Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics

Abstract

Background and aimDrugs that are effective against diseases in the central nervous system and reach the brain via blood must pass through the blood–brain barrier (BBB), a unique interface that protects against potential harmful molecules. This presents a major challenge in neuro-drug delivery. This study attempts to fabricate the cefuroxime-loaded nanoemulsion (CLN) to increase drug penetration into the brain when parenterally administered.MethodsThe nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties.ResultsThe characterizations revealed a particle size of 100.32±0.75 nm, polydispersity index of 0.18±0.01, zeta potential of −46.9±1.39 mV, viscosity of 1.24±0.34 cps, and osmolality of 285.33±0.58 mOsm/kg, indicating that the nanoemulsion has compatibility for parenteral application. CLN was physicochemically stable within 6 months of storage at 4°C, and the transmission electron microscopy revealed that the CLN droplets were almost spherical in shape. The in vitro release of CLN profile followed a sustained release pattern. The pharmacokinetic profile of CLN showed a significantly higher Cmax, area under the curve (AUC)0–t, prolonged half-life, and lower total plasma clearance, indicating that the systemic concentration of cefuroxime was higher in CLN-treated rats as compared to cefuroxime-free treated rats. A similar profile was obtained for the biodistribution of cefuroxime in the brain, in which CLN showed a significantly higher Cmax, AUC0–t, prolonged half-life, and lower clearance as compared to free cefuroxime solution.ConclusionOverall, CLN showed excellent physicochemical properties, fulfilled the requirements for parenteral administration, and presented improved in vivo pharmacokinetic profile, which reflected its practical approach to enhance cefuroxime delivery to the brain.

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“…The results indicated that the release behavior of NAR depends on the nanoemulsion formulation type and is independent of pH value [ 21 ]. A similar pattern for nanoemulsions has been reported elsewhere [ 21 , 22 , 36 ]. The drug release from the nanoemulsion is connected to the diffusion of droplets into the surrounding layers of surfactants in the buffer medium.…”

Formulation and Characterization of Eplerenone Nanoemulsion Liquisolids, An Oral Delivery System with Higher Release Rate and Improved Bioavailability

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Nanotechnological strategies for systemic microbial infections treatment: A review

“…Infectious diseases affecting the CNS such as meningitis (meningeal and subarachnoid space inflammation, which may involve the cerebral cortex and parenchyma), require delivery of the drug directly to the target organ for therapy ( van de Beek et al, 2016 ). Harun et al (2018) synthesized a CLN containing cefuroxime, a drug that has difficulty permeating the blood–brain barrier (BBB) due to its limited fat solubility. The CLN consisted of an oil phase prepared with cefuroxime (0.3%, w / w) mixture of oil (10%, w / w) and lecithin (3%, w / w) as surfactant.…”