Skip to main content

Advertisement

SpringerLink
Log in

Preparation of a Unique Bioavailable Bacoside Formulation (Cognique®) Using Polar-Nonpolar-Sandwich (PNS) Technology and Its Characterization, In Vitro Release Study, and Proposed Mechanism of Action

  • Original Research
  • Published:
Regenerative Engineering and Translational Medicine Aims and scope Submit manuscript

Abstract

Bacopa monnieri Linn. (B. monnieri) is a medicinal herb that has been utilized as a traditional medicine to improve memory and learning. Bacosides, the important components of B. monnieri, are used in Ayurvedic herbal formulation to improve cognitive and neuroprotective action and as therapeutics for the management of many central nervous disorders. A novel bioavailable bacoside formulation, Cognique®, was prepared through the preservation of bacosides with complete multiple natural matrix including gingerols and rosemary extracts containing rosemary essential oil, rosmarinic acid, and carnosic acid using Polar-Nonpolar-Sandwich (PNS) technology. The successful PNS formulation of Cognique® was confirmed by different instrumental methods. The SEM images clearly indicated that Cognique® was almost well dispersed and has hollow core nest-like spherical structure with porous nature and rough surface due to the interaction between the polar-bacosides-nonpolar matrixes. IR, XRD, and DSC studies also confirmed the existence of bacosides in Cognique® with high stability due to the PNS formulation. The stability and in vitro drug release studies revealed that the PNS technology is an advanced technology to preserve the bioactive components, particularly bacosides, and they are capable of maintaining the sustained release of bacosides at target sites. The existence of synergistic effects of bacosides, extracts of rosemary, and gingerols in Cognique® can be utilized as a natural nutritional supplement for supporting neuroprotective effect and cognition improvement through maintenance of gut-brain axis.

Lay Summary

This study demonstrated a novel bioavailable bacoside formulation—Cognique®—through the preservation of bacosides with multiple natural matrix. Future study will investigate the efficacy, safety, and improvement of normal cognitive function in human volunteers.

Preparation of a unique bioavailable bacoside formulation (Cognique®) using Polar-Nonpolar-Sandwich (PNS) technology and its characterization, in vitro study, and proposed mechanism of action

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Jose S, Sowmya S, Cinu TA, Aleykutty NA, Thomas S, Souto EB. Surface modified PLGA nanoparticles for brain targeting of bacoside-A. Eur J Pharm Sci. 2014;63:29–35.

    Article  CAS  Google Scholar 

  2. Williams R, Munch G, Gyengesi E, Bennett L. Bacopa monnieri (L.) exerts anti-inflammatory effects on cells of the innate immune system in vitro. Food Funct. 2014;5:517–20.

    Article  CAS  Google Scholar 

  3. Nemetchek MD, Stierle AA, Stierle DB, Lurie DI. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. J Ethnopharmacol. 2017;197:92–100.

    Article  Google Scholar 

  4. Sukumaran NP, Amalraj A, Gopi S. Neuropharmacological and cognitive effects of Bacopa monnieri (L.) Wettst—a review on its mechanistic aspects. Complement Ther Med. 2019;44:68–82.

    Article  Google Scholar 

  5. Deepak M, Sangli GK, Arun PC, Amit A. Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC. Phytochem Anal. 2005;16:24–9.

    Article  CAS  Google Scholar 

  6. Christopher C, Johnson AJ, Mathew PJ, Baby S. Elite genotypes of Bacopa monnieri with high contents of bacoside A and bacopaside I, from southern Western Ghats in India. Ind Crop Prod. 2017;98:76–81.

    Article  CAS  Google Scholar 

  7. Srivastava P, Raut HN, Puntambekar HM, Desai AC. Stability studies of crude plant material of Bacopa monnieri and quantitative determination of bacopaside I and bacoside A by HPLC. Phytochem Anal. 2012;23:502–7.

    Article  CAS  Google Scholar 

  8. Amalraj A, Jude S, Varma K, Jacob J, Gopi S, Oluwafemi OS, et al. Preparation of a novel bioavailable curcuminoid formulation (Cureit™) using Polar-Nonpolar-Sandwich (PNS) technology and its characterization and applications. Mater Sci Eng C Mater Biol Appl. 2017;75:359–67.

    Article  CAS  Google Scholar 

  9. Rahbardar MG, Amin B, Mehri S, Mirnajafi-Zadeh SJ, Hosseinzadeh H. Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: an evidence of anti-oxidative and anti-inflammatory effects. Phytomedicine. 2018;40:59–67.

    Article  CAS  Google Scholar 

  10. Ozarowski M, Mikolajczak PL, Bogacz A, Gryszczynska A, Kujawska M, Jodynis-Liebert J, et al. Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain. Fitoterapia. 2013;91:261–71.

    Article  CAS  Google Scholar 

  11. Semwal RB, Combrinck DKS, Viljoen AM. Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry. 2015;117:554–68.

    Article  CAS  Google Scholar 

  12. Hsiang CY, Cheng HM, Lo HY, Li CC, Chou PC, Lee YC, et al. Ginger and zingerone ameliorate lipopolysaccharide-induced acute systemic inflammation in mice, assessed by nuclear factor-κB bioluminescent imaging. J Agric Food Chem. 2015;63:6051–8.

    Article  CAS  Google Scholar 

  13. Si W, Chen YP, Zhang J, Chen ZY, Chung HY. Antioxidant activities of ginger extract and its constituents toward lipids. Food Chem. 2017;239:1117–25.

    Article  CAS  Google Scholar 

  14. Jafarzadeh A, Nemati M. Therapeutic potentials of ginger for treatment of multiple sclerosis: a review with emphasis on its immunomodulatory, anti-inflammatory and antioxidative properties. J Neuroimmunol. 2018;324:54–75.

    Article  CAS  Google Scholar 

  15. van Tilburg MA, Palsson OS, Ringel Y, Whitehead WE. Is ginger effective for the treatment of irritable bowel syndrome? A double blind randomized controlled pilot trial. Complement Ther Med. 2014;22:17–20.

    Article  Google Scholar 

  16. Gopi S, Amalraj A, Jacob J, Kalarikkal N, Thomas S, Guo Q. Preparation, characterization and in vitro study of liposomal curcumin powder by cost effective nanofiber weaving technology. New J Chem. 2018;42:5117–27.

    Article  CAS  Google Scholar 

  17. AOAC. International official methods of analysis of AOAC. Gaithersberg: AOAC International; 1990.

    Google Scholar 

  18. Goula AM, Adamopoulos KG. Effect of maltodextrin addition during spray drying of tomato pulp in dehumidified air: II. Powder properties. Dry Technol. 2008;26:726–37.

    Article  CAS  Google Scholar 

  19. Ghosh T, Maity TK, Singh J. Evaluation of antitumor activity of stigmasterol, a constituent isolated from Bacopa monnieri Linn aerial parts against Ehrlich ascites carcinoma in mice. Orient Pharm Exp Med. 2011;11:41–9.

    Article  Google Scholar 

  20. Khdary NH, Seddiq WK, Alkurdi ME, Alyamani EJ, Alangari AA. Enhance the antimicrobial activity of silver nanoparticles by manipulating a redox process and controlling the size of the particles. Biomed J Sci Tech Res. 2019;16:12196–204.

    Google Scholar 

  21. Saoji SD, Dave VS, Dhore PW, Bobde YS, Mack C, Gupta D, et al. The role of phospholipid as a solubility- and permeability-enhancing excipient for the improved delivery of the bioactive phytoconstituents of Bacopa monnieri. Eur J Pharm Sci. 2017;108:23–35.

    Article  CAS  Google Scholar 

  22. Amalraj A, Varma K, Jacob J, Divya C, Kunnumakkara AB, Stohs SJ, et al. A novel highly bioavailable curcumin formulation improves symptoms and diagnostic indicators in rheumatoid arthritis patients: a randomized, double-blind, placebo-controlled, two-dose, three-arm, and parallel-group study. J Med Food. 2017;20:1022–30.

    Article  CAS  Google Scholar 

  23. Gopi S, Jacob J, Varma K, Jude S, Amalraj A, Arundhathy CA, et al. Comparative oral absorption of curcumin in a natural turmeric matrix with two other curcumin formulations: an open-label parallel-arm study. Phytother Res. 2017;31:1883–91.

    Article  CAS  Google Scholar 

  24. Jude S, Amalraj A, Kunnumakkara AB, Divya C, Löffler BM, Gopi S. Development of validated methods and quantification of curcuminoids and curcumin metabolites and their pharmacokinetic study of oral administration of complete natural turmeric formulation (Cureit™) in human plasma via UPLC/ESI-Q-TOF-MS spectrometry. Molecules. 2018;23:2415.

    Article  Google Scholar 

  25. Amalraj A, Divya C, Gopi S. The effects of bioavailable curcumin (Cureit) on delayed onset muscle soreness induced by eccentric continuous exercise: a randomized, placebo-controlled, double-blind clinical study. 2020; https://doi.org/10.1089/jmf.2019.4533.

  26. Mishra A, Mishra AK, Jha S. Effect of traditional medicine brahmi vati and bacoside A-rich fraction of Bacopa monnieri on acute pentylenetetrzole-induced seizures, amphetamine-induced model of schizophrenia, and scopolamine-induced memory loss in laboratory animals. Epilepsy Behav. 2018;80:144–51.

    Article  Google Scholar 

  27. Uabundit N, Wattanathorn J, Mucimapura S, Ingkaninan K. Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer’s disease model. J Ethnopharmacol. 2010;127:26–31.

    Article  Google Scholar 

  28. Krebs-Kraft DL, et al. The memory-impairing effects of septal GABA receptor activation involve GABAergic septo-hippocampal projection neurons. Learn Mem. 2007;14(12):833–41. https://doi.org/10.1101/lm.809407.

    Article  Google Scholar 

  29. Mathew J, Soman S, Sadanandan J, Paulose CS. Decreased GABA receptor in the striatum and spatial recognition memory deficit in epileptic rats: effect of Bacopa monnieri and bacoside-A. J Ethnopharmacol. 2010;130:255–61.

    Article  CAS  Google Scholar 

  30. Mathew J, Gangadharan G, Kuruvilla KP, Paulose CS. Behavioral deficit and decreased GABA receptor functional regulation in the hippocampus of epileptic rats: effect of Bacopa monnieri. Neurochem Res. 2011;36:7–16.

    Article  CAS  Google Scholar 

  31. Mathew J, Balakrishnan S, Antony S, Abraham PM, Paulose CS. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and bacoside-A. J Biomed Sci. 2012;19:25.

    Article  CAS  Google Scholar 

  32. Mathew J, Paul J, Nandhu MS, Paulose CS. Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri. Fitoterapia. 2010;81:546–51.

    Article  CAS  Google Scholar 

  33. Mathew J, Kumar TP, Khan RS, Paulose CS. Behavioral deficit and decreased GABA receptor functional regulation in the cerebellum of epileptic rats: effect of Bacopa monnieri and bacoside A. Epilepsy Behav. 2010;17:441–7.

    Article  Google Scholar 

  34. Pandareesh MD, Anand T. Attenuation of smoke induced neuronal and physiological changes by bacoside rich extract in Wistar rats via down regulation of HO-1 and iNOS. Neurotoxicol. 2014;40:33–42.

    Article  CAS  Google Scholar 

  35. Hota SK, Barhwal K, Baitharu I, Prasad D, Singh SB, Ilavazhagan G. Bacopa monniera leaf extract ameliorates hypobaric hypoxia induced spatial memory impairment. Neurobiol Dis. 2009;34:23–39.

    Article  CAS  Google Scholar 

  36. Kamkaew N, Scholfield CN, Ingkaninan K, Maneesai P, Parkington HC, Tare M, et al. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. J Ethnopharmacol. 2011;137:790–5.

    Article  Google Scholar 

  37. Charles PD, Ambigapathy G, Geraldine P, Akbarsha MA, Rajan KE. Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation. J Ethnopharmacol. 2011;134:55–61.

    Article  Google Scholar 

  38. Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol. 2008;120:112–7.

    Article  Google Scholar 

  39. Pandareesh MD, Anand T. Neuromodulatory propensity of Bacopa monniera against scopolamine-induced cytotoxicity in pc12 cells via down-regulation of AChE and up-regulation of BDNF and muscarnic-1 receptor expression. Cell Mol Neurobiol. 2013;33:875–84.

    Article  CAS  Google Scholar 

  40. Pandareesh MD, Anand T, Khanum F. Cognition enhancing and neuromodulatory propensity of Bacopa monniera extract against scopolamine induced cognitive impairments in rat hippocampus. Neurochem Res. 2016;41:985–99.

    Article  CAS  Google Scholar 

  41. Kong SD, Lee J, Ramachandran S, Eliceiri BP, Shubayev VI, Lal R, et al. Magnetic targeting of nanoparticles across the intact blood-brain barrier. J Control Release. 2012;164:49–57.

    Article  CAS  Google Scholar 

  42. Li FY, Chaigne-Delalande B, Kanellopoulou C, Davis JC, Matthews HF, Douek DC, et al. Second messenger role for Mg2+ revealed by human T-cell immunodeficiency. Nature. 2011;475:471–6.

    Article  CAS  Google Scholar 

  43. Zhu D, Su Y, Fu B, Xu H. Magnesium reduces blood-brain barrier permeability and regulates amyloid-β transcytosis. Mol Neurobiol. 2018;55:7118–31.

    Article  CAS  Google Scholar 

  44. Agatonovic-Kustrin S, Chan CKY, Gegechkori V, Morton DW. Models for skin and brain penetration of major components from essential oils used in aromatherapy for dementia patients. J Biomol Struct Dyn. 2019;23:1–10.

    Google Scholar 

  45. Habbu P, Madagundi S, Kulkarni R, Jadav S, Vanakudri R, Kulkarni V. Preparation and evaluation of Bacopa-phospholipid complex for antiamnesic activity in rodents. Drug Invent Today. 2013;5:13–21.

    Article  CAS  Google Scholar 

  46. Amalraj A, Jacob J, Varma K, Kunnumakkara AB, Divya C, Gopi S. Acujoint™, a highly efficient formulation with natural bioactive compounds, exerts potent anti-arthritis effects in human osteoarthritis—a pilot randomized double blind clinical study compared to combination of glucosamine and chondroitin. J Herb Med. 2019;17-18:100276.

    Article  Google Scholar 

  47. Martin-Piñero MJ, Ramirez P, Muñoz J, Alfaro MC. Development of rosemary essential oil nanoemulsions using a wheat biomass-derived surfactant. Colloids Surf B. 2019;173:486–92.

    Article  CAS  Google Scholar 

  48. Qu L, Xu H, Jia W, Jiang H, Xie J. Rosmarinic acid protects against MPTP-induced toxicity and inhibits iron-induced α-synuclein aggregation. Neuropharmacol. 2019;144:291–300.

    Article  CAS  Google Scholar 

  49. Kuo CF, Su JD, Chiu CH, Peng CC, Chang CH, Sung TY, et al. Anti-inflammatory effects of supercritical carbon dioxide extract and its isolated carnosic acid from Rosmarinus officinalis leaves. J Agric Food Chem. 2011;59:3674–85.

    Article  CAS  Google Scholar 

  50. Liang X, Yu H, Hu W, Zhang L, Yang W, Jin C, et al. Protective effect of carnosic acid and its semisynthetic derivatives against H2O2-induced neurotoxicity. Phytochem Lett. 2018;27:82–6.

    Article  CAS  Google Scholar 

  51. Pertino MW, Theoduloz C, Butassi E, Zacchino S, Schmeda-Hirschmann G. Synthesis, antiproliferative and antifungal activities of 1,2,3-triazole-substituted carnosic acid and carnosol derivatives. Molecules. 2015;20:8666–86.

    Article  CAS  Google Scholar 

  52. Pertino MW, Theoduloz C, Rodríguez JA, Yáñez T, Lazo V, Schmeda-Hirschmann G. Gastroprotective effect of carnosic acid gamma-lactone derivatives. J Nat Prod. 2010;73:639–43.

    Article  CAS  Google Scholar 

  53. Tamaki Y, Tabuchi T, Takahashi T, Kosaka K, Satoh T. Activated glutathione metabolism participates in protective effects of carnosic acid against oxidative stress in neuronal HT22 cells. Planta Med. 2010;76:683–8.

    Article  CAS  Google Scholar 

  54. Kosaka K, Mimura J, Itoh K, Satoh T, Shimojo Y, Kitajima C, et al. Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells. J Biochem. 2010;147:73–81.

    Article  CAS  Google Scholar 

  55. Chen JH, Ou HP, Lin CY, Lin FJ, Wu CR, Chang SW, et al. Carnosic acid prevents 6-hydroxydopamine-induced cell death in SH-SY5Y cells via mediation of glutathione synthesis. Chem Res Toxicol. 2012;25:1893–901.

    Article  CAS  Google Scholar 

  56. Lin CY, Fu RH, Chou RH, Chen JH, Wu CR, Chang SW, et al. Inhibition of JNK by pi class of glutathione S-transferase through PKA/CREB pathway is associated with carnosic acid protection against 6-hydroxydopamine-induced apoptosis. Food Chem Toxicol. 2013;103:194–202.

    Article  CAS  Google Scholar 

  57. Lin CY, Chen JH, Fu RH, Tsai CW. Induction of PI form of glutathione S-transferase by carnosic acid is mediated through PI3K/Akt/NF-κB pathway and protects against neurotoxicity. Chem Res Toxicol. 2014;27:1958–66.

    Article  CAS  Google Scholar 

  58. Lin CY, Tsai CW, Tsai CW. Carnosic acid protects SH-SY5Y cells against 6-hydroxydopamine-induced cell death through upregulation of parkin pathway. Neuropharmacol. 2016;110:109–17.

    Article  CAS  Google Scholar 

  59. Fu RH, Huang LC, Lin CY, Tsai CW. Modulation of ARTS and XIAP by Parkin is associated with carnosic acid protects SH-SY5Y cells against 6-hydroxydopamine-induced apoptosis. Mol Neurobiol. 2018;55:1786–94.

    Article  CAS  Google Scholar 

  60. Wu CR, Tsai CW, Chang SW, Lin CY, Huang LC, Tsai CW. Carnosic acid protects against 6-hydroxydopamine-induced neurotoxicity in in vivo and in vitro model of Parkinson’s disease: involvement of antioxidative enzymes induction. Chem Boil Interact. 2015;225:40–6.

    Article  CAS  Google Scholar 

  61. Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem Toxicol. 2008;46:409–20.

    Article  CAS  Google Scholar 

  62. Lim S, Moon M, Oh H, Kim HG, Kim SY, Oh MS. Ginger improves cognitive function via NGF-induced ERK/CREB activation in the hippocampus of the mouse. J Nutr Biochem. 2014;25:1058–65.

    Article  CAS  Google Scholar 

  63. Ridaura V, Belkaid Y. Gut microbiota: the link to your second brain. Cell. 2015;161:193–4.

    Article  CAS  Google Scholar 

  64. Ochoa-Repáraz J, Kasper LK. The second brain: is the gut microbiota a link between obesity and central nervous system disorders? Curr Obes Rep. 2016;5:51–64.

    Article  Google Scholar 

  65. Martin CR, Osadchiy V, Kalani A, Mayer EA. The brain-gut-microbiome axis. Cell Mol Gastroenterol Hepatol. 2018;6:133–48.

    Article  Google Scholar 

  66. Keita AV, Soderholm JD. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil. 2010;22:718–33.

    Article  CAS  Google Scholar 

  67. Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol. 2008;59:251–62.

    Google Scholar 

  68. Romijn JA, Corssmit EP, Havekes LM, Pijl H. Gut-brain axis. Curr Opin Clin Nutr Metab Care. 2008;11:518–21.

    Article  CAS  Google Scholar 

  69. Mercer JG. Editorial for Full4Health special issue of ‘Peptides’: peptides in the food-gut-brain axis and roles in hunger and satiety. Peptides. 2016;77:1–2.

    Article  CAS  Google Scholar 

  70. Liu Q, Ma Q, Liu Y, Li X, Jiang Y, Yan Z, et al. Effect of Xiaoyao San on the brain-gut axis in rats after chronic immobilization stress. J Tradit Chin Med. 2017;4:184–94.

    Google Scholar 

  71. Zhong LY, Heng-li T, Zhen-hao M, Huan-huan X, Qian-feng GJ. The common features and mechanisms of ginger juice processing technology based on the composition and gastrointestinal effects of Chinese herbs. Phys Chem Biophys. 2017;7:2.

    Google Scholar 

  72. Mansour MS, Ni YM, Roberts AL, Kelleman M, Choudhury AR, St-Onge MP. Ginger consumption enhances the thermic effect of food and promotes feelings of satiety without affecting metabolic and hormonal parameters in overweight men: a pilot study. Metab Clin Exp. 2012;61:1347–52.

    Article  CAS  Google Scholar 

  73. Inatomi N, Sato F, Marui S, Itoh Z, Omura S. Vagus-dependent and vagus-independent mechanisms of action of the erythromycin derivative EM574 and motilin in dogs. Jpn J Pharmacol. 1996;71:29–38.

    Article  CAS  Google Scholar 

  74. Howick K, Griffin BT, Cryan JF, Schellekens H. From belly to brain: targeting the ghrelin receptor in appetite and food intake regulation. Int J Mol Sci. 2017;18:273.

    Article  CAS  Google Scholar 

  75. Koshal P, Jamwal S, Kumar P. Glucagon-like peptide-1 (GLP-1) and neurotransmitters signaling in epilepsy: an insight review. Neuropharmacol. 2018;136:271–9.

    Article  CAS  Google Scholar 

  76. Eichenbaum H. The hippocampus and declarative memory: cognitive mechanisms and neural codes. Behav Brain Res. 2001;127:199–207.

    Article  CAS  Google Scholar 

  77. Ayaz M, Sadiq A, Junaid M, Ullah F, Subhan F, Ahmed J. Neuroprotective and anti-aging potentials of essential oils from aromatic and medicinal plants. Front Aging Neurosci. 2017;9:168.

    Article  CAS  Google Scholar 

  78. Farr SA, Niehoff ML, Ceddia MA, Herrlinger KA, Lewis BJ, Feng S, et al. Effect of botanical extracts containing carnosic acid or rosmarinic acid on learning and memory in SAMP8 mice. Physiol Behav. 2016;165:328–38.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully thank the management of Plant Lipids Private Limited and Aurea Biolabs Private Limited, Cochin, India, for their support and encouragement. We wish to express our appreciation to our laboratory members for their active help and cooperation.

Author information

Authors and Affiliations

  1. R&D Centre, Aurea Biolabs (P) Ltd, Kolenchery, Cochin, Kerala, 682311, India

    Augustine Amalraj, Nimisha Pulikkal Sukumaran, Akhila Nair & Sreeraj Gopi

Authors
  1. Augustine Amalraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nimisha Pulikkal Sukumaran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Akhila Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sreeraj Gopi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sreeraj Gopi.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Amalraj, A., Sukumaran, N.P., Nair, A. et al. Preparation of a Unique Bioavailable Bacoside Formulation (Cognique®) Using Polar-Nonpolar-Sandwich (PNS) Technology and Its Characterization, In Vitro Release Study, and Proposed Mechanism of Action. Regen. Eng. Transl. Med. 7, 379–392 (2021). https://doi.org/10.1007/s40883-020-00162-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40883-020-00162-2

Keywords

Search

Navigation