WANG Zhongjuan, LI Zihan, ZHANG Xiujuan, et al. Formulation, Characterization and Pharmacokinetic Studies of Pinus koraiensis Nuts Oil Based Coenzyme Q10 Loaded Nanoemulsion[J]. Science and Technology of Food Industry, 2022, 43(21): 225−234. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022020080.
Citation: WANG Zhongjuan, LI Zihan, ZHANG Xiujuan, et al. Formulation, Characterization and Pharmacokinetic Studies of Pinus koraiensis Nuts Oil Based Coenzyme Q10 Loaded Nanoemulsion[J]. Science and Technology of Food Industry, 2022, 43(21): 225−234. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022020080.

Formulation, Characterization and Pharmacokinetic Studies of Pinus koraiensis Nuts Oil Based Coenzyme Q10 Loaded Nanoemulsion

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  • Received Date: February 13, 2022
  • Available Online: August 28, 2022
  • Coenzyme Q10 nanoemulsion (CoQ10-NE) was improved and made utilizing Pinus koraiensis nuts oil as the oil phase, soybean lecithin as the surfactant, and ethanol as the cosurfactant in this study. The effects of different factors on the mean particle size and polydispersity index (PDI) of CoQ10-NE were studied, and the quality was evaluated by DLS, TEM, FT-IR, stability, in vitro release behavior and in vivo pharmacokinetic experiments in rats.The results showed that when the mass ratio of CoQ10 to mixed surfactant was 3:40, the mass ratio of CoQ10 to Pinus koraiensis nuts oil was 1:4, the homogenizing pressure was 800 bar, and the number of cycles was 6 times, the CoQ10-NE of mean particle size of 150.30±1.43 nm and PDI of 0.234±0.012 was obtained. The morphology and microstructure showed that the CoQ10-NE was round and non-adhesive at the size of 500 nm and 1 µm. FT-IR results showed that CoQ10 was completely encapsulated in nanoemulsion. The stability experiment showed that there was no significant difference in the mean particle size and PDI (P>0.05). CoQ10-NE had good stability. In vitro release experiments showed that the cumulative dissolution rate of CoQ10-NE was 4.7-fold that of the CoQ10 suspension at 120 min. The dissolution rate was significantly improved. According to the results of pharmacokinetic investigations in rats, the maximum plasma concentration Cmax of CoQ10-NE was 2.80-fold that of CoQ10 suspension, the drug concentration of CoQ10-NE in rats was greatly enhanced. The area AUC0- was 3.25-fold that of the CoQ10 suspension, demonstrating that CoQ10-NE bioavailability and absorption were greatly increased. The CoQ10-NE developed in this study provides a theoretical foundation for investigating the creation of new CoQ10 formulations and their potential application as a functional ingredient in food.
  • [1]
    RAIZNER A E. Coenzyme Q10[J]. Methodist DeBakey Cardiovascular Journal,2019,15(3):185−191. doi: 10.14797/mdcj-15-3-185
    [2]
    YANG C X, LIU S, MIAO J K, et al. CoQ10 improves meiotic maturation of pig oocytes through enhancing mitochondrial function and suppressing oxidative stress[J]. Theriogenology,2021,159:77−86. doi: 10.1016/j.theriogenology.2020.10.009
    [3]
    ELSHAZLY S M, ALSEMEH A E, AHMAD E A A, et al. CoQ10 exerts hepatoprotective effect in fructose-induced fatty liver model in rats[J]. Pharmacological Reports,2020,72(4):922−934. doi: 10.1007/s43440-020-00075-5
    [4]
    AGAMY D, NAGUIB Y M. CoQ10 ameliorates monosodium glutamate-induced alteration in detrusor activity and responsiveness in rats via anti-inflammatory, anti-oxidant and channel inhibiting mechanisms[J]. BMC Urology,2019,19(1):103. doi: 10.1186/s12894-019-0534-9
    [5]
    ZOZINA V, COVANTEV S, GOROSHKO O, et al. Coenzyme Q10 in cardiovascular and metabolic diseases: Current state of the problem[J]. Current Cardiology Reviews,2018,14(3):164−174. doi: 10.2174/1573403X14666180416115428
    [6]
    AASETH J, ALEXANDER J, ALEHAGEN U. Coenzyme Q10 supplementation-in ageing and disease[J]. Mechanisms of Ageing and Development,2021,197:111521. doi: 10.1016/j.mad.2021.111521
    [7]
    TAFAZOLI A. Coenzyme Q10 in breast cancer care[J]. Future Oncology,2017,13(11):1035−1041. doi: 10.2217/fon-2016-0547
    [8]
    AF MARÍA, EVA T, GLORIA B C. Clinical syndromes associated with coenzyme Q10 deficiency[J]. Essays in Biochemistry,2018,62(3):377−398. doi: 10.1042/EBC20170107
    [9]
    PRAVST I, AGUILERA J, RODRIGUEZ A, et al. Comparative bioavailability of different coenzyme Q10 formulations in healthy elderly individuals[J]. Nutrients,2020,12(3):784. doi: 10.3390/nu12030784
    [10]
    CHEN X, ZHANG Y, WANG Z, et al. In vivo antioxidant activity of Pinus koraiensis nut oil obtained by optimised supercritical carbon dioxide extraction[J]. Natural Product Research,2011,25(19):1807−1816. doi: 10.1080/14786419.2010.483229
    [11]
    SHPATOV A V, POPOV S A, SALNIKOVA O I, et al. Composition and bioactivity of lipophilic metabolites from needles and twigs of Korean and Siberian Pines (Pinus koraiensis Siebold & Zucc. and Pinus sibirica Du Tour)[J]. Chemistry & Biodiversity, 2017, 14(2):e1600203.
    [12]
    TAKALA R, RAMJI D P, ANDREWS R, et al. Anti-inflammatory and immunoregulatory effects of pinolenic acid in rheumatoid arthritis[J]. Rheumatology (Oxford),2022,61(3):992−1004. doi: 10.1093/rheumatology/keab467
    [13]
    ZHANG Y, XIN C, QIU J, et al. Essential oil from Pinus koraiensis pinecones inhibits gastric cancer cells via the HIPPO/YAP signaling pathway[J]. Molecules,2019,24(21):3851. doi: 10.3390/molecules24213851
    [14]
    SINGH Y, MEHER J G, RAVAL K, et al. Nanoemulsion: Concepts, development and applications in drug delivery[J]. Journal of Controlled Release,2017,252:28−49. doi: 10.1016/j.jconrel.2017.03.008
    [15]
    PANDEY P, GULATI N, MAKHIJA M, et al. Nanoemulsion: A novel drug delivery approach for enhancement of bioavailability[J]. Recent Patents on Nanotechnology,2020,14(4):276−293. doi: 10.2174/1872210514666200604145755
    [16]
    张平. 复合抗衰老纳米乳液的制备及其应用评估[D]. 南京: 东南大学, 2017

    ZHANG Ping. Preparation and application evaluation of compound antiaging nano emulsion[D]. Nanjing: Southeast University, 2017.
    [17]
    FAN H, LIU G, HUANG Y, et al. Development of a nanostructured lipid carrier formulation for increasing photo-stability and water solubility of phenylethyl resorcinol[J]. Applied Surface Science,2014,288:193−200. doi: 10.1016/j.apsusc.2013.10.006
    [18]
    BHALEKAR M R, POKHARKAR V, MADGULKAR A, et al. Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery[J]. AAPS Pharm Sci Tech,2009,10(1):289−296. doi: 10.1208/s12249-009-9199-0
    [19]
    ZHONG Y, WANG J, WANG Y, et al. Preparation and evaluation of liposome-encapsulated codrug LMX[J]. International Journal of Pharmaceutics,2012,438(1-2):240−248. doi: 10.1016/j.ijpharm.2012.08.051
    [20]
    周佳, 孙燕燕, 温美强, 等. 布洛芬口服纳米乳的制备及处方优化研究[J]. 沈阳药科大学学报,2020,37(10):865−871. [ZHOU Jia, SUN Yanyan, WEN Meiqiang, et al. Preparation and optimization of ibuprofen loaded oral nanoemulsion[J]. Journal of Shenyang Pharmaceutical University,2020,37(10):865−871. doi: 10.14066/j.cnki.cn21-1349/r.2020.10.001
    [21]
    KHATTAB A, HASSANIN L, ZAKI N. Self-nanoemulsifying drug delivery system of coenzyme Q10 with improved dissolution, bioavailability, and protective efficiency on liver fibrosis[J]. AAPS Pharm Sci Tech,2017,18(5):1657−1672. doi: 10.1208/s12249-016-0632-x
    [22]
    KACI M, ARAB-TEHRANY E, DOSTERT G, et al. Efficiency of emulsifier-free emulsions and emulsions containing rapeseed lecithin as delivery systems for vectorization and release of coenzyme Q10: Physico-chemical properties and in vitro evaluation[J]. Colloids and Surfaces B: Biointerfaces,2016,147:142−150. doi: 10.1016/j.colsurfb.2016.07.036
    [23]
    KOMMURU T R, GURLEY B; KHAN M A, et al. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: Formulation development and bioavailability assessment[J]. International Journal of Pharmaceutics,2001,212(2):233−246. doi: 10.1016/S0378-5173(00)00614-1
    [24]
    HALLOUARD F, DOLLO G, BRANDHONNEUR N, et al. Preparation and characterization of spironolactone-loaded nanoemulsions for extemporaneous applications[J]. International Journal of Pharmaceutics,2015,478(1):193−201. doi: 10.1016/j.ijpharm.2014.11.046
    [25]
    杨璇. 辅酶Q10纳米制剂制备、表征及其生物效应研究[D]. 哈尔滨: 东北林业大学, 2018

    YANG Xuan. Preparation, characterization and biological effects of coenzyme Q10 nanoemulsion[D]. Harbin: Northeast Forestry University, 2018.
    [26]
    GARAVAND F, JALAI-JIVAN M, ASSADPOUR E, et al. Encapsulation of phenolic compounds within nano/microemulsion systems: A review[J]. Food Chemistry,2021,364(4):130376.
    [27]
    WU Y, PETROCHENKO P, MYUNG J H, et al. Distinguish coexistence of nanoemulsion and liposome in propofol by cryogenic transmission electron microscopy (cryo-TEM)[J]. Microscopy & Microanalysis,2017,23(S1):852−853.
    [28]
    YULIATI L. Curcumin-loaded nanoemulsion for better cellular permeation[J]. Scientia Pharmaceutica,2020,88(4):44. doi: 10.3390/scipharm88040044
    [29]
    TUBESHA Z, ABUBAKAR Z, ISMAIL M. Characterization and stability evaluation of thymoquinone nanoemulsions prepared by high-pressure homogenization[J]. Journal of Nanomaterials,2013,2013:1−6.
    [30]
    SABJAN K B, MUNAWAR S M, RAJENDIRAN D, et al. Nanoemulsion as oral drug delivery-A review[J]. Current Drug Research Reviews,2020,12(1):4−15. doi: 10.2174/2589977511666191024173508
    [31]
    CHUTIA H, MAHANTA C L. Properties of starch nanoparticle obtained by ultrasonication and high pressure homogenization for developing carotenoids-enriched powder and pickering nano-emulsion[J]. Innovative Food Science and Emerging Technologies,2021,74:102822. doi: 10.1016/j.ifset.2021.102822
    [32]
    KHAN A W, KOTTA S, ANSARI S H, et al. Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: Design, characterization, in vitro and in vivo evaluation[J]. Drug Delivery,2015,22(4):552−561. doi: 10.3109/10717544.2013.878003
    [33]
    陈家铃, 吴航航, 何益飞, 等. 水杨酸纳米乳的制备、体外释放行为及抑菌活性研究[J]. 精细与专用化学品,2022,30(3):16−21. [CHEN Jialing, WU Hanghang, HE Yifei, et al. Preparation, in vitro release behavior and antibacterial activity of salicylic acid nanoemulsion[J]. Fine and Specialty Chemicals,2022,30(3):16−21. doi: 10.19482/j.cn11-3237.2022.03.04
    [34]
    CHHABRA G, CHUTTANI K, MISHRA A K, et al. Design and development of nanoemulsion drug delivery system of amlodipine besilate for improvement of oral bioavailability[J]. Drug Development and Industrial Pharmacy,2011,37:907−916. doi: 10.3109/03639045.2010.550050
    [35]
    BELHAJ N, DUPUIS F, ARAB-TEHRANY E, et al. Formulation, characterization and pharmacokinetic studies of coenzyme Q10 PUFA's nanoemulsions[J]. European Journal of Pharmaceutical Sciences,2012,47(2):305−312. doi: 10.1016/j.ejps.2012.06.008

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