Abstract
The encapsulation of drugs in nanoparticles serves as an effective way to modify pharmacokinetics and therapeutic efficacy. Nanoparticles comprised of poly(d,l-lactide-co-glycolide) (PLGA) are well suited for this purpose; they are accessible using multiple synthesis methods, are highly biocompatible and biodegradable, and possess desirable drug release properties. In the present study, we have explored the effects of various formulation parameters on the physical properties of PLGA nanoparticles synthesised using a microfluidic assisted nanoprecipitation method and loaded with a model drug. PLGA nanoparticles, with diameters ranging from 165–364nm, were produced using three alternate stabilisers; poly(vinyl alcohol) (PVA), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and didodecyldimethylammonium bromide (DMAB). Three additional formulations used PVA in addition to 20wt-% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), and oleic acid. Spectrophotometric analysis demonstrated that the use of PVA increased the loading efficiency over that of TPGS and DMAB formulations, while the inclusion of oleic acid in the PVA formulation resulted in a further 3-fold increase in loading efficiency. Invitro release studies demonstrate that the inclusion of lipid additives significantly alters release kinetics; release was most rapid and complete in the formulation containing oleic acid, while the addition of DOTAP and DOTMA significantly reduced release rates. Finally, the antimicrobial activity of each formulation was tested against Staphylococcus aureus and Bacillus cereus, with minimum inhibitory concentrations nearing or exceeding that of free rifampicin.
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