02882naa a2200313 a 450000100080000000500110000800800410001902400520006010000190011224501670013126000090029852019040030765000130221165000170222465300160224165300270225765300170228465300210230170000180232270000210234070000190236170000230238070000160240370000170241970000250243670000220246170000240248377300610250721172062024-02-06 2019 bl uuuu u00u1 u #d7 ahttps://doi.org/10.1016/j.msec.2019.1100062DOI1 aARAƚJO, R. S. aCloxacillin benzathine-loaded polymeric nanocapsulesbPhysicochemical characterization, cell uptake, and intramammary antimicrobial effect.h[electronic resource] c2019 aThe present work shows the development and evaluation of the veterinary antibiotic cloxacillin benzathine(CLOXB) loaded into poly-ε-caprolactone (PCL) nanocapsules (NC), as a potential new treatment strategy tomanage bovine intramammary infections, such as mastitis.Staphylococcus aureus-induced mastitis is often arecurrent disease due to the persistence of bacteria within infected cells. CLOXB-PCL NC were prepared byinterfacial deposition of preformed biodegradable polymer followed by solvent displacement method. The meandiameter of NC varied from 241 to 428 nm and from 326 to 375 nm, when determined by dynamic light scat-tering and by atomic force microscopy, respectively. The zeta potential of NC was negative and varied from−28to−51 mV.In vitrorelease studies from the NC were performed in two media undersinkconditions: PBS with1% polyethylene glycol or milk. A reversed-phase HPLC method was developed to determine the NC entrapmentefficiency and kinetics of CLOXB release from the NC. Free CLOXB dissolution occurred very fast in both media,while drug release from the NC was slower and incomplete (below 50%) after 9 h. CLOXB release kinetics frompolymeric NC wasfitted with the Korsmeyer-Peppas model indicating that CLOXB release is governed by dif-fusion following Fick's law. Thefluorescence confocal microscopy images of macrophage-like J774A.1 cellsreveal NC uptake and internalizationin vitro. In addition, antimicrobial effect of the intramammary adminis-tration of CLOXB-PCL NC in cows with mastitis resulted in no clinical signs of toxicity and allowed completepathogen elimination after treatment. Thein vivoresults obtained in this work suggest that CLOXB-PCL NC couldbe a promising formulation for the treatment of intramammary infections in cattle, considering their physico-chemical properties, release profiles and effects on bovine mastitis control. aMastitis aNanocapsules aCell uptake aCloxacillin benzathine aIntramammary aRelease kinetics1 aGARCIA, G. M.1 aVILELA, J. M. C.1 aANDRADE, M. S.1 aOLIVEIRA, L. A. M.1 aKANO, E. K.1 aLANGE, C. C.1 aBRITO, M. A. V. P. E1 aBRANDAO, H. de M.1 aMOSQUEIRA, V. C. F. tMaterials Science & Engineering Cgv. 104, 110006, 2019.