Lipid Core Nanocapsules for Antimicrobials Drug Delivery

Over the past years, the development of biodegradable nanoparticulate systems for drug delivery has aroused great interest. Substantial advances happened in the development of functional nanomaterials towards biomedical materials, mainly for targeted therapies and drug delivery. Lipid core nanocapsules (LCN), a class of nanocapsules in which a polymeric shell is arranged around an inner core and is formed by a dispersion of a liquid lipid and a solid lipid, have gained attention since they can vehicle actives soluble in their lipidic core or polymeric shell. PCL (poly-E-caprolactone), a biocompatible and biodegradable polymer, has been used to encapsulate a wide range of drugs, achieving targeted and controlled drug delivery. Fluconazole, a bis-triazole antifungal, and rifamycin SV, an ansamycin antibiotic, could benefit from encapsulation. Our objective was to encapsulate fluconazole and rifamycin SV in LCN, aiming to improve existing treatments by controlling their release. Empty-LCN (unloaded), Flu-LCN (LCN loaded with fluconazole) and Rif-LCN (LCN loaded with rifamycin SV) were prepared as previously described. Empty-LCN presented mean diameter of 220 nm, with PDI around 0.13 and zeta potential of -27 mV, while Flu-LCN and Rif-LCN presented around 230 nm diameter, PDI 0.15 and -28 mV zeta potential, determined by DLS in ZetaSizer Nano ZS equipment. Total drug concentration was determined by HPLC/UV, as well as encapsulation efficiency after separating non-encapsulated drug by ultrafiltration-centrifugation. Fluconazole presented a type II distribution in LCN, with encapsulation efficiency calculated as 8.0%, drug content of 798 µg/mL and drug loading of 0.17%. On the other hand, rifamycin SV presented a type III distribution, with encapsulation efficiency of 66.2%, drug content of 743 µg/mL and drug loading of 1.28%. Profile of drug release from LCN was determined by in vitro Franz-cell diffusion. Around 53% of fluconazole was released in the first 7h, reaching 77% in 48h; while less than 5% of rifamycin SV was released in the first 8h, reaching 21% in 48h. <i>In vitro </i>antimicrobial activity of free drugs and LCN formulations was determinate using minimal inhibitory concentration (MIC) method against <i>S. aureus</i>, <i>P. aeruginosa </i>and <i>C. albicans </i>microorganisms. Empty-LCN did not show any antimicrobial activity. Free-Flu and Flu-LCN did not showed activity in the tested concentrations for <i>S. aureus </i>and <i>P. aeruginosa</i>, and a MIC of 0.39 µg/mL for <i>C. albicans</i>. Free-Rif and Rif-LCN showed MIC of 3.1x10^-3 µg/mL for <i>S. aureus</i>, 100 ug/mL for <i>P. aeruginosa</i>, and no activity against <i>C. albicans</i>. LCN formulations with fluconazole and rifamycin SV were successfully produced. Depending on drug characteristics, higher encapsulation efficiency and drug loading was achieved, with a more prolonged release. Antimicrobial activity of fluconazole and rifamycin SV was maintained after encapsulation in LCN formulations, and no activity was reported for empty-LCN.