Oral delivery of lycopene-loaded microemulsion for brain-targeting: preparation, characterization, pharmacokinetic evaluation and tissue distribution

Drug Delivery

Xuyan Mao¹  Jing Zhang²  Song Xu³  Yunliang Guo³  Yingjuan Ma³  Yue Zhang³  Xueping Liu⁴  Peng Sun⁵  Haiyang Wang⁵  Renjun Lv⁶ 

[1]Bio-nano & Medical Engineering Institute, Jining Medical University, Jining, PR China

[2]Department of Cell and Neurobiology, School of Basic Medical Sciences, Shandong University, Jinan, PR China

[3]Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[4]Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[5]Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[6]Department of Geriatrics, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[7]Department of Geriatric Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[8]Anti-Aging Monitoring Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR China

[9]Department of Anti-Aging, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, PR Chin

[10]Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, PR China

[11]Shandong Provincial Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, PR China

关键词: Lycopene;    microemulsion;    pharmacokinetic study;    tissue distribution;    brain-targeting;   

DOI  :  10.1080/10717544.2019.1689312

来源: publisher

【 摘 要 】

Lycopene is considered as a promising neuroprotector with multiple bioactivities, while its therapeutic use in neurological disorders is restricted due to low solubility, instability and limited bioavailability. Our work aimed to develop lycopene-loaded microemulsion (LME) and investigate its potentials in improving bioavailability and brain-targeting efficiency following oral administration. The blank microemulsion (ME) excipients were selected based on orthogonal design and pseudo-ternary phase diagrams, and LME was prepared using the water titration method and characterized in terms of stability, droplet size distribution, zeta potential, shape and lycopene content. The optimized LME encompassed lycopene, (R)-(+)-limonene, Tween 80, Transcutol HP and water and lycopene content was 463.03 ± 8.96 µg/mL. This novel formulation displayed transparent appearance and satisfactory physical and chemical stabilities. It was spherical and uniform in morphology with an average droplet size of 12.61 ± 0.46 nm and a polydispersity index (PDI) of 0.086 ± 0.028. The pharmacokinetics and tissue distributions of optimized LME were evaluated in rats and mice, respectively. The pharmacokinetic study revealed a dramatic 2.10-fold enhancement of relative bioavailability with LME against the control lycopene dissolved in olive oil (LOO) dosage form in rats. Moreover, LME showed a preferential targeting distribution of lycopene toward brain in mice, with the value of drug targeting index (DTI) up to 3.45. In conclusion, the optimized LME system demonstrated excellent physicochemical properties, enhanced oral bioavailability and superior brain-targeting capability. These findings provide a basis for the applications of ME-based strategy in brain-targeted delivery via oral route, especially for poorly water-soluble drugs.

【 授权许可】

CC BY