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

• Main Authors: Harun, Siti Norhawani, Amin Nordin, Syafinaz, Abd Gani, Siti Salwa, Shamsuddin, Ahmad Fuad, Basri, Mahiran, Basri, Hamidon
• Format: Article
• Language: English
• Published: Dove Medical Press 2018
• Online Access: http://psasir.upm.edu.my/id/eprint/72266/1/development-of-nanosystem-efficient-utilizing-emulsion-for-b_042618.pdf; http://psasir.upm.edu.my/id/eprint/72266/; https://www.dovepress.com/development-of-nanoemulsion-for-efficient-brain-parenteral-delivery-of-peer-reviewed-article-IJN

Background and aim: Drugs 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. Methods: The nanoemulsions were formulated using a high-pressure homogenization technique and were characterized for their physicochemical properties. Results: The 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. Conclusion: Overall, 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.