3%, w/w, respectively) compared to the standard method. Similar results are obtained when the water-miscibility level of the oil phase is increased in the DESE method. Importantly, these nanoparticles possess size ≈200-300. nm and biphasic extended drug release profiles suitable for anti-biofilm therapy. Lastly, the nanoparticles can be readily transformed into inhalable solid dosage forms without jeopardizing their drug loadings and antibacterial activities.