Effects of Antibiotic Physicochemical Properties on Their Release Kinetics from Biodegradable Polymer Microparticles

Purpose: This study investigated the effects of the physicochemical properties of antibiotics on the morphology, loading efficiency, size, release kinetics, and antibiotic efficacy of loaded poly(DL-lactic-co-glycolic acid) (PLGA) microparticles (MPs) at different loading percentages. Methods: Cefazolin, ciprofloxacin, clindamycin, colistin, doxycycline, and vancomycin were loaded at 10 and 20 wt% into PLGA MPs using a water-in-oil-in water double emulsion fabrication protocol. Microparticle morphology, size, loading efficiency, release kinetics, and antibiotic efficacy were assessed. Results: The results from this study demonstrate that the chemical nature of loaded antibiotics, especially charge and molecular weight, influence the incorporation into and release of antibiotics from PLGA MPs. Drugs with molecular weights less than 600 Da displayed biphasic release while those with molecular weights greater than 1,000 Da displayed triphasic release kinetics. Large molecular weight drugs also had a longer delay before release than smaller molecular weight drugs. The negatively charged antibiotic cefazolin had lower loading efficiency than positively charged antibiotics. Microparticle size appeared to be mainly controlled by fabrication parameters, and partition and solubility coefficients did not appear to have an obvious effect on loading efficiency or release. Released antibiotics maintained their efficacy against susceptible strains over the duration of release. Duration of release varied between 17 and 49 days based on the type of antibiotic loaded. Conclusions: The data from this study indicate that the chemical nature of antibiotics affects properties of antibiotic-loaded PLGA MPs and allows for general prediction of loading and release kinetics

Direct visualisation of lipid bilayer cubic phases using Atomic Force Microscopy

Inverse bicontinuous cubic (Q(II)) phases are nanostructured materials formed by lipid self-assembly. We have successfully imaged thin films of hydrated Q(II) phases from two different systems using AFM. The images show periodic arrays of water channels with spacing and symmetry consistent with published SAXS data on the bulk materials

Imaging of poly(α-hydroxy-ester) scaffolds with X-ray phase-contrast microcomputed tomography

Porous scaffolds based on poly(α-hydroxy-esters) are under investigation in many tissue engineering applications. A biological response to these materials is driven, in part, by their three-dimensional (3D) structure. The ability to evaluate quantitatively the material structure in tissue-engineering applications is important for the continued development of these polymer-based approaches. X-ray imaging techniques based on phase contrast (PC) have shown a tremendous promise for a number of biomedical applications owing to their ability to provide a contrast based on alternative X-ray properties (refraction and scatter) in addition to X-ray absorption. In this research, poly(α-hydroxy-ester) scaffolds were synthesized and imaged by X-ray PC microcomputed tomography. The 3D images depicting the X-ray attenuation and phase-shifting properties were reconstructed from the measurement data. The scaffold structure could be imaged by X-ray PC in both cell culture conditions and within the tissue. The 3D images allowed for quantification of scaffold properties and automatic segmentation of scaffolds from the surrounding hard and soft tissues. These results provide evidence of the significant potential of techniques based on X-ray PC for imaging polymer scaffolds

Controllable Internal Mixing in Coalescing Droplets Induced by The Solutal Marangoni Convection of Surfactants with Distinct Headgroup Architectures

Through several complementary experiments, an investigation of the bulk and interfacial flows that emerged during the coalescence of two water-in-oil droplets with asymmetric compositional properties was performed. By adding surfactant to one of the coalescing droplets and leaving the other surfactant-free, a strong interfacial tension gradient (i.e., solutal Marangoni) driving energy between the merging droplets generated pronounced internal mixing. The contributions of two distinct types of surfactant, anionic ammonium lauryl sulfate (ALS) and cationic cetyltrimethylammonium bromide (CTAB) on the rate of coalescence bridge expansion and on the generation of opposing flows during coalescence were investigated. All coalescence experiments supported the power law relation between the radius of the expanding connective liquid bridge and time, rb ∝ t1/2. However, the presence of surfactant decreased the magnitude of the prefactor in this relationship due to induced interfacial solutal Marangoni convection. Experiments showed that packing efficiency, diffusivity, and bulk concentration of the selected surfactant are vital in solutal Marangoni convection and thus the degree and timescale of internal mixing between merging droplets, which has yet to be adequately discussed within the literature. Denser interfacial packing efficiency and lower diffusivity of CTAB produced stronger opposing bulk and interfacial flow as well as greater bulk mixing. A discussion of how optimized surfactant selection and solutal Marangoni convection can be used for passively inducing convective mixing between coalescing drops in microfluidic channels when viscosity modulation is not feasible is provided