Advertisement

AAPS PharmSciTech

, 21:62 | Cite as

Preparation and Characterization of Honokiol Nanosuspensions and Preliminary Evaluation of Anti-Inflammatory Effect

  • Xinyue Lu
  • Xiaoyu Lu
  • Zhenhai ZhangEmail author
  • Huixia LvEmail author
Research Article
  • 23 Downloads

Abstract

The study mainly aimed to improve the solubility of honokiol (HK) by preparing honokiol nanosuspensions (HNS). In this study, HNS were obtained using Kolliphor®P407 (P407) as a stabilizer through melting method combined with high pressure homogenization (HPH). The crystalline state of HNS was confirmed through differential scanning calorimetry (DSC) and X-ray Diffraction (XRD). In vitro, the dissolution rate of HNS was significantly improved than that of pure HK. In vivo, higher anti-inflammatory activity was achieved after free HK had been made into HNS. There was no significant difference between the degree of edema (DE) of HNS group and that of aspirin group. Consequently, melting method combined with HPH was a potent technique to prepare HNS. Furthermore, nanosuspension was a valid formulation that could be utilized to enhance the anti-inflammatory effect of HK.

KEY WORDS

honokiol nanosuspensions melting method high pressure homogenization anti-inflammatory activity 

Notes

Funding Information

This work was financially supported by the National Natural Science Foundation of China (81673830), six talent peaks project of Jiangsu Province (YY053), Major Project and Double first -class innovative team (CPU2018GY28), and National Science and Technology Major Project (2017zx09101001005).

References

  1. 1.
    Fujita M, Itokawa H, Sashida Y. Honokiol, a new phenolic compound isolated from the bark of Magnolia obovata Thunb. Chem Pharm Bull. 1972;20:212–3.CrossRefGoogle Scholar
  2. 2.
    Huang DB, Yu ZF. Effects of honokiol and magnolol on beta-endorphin in relieving morphine withdrawal symptoms in rats. Chin J Clin Rehabil. 2005;2(9):831–2.Google Scholar
  3. 3.
    Liou KT, Shen YC, Chen CF, Tsao CM, Tsai SK. The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production. Eur J Pharmacol. 2003;475(1):19–27.PubMedCrossRefGoogle Scholar
  4. 4.
    Kuribara H, Stavinoha WB, Maruyama Y. Behavioural pharmacological characteristics of honokiol, an anxiolytic agent present in extracts of Magnolia bark, evaluated by an elevated plus-maze test in mice. J Pharm Pharmacol. 2011;50(7):819–26.CrossRefGoogle Scholar
  5. 5.
    Shen J-L, Man K-M, Huang P-H, Chen W-C, Chen D-C, Cheng Y-W, et al. Honokiol and magnolol as multifunctional antioxidative molecules for dermatologic disorders. Molecules. 2010;15(9):6452–65.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Rauf A, Patel S, Imran M, Maalik A, Arshad MU, Saeed F, et al. Honokiol: an anticancer lignan. Biomed Pharmacother. 2018;107:555–62.PubMedCrossRefGoogle Scholar
  7. 7.
    Jongsung L, Eunsun J, Junho P, Kwangseon J, Sangyeop L, Sungtaek H, et al. Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling. Planta Med. 2005;71(04):338–43.CrossRefGoogle Scholar
  8. 8.
    Guo Y, Zhao Y, Wang T, Shuang Z, Qiu H, Han M, et al. Honokiol nanoparticles stabilized by oligoethylene glycols codendrimer: in vitro and in vivo investigation. J Mater Chem B. 2016;5(4):697–706.CrossRefGoogle Scholar
  9. 9.
    Wang N, Wang Z, Nie S, Song L, He T, Yang S, et al. Biodegradable polymeric micelles coencapsulating paclitaxel and honokiol: a strategy for breast cancer therapy in vitro and in vivo. Int J Nanomedicine. 2017;12:1499–514.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Han M, Yu X, Guo Y, Wang Y, Kuang H, Wang X. Honokiol nanosuspensions: preparation, increased oral bioavailability and dramatically enhanced biodistribution in the cardio-cerebrovascular system. Colloids Surf B: Biointerfaces. 2014;116(2):114–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Jiang Q, Fan L, Yang G, Guo WH, Hou W, Chen L, et al. Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model. BMC Cancer. 2008;8(1):242.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Gao L, Zhang D, Chen M. Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system. J Nanopart Res. 2008;10(5):845–62.CrossRefGoogle Scholar
  13. 13.
    Müller RH, Gohla S, Keckacd CM. State of the art of nanocrystals – special features, production, nanotoxicology aspects and intracellular delivery. Eur J Pharm Biopharm. 2011;78(1):1–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Junghanns JUAH, Müller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295–310.PubMedPubMedCentralGoogle Scholar
  15. 15.
    Lai F, Pini E, Corrias F, Perricci J, Manconi M, Fadda AM, et al. Formulation strategy and evaluation of nanocrystal piroxicam orally disintegrating tablets manufacturing by freeze -drying. Int J Pharm. 2014;467(1–2):27–33.PubMedCrossRefGoogle Scholar
  16. 16.
    Lin Z, Gao W, Hu H, Ma K, He B, Dai W, et al. Novel thermo-sensitive hydrogel system with paclitaxel nanocrystals: high drug-loading, sustained drug release and extended local retention guaranteeing better efficacy and lower toxicity. J Control Release. 2014;174(1):161–70.PubMedCrossRefGoogle Scholar
  17. 17.
    Möschwitzer J, Müller RH. Spray coated pellets as carrier system for mucoadhesive drug nanocrystals. Eur J Pharm Biopharm. 2006;62(3):282–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Chan HK, Kwok PCL. Production methods for nanodrug particles using the bottom-up approach. Adv Drug Deliv Rev. 2011;63(6):406–16.PubMedCrossRefGoogle Scholar
  19. 19.
    Biswadip S, Müller RH, MöSchwitzer JP. Bottom-up approaches for preparing drug nanocrystals: formulations and factors affecting particle size. Int J Pharm. 2013;453(1):126–41.CrossRefGoogle Scholar
  20. 20.
    Elaine M-L, Gary GL, Eugene RC. Nanosizing: a formulation approach for poorly-water-soluble compounds. Eur J Pharm Sci. 2003;18(2):113–20.CrossRefGoogle Scholar
  21. 21.
    Chin WWL, Johannes P, Michael W, En Hui T, Rajeev G. A brief literature and patent review of nanosuspensions to a final drug product. J Pharm Sci. 2015;103(10):2980–99.CrossRefGoogle Scholar
  22. 22.
    Federica L, Roberta C. Drug nanosuspensions: a ZIP tool between traditional and innovative pharmaceutical formulations. Expert Opin Drug Deliv. 2015;12(10):1607–25.CrossRefGoogle Scholar
  23. 23.
    Ji Y, Zhou X, Guo R, Nie F, Wang X. Honokiol nanosuspensions: preparation, in vitro and in vivo evaluation. Acta Pharm Sin. 2018;29(1):133–40.Google Scholar
  24. 24.
    Zheng H, Yu X, Li Z. Preparation of honokiol nanoparticles with high drug-loading and their premilinary antitumor efficacy. Drug Eval Res. 2015;38(3):292–6.Google Scholar
  25. 25.
    Wu W, Wang L, Wang L, Zu Y, Wang S, Liu P, et al. Preparation of honokiol nanoparticles by liquid antisolvent precipitation technique, characterization, pharmacokinetics, and evaluation of inhibitory effect on HepG2 cells. Int J Nanomedicine. 2018;13:5469–83.PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Wang Z, Li X, Wang D, Zou Y, Qu X, He C, et al. Concurrently suppressing multidrug resistance and metastasis of breast cancer by co-delivery of paclitaxel and honokiol with pH-sensitive polymeric micelles. Acta Biomater. 2017;62(15):144–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Deng F, Hu W, Chen H, Tang Y, Zhang L. Development of a chitosan-based nanoparticle formulation for ophthalmic delivery of honokiol. Current Drug Delivery. 2018;15(4):594–600.PubMedCrossRefGoogle Scholar
  28. 28.
    Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Deliv Rev. 2001;47(1):3–19.PubMedCrossRefGoogle Scholar
  29. 29.
    Teeranachaideekul V, Junyaprasert VB, Souto EB, Müller RH. Development of ascorbyl palmitate nanocrystals applying the nanosuspension technology. Int J Pharm. 2008;354(1):227–34.PubMedCrossRefGoogle Scholar
  30. 30.
    Wenju WU. NANCOLLAS, G. H. a new understanding of the relationship between solubility and particle size. J Solut Chem. 1998;27(6):521–31.CrossRefGoogle Scholar
  31. 31.
    Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions. J Am Chem Soc. 1897;19(12):930–4.CrossRefGoogle Scholar
  32. 32.
    Kumawat R, Sharma S, Vasudeva N, Kumar S. In vivo anti-inflammatory potential of various extracts of Sida tiagii Bhandari. Asian Pac J Trop Biomed. 2012;2(2):S947–S52.CrossRefGoogle Scholar
  33. 33.
    Sowemimo A, Samuel F, Fageyinbo MS. Anti-inflammatory activity of Markhamia tomentosa (Benth.) K. Schum. Ex Engl. ethanolic leaf extract. J Ethnopharmacol. 2013;149(1):191–4.PubMedCrossRefGoogle Scholar
  34. 34.
    Levy G, Giacomini KM. Rational aspirin dosage regimens. Clin Pharmacol Ther. 1978;23(3):247–52.CrossRefGoogle Scholar
  35. 35.
    Bernstein BH, Singsen BH, King KK, Hanson V. Aspirin-induced hepatotoxicity and its effect on juvenile rheumatoid arthritis. Am J Dis Child. 1960;131(6):659–63.CrossRefGoogle Scholar
  36. 36.
    Byung Hun K, Jae YC. Anti-inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression 1. Acta Pharmacol Sin. 2010;29(1):113–22.Google Scholar
  37. 37.
    Li J, Shao X, Wu L, Feng T, Jin C, Fang M, et al. Honokiol: an effective inhibitor of tumor necrosis factor-α-induced up-regulation of inflammatory cytokine and chemokine production in human synovial fibroblasts. Acta Biochim Biophys Sin. 2011;43(5):380–6.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  1. 1.Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Nanjing University of Chinese MedicineNanjingChina
  2. 2.Jiangsu Province Academy of Traditional Chinese MedicineNanjingChina
  3. 3.Department of Pharmaceutics, State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjingChina

Personalised recommendations