Sustained Antibacterial Activity of Doxycycline-Loaded Poly( D , L -Lactide-Co-Glycolide) and Poly(ε-Caprolactone) Nanoparticles

Abstract

To increase the entrapment efficiency of doxycycline (DXY)-loaded poly(D,L-lactide-co-glycolide) (PLGA):poly(epsilon-caprolactone) (PCL) nanoparticles by up to 70% by varying the different formulation parameters such as polymer ratio, amount of drug loading (w/w), solvent selection, electrolyte addition and pH in the formulation. Biodegradable polymers PLGA and PCL are used in various ratios for nanoparticle preparation using the water-in-oil-in-water double emulsion technique for water-soluble DXY. The physicochemical characterization of nanoparticles included size and surface charge measurement, study of surface morphology using scanning-electron microscopy, Fourier transform infrared spectroscopy study, differential scanning calorimetry analysis and in vitro release kinetics study. The mean particle size ranged from 230 to 360 nm, as measured by dynamic laser light scattering, and scanning-electron microscopy confirmed the spherical nature and smooth surface of the nanoparticles. Fourier transform infrared spectroscopy analysis of void nanoparticles, drug-loaded nanoparticles and native DXY indicated no interaction between the drug and polymer in the nanoparticle. Differential scanning calorimetry analysis of drug-loaded nanoparticles indicated a molecular level dispersion of DXY in the formulation. The antibacterial activity of native DXY and DXY-loaded nanoparticles were tested using a strain of Escherichia coli (DH5alpha) through growth inhibition and colony-counting method. The results indicated that DXY-loaded nanoparticles are more effective than native DXY due to the sustained release of DXY from nanoparticles in the E. coli strain.