Liposomes are attractive vehicles for localized delivery of antibiotics. There exists, however, a gap in knowledge when it comes to achieving high liposomal loading efficiencies for antibiotics. To address this issue, we investigated three antibiotics of clinical relevance against staphylococcal infections with different hydrophilicity and chemical structure, namely, vancomycin hydrochloride, teicoplanin, and rifampin. We categorized the suitability of different encapsulation techniques on the basis of encapsulation efficiency, lipid requirement (important for avoiding lipid toxicity), and mass yield (percentage of mass retained during the preparation process). The moderately hydrophobic (teicoplanin) and highly hydrophobic (rifampin) antibiotics varied significantly in their encapsulation load (max 23.4 and 15.5%, respectively) and mass yield (max 74.1 and 71.8%, respectively), favoring techniques that maximized partition between the aqueous core and the lipid bilayer or those that produce oligolamellar vesicles, whereas vancomycin hydrochloride, a highly hydrophilic molecule, showed little preference to any of the protocols. In addition, we report significant bias introduced by the choice of analytical method adopted to quantify the encapsulation efficiency (underestimation of up to 24% or overestimation by up to 57.9% for vancomycin and underestimation of up to 61.1% for rifampin) and further propose ultrafiltration and bursting by methanol as the method with minimal bias for quantification of encapsulation efficiency in liposomes. The knowledge generated in this work provides critical insight into the more practical, albeit less investigated, aspects of designing vesicles for localized antibiotic delivery and can be extended to other nanovehicles that may suffer from the same biases in analytical protocols.

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Liposome nanovesicles are attractive vehicles for encapsulation and localized delivery of antibiotics. Most liposomal batch preparation processes involve numerous freeze–thaw cycles and heating or sonication steps, all of which can potentially deactivate or degrade antibiotics. We investigated the extent of antibiotic deactivation during various liposomal preparation methods using two glycopeptide antibiotics clinically administered for Staphylococcus infections, namely, vancomycin hydrochloride and teicoplanin. Both antibiotics, in the nonencapsulated state, were found to be highly sensitive to the freeze–thaw/sonication; vancomycin completely lost efficacy after only three cycles of freeze–thaw, and teicoplanin lost efficacy after 20 min of sonication. When the antibiotics were encapsulated in liposomes, vancomycin retained full potency against bacterial cultures of Staphylococcus aureus but encapsulated teicoplanin suffered a decrease in activity. Differential scanning calorimetry and mass spectrometry suggest that liposomes have a protective effect on the encapsulated antibiotic, the extent of which was found to differ on the basis of the processing conditions.

RESUMENEFECTIVIDAD Y TOLERABILIDAD DEL ÁCIDO ZOLEDRÓNICO EN EL TRATAMIENTO DEL CANCER DE PRÓSTATA METASTÁSICO Objetivos: Evaluar la efectividad y tolerabilidad del ácido zoledrónico en pacientes con cáncer de próstata y metástasis óseas en fase hormonosensible (HS) y hormonoindependiente (HI).Material y Métodos: Se diseñó un estudio de ámbito nacional, observacional, prospectivo, abierto, y multicéntrico, Se incluyeron un total de 218 varones diagnosticados de cáncer de próstata en fase HS (36%) o HI (64%) que recibieron, además del tratamiento oncológico específico, ácido zoledrónico (4 mg/IV/mes durante 6 meses).Se evaluó la efectividad mediante: 1) Evaluación de la mejoría del dolor y movilidad; 2) Incidencia y tiempo de aparición de eventos esqueléticos (TEE); y 3) Análisis de marcadores óseos.La tolerabilidad se estudió registrando el número y tipo de efectos adversos. Se realizó una encuesta de satisfacción al paciente tras finalizar el tratamiento.Resultados: De los 218 pacientes, 170 (78%) fueron evaluables para efectividad. En todos ellos, ya fueran del grupo HS o HI, se observó una disminución de la puntuación del dolor en reposo y en movimiento (p<0,0001), una mejora en la movilidad (p=0,005), y en la calidad de vida.La incidencia global de eventos esqueléticos fue del 11,2%, con un TEE de 10,7 meses. No hubo diferencias significativas entre los pacientes HS respecto a los HI. Los marcadores de osteolisis (N-telopéptido) descendieron significativamente con el tratamiento, tanto en los HS como HI.Para seguridad fueron evaluables 212 pacientes (97,2%). La incidencia de las reacciones adversas fue del 16% (34/212), siendo significativamente mayor en los pacientes HS (22,4%) con respecto a los HI (11,9%). Globalmente la tolerabilidad al ácido zoledrónico fue buena, sin morbilidad significativa entre ambos grupos (HS y HI).Un 66% de los pacientes contestaron sentirse satisfechos o muy satisfechos. Conclusiones: El ácido zoledrónico se mostró eficaz para aliviar el dolor, mejorar la movilidad y aumentar la calidad de vida y reducir o retrasar los eventos esqueléticos en los pacientes con cáncer de próstata con enfermedad ósea metastásica sintomática, independientemente de la fase, HS o HI en que se encuentren. La tolerabilidad y la satisfacción de los pacientes fue buena.Palabras clave: Cáncer de próstata metastásico. Ácido Zoledrónico. Eventos óseos. Calidad de vida. ABSTRACT EFFECTIVENESS AND TOLERABILITY OF ZOLEDRONIC ACID IN THE TREATMENT OF METASTATIC PROSTATE CANCERObjetives: To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages.Materials and Methods: A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment.Effectiveness was assessed ...

Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.