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Novel Drug Delivery Systems for Herbal Antidepressants

  • Vandita KakkarEmail author
  • Nancy Modgill
  • Manoj Kumar
Chapter

Abstract

Depression, a potentially life-threatening mood disorder, affects one in six persons in the United States, or approximately 17.6 million Americans each year. It is one of the top ten causes of morbidity and mortality worldwide as reported by the World Health Organization. Depressed patients are more likely to develop secondary diseases like type 2 diabetes and cardiovascular disease. Furthermore, depression is the third leading cause of global disease burden, accounting for 4.3 % of the total disability-adjusted life years. Predictions based on current exponential rise may assign it to be the leading cause of disease burden by the year 2030.

Despite advances in the treatment of depression with selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), there continue to be several unmet clinical needs with respect to both the efficacy and the persisting side effects. Herbal drugs with evident antidepressant activity are purported to possess lower risk of precipitating side effects and can be explored as novel drug candidates. Though they find ample space to broaden their therapeutic segment at lab scale, their translation to clinics often has resulted in a failure. The latter is assigned to their compromised bioavailability across the blood–brain barrier (BBB) and attributed to their poor solubility and permeability, photodegradation and lower available systemic concentrations. All these concerns call for the development of novel drug delivery systems (NDDS), which include oral gastro-resistant formulations; transdermal delivery; nasal therapies; nanotechnology-based products, i.e. polymeric and lipidic nanoparticles; self-emulsifying novel drug delivery systems; liposomes; nanostructured lipid carriers; to nanodevices. The commercialisation of the herbal NDDS products especially the nanotech-based delivery system, is governed by stringent regulations, though a few products which fall into the category of modified conventional therapies may get approvals from FDA.

This chapter elaborates the need for developing the NDDS for herbal antidepressants (AD). Furthermore, an extensive review of the work done by the researchers around the globe and the constraints are also presented herewith. The regulations governing the approval of product for commercialisation and the future direction for these herbal antidepressants are also discussed.

Keywords

Antidepressants Bioavailability Herbals FDA Novel delivery system 

Notes

Disclosure

The author reports no conflict of interest in this work.

References

  1. Abdelrahman FE et al. Investigating the cubosomal ability for transnasal brain targeting: In vitro optimization, ex vivo permeation and in vivo biodistribution. Int J Pharm. 2015;490(1–2):281–91. Available at: http://www.sciencedirect.com/science/article/pii/S0378517315004937.Google Scholar
  2. Alam MI et al. Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain. J Psychiatr Res. 2012;46(9):1133–8.CrossRefPubMedGoogle Scholar
  3. Alves-Rodrigues A, Shao A. The science behind lutein. Toxicol Lett. 2004;150(1):57–83.CrossRefPubMedGoogle Scholar
  4. Anton N, Jakhmola A, Vandamme TF. Trojan microparticles for drug delivery. Pharmaceutics. 2012;4(1):1–25. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3834908/.Google Scholar
  5. Appleton J. Lavender oil for anxiety and depression. Nat Med J. 2012;4(2).Google Scholar
  6. Baker CB et al. Quantitative analysis of sponsorship bias in economic studies of antidepressants. Br J Psychiatry J Ment Sci. 2003;183:498–506.CrossRefGoogle Scholar
  7. Bernstein PS et al. Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye. Exp Eye Res. 2001;72(3):215–23.CrossRefPubMedGoogle Scholar
  8. Braithwaite MC et al. Nutraceutical-based therapeutics and formulation strategies augmenting their efficiency to complement modern medicine: an overview. J Funct Foods. 2014;6:82–99.CrossRefGoogle Scholar
  9. Butterweck V, Schmidt M. St. John’s wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr. 2007;157(13-14):356–61.CrossRefPubMedGoogle Scholar
  10. Camfield DA, Sarris J, Berk M. Nutraceuticals in the treatment of obsessive compulsive disorder (OCD): a review of mechanistic and clinical evidence. Prog Neuro-Psychopharmacol Biol Psychiatry. 2011;35(4):887–95.CrossRefGoogle Scholar
  11. Dhiman A, Nanda A, Ahmad S. Novel herbal drug delivery system ( NHDDS ): the need of hour. IPCBEE. 2012;49:171–5.Google Scholar
  12. Duman RS. Depression: a case of neuronal life and death? Biol Psychiatry. 2004;56(3):140–5.CrossRefPubMedGoogle Scholar
  13. Duman RS, Heninger GR, Nestler EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry. 1997;54(7):597–606.CrossRefPubMedGoogle Scholar
  14. EMEA. Note for guidance specifications: test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. Reproduction, 2(November 1999); 2006. p. 1–15. Available at: http://www.ncbi.nlm.nih.gov/pubmed/22167572.
  15. Facchini PJ. Alkaloid biosynthesis in plants: biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Annu Rev Plant Physiol Plant Mol Biol. 2001;52:29–66.CrossRefPubMedGoogle Scholar
  16. FDA. Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics Guidance for Industry Analytical Procedures and Methods Validation for Drugs and Biologics., (February), 2014; p. 18. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM386366.pdf [Accessed 25 Aug 2015].
  17. Fowler A et al. A nonradioactive high-throughput/high-content assay for measurement of the human serotonin reuptake transporter function in vitro. J Biomol Screen. 2006;11(8):1027–34.CrossRefPubMedGoogle Scholar
  18. Guest JA, Grant RS. Effects of dietary derived antioxidants on the central nervous system. Int J Nutr Pharmacol Neurol Dis. 2012;2(3):195–7.Google Scholar
  19. Hausenblas HA et al. Meta-analysis Saffron ( Crocus sativus L.) and major depressive disorder: a meta-analysis of randomized clinical trials. J Integr Med. 2013;11(6):377–83.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Holstein SA, Hohl RJ. Isoprenoids: remarkable diversity of form and function. Lipids. 2004;39(4):293–309.CrossRefPubMedGoogle Scholar
  21. Illum L. Is nose-to-brain transport of drugs in man a reality? J Pharm Pharmacol. 2004;56(1):3–17.CrossRefPubMedGoogle Scholar
  22. Illum L. Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci. 2000;11(1):1–18.CrossRefPubMedGoogle Scholar
  23. Jain KK. Nanobiotechnology-based strategies for crossing the blood brain barrier. Nanomedicine. 2012;7(8):1225–33.CrossRefPubMedGoogle Scholar
  24. Jaworska A. A comparison between adsorption mechanism of tricyclic antidepressants on silver nanoparticles and binding modes on receptors. J Colloid Interface Sci. 2014;431:117–24.CrossRefPubMedGoogle Scholar
  25. Jerome S et al. Herbal medicine for depression, anxiety and insomnia: a review of psychopharmacology and clinical evidence. Eur Neuropsychopharmacol. 2011;21:841–60.CrossRefGoogle Scholar
  26. Jessen L, Kovalick LJ, Azzaro AJ. The selegiline transdermal system (Emsam): a therapeutic option for the treatment of major depressive disorder. Pharm Therapeut. 2008;33(4):212–46. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730099/.
  27. De Jong WH, Borm PJA. Drug delivery and nanoparticles: applications and hazards. Int J Nanomedicine. 2008;3(2):133–49. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527668/.
  28. Joshi M, Patravale V. Formulation and evaluation of nanostructured lipid carrier (NLC)-based gel of Valdecoxib. Drug Dev Ind Pharm. 2006;32(8):911–8.CrossRefPubMedGoogle Scholar
  29. Kakkar V, Kaur IP. Antidepressant activity of curcumin loaded solid lipid nanoparticles (C-SLNs) in mice. Am J Pharm Res. 2012;2(3).Google Scholar
  30. Kateb B et al. Nanoplatforms for constructing new approaches to cancer treatment, imaging, and drug delivery: what should be the policy? NeuroImage. 2011;54 Suppl 1:S106–24. Available at: http://www.sciencedirect.com/science/article/pii/S1053811910001448 [Accessed 4 May 2015].
  31. Kesarwani K, Gupta R. Bioavailability enhancers of herbal origin: An overview. Asian Pac J Trop Biomed. 2013;3(4):253–66.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Kukongviriyapan U et al. Preventive and therapeutic effects of quercetin on lipopolysaccharide-induced oxidative stress and vascular dysfunction in mice. Can J Physiol Pharmacol. 2012;90(10):1345–53.CrossRefPubMedGoogle Scholar
  33. Kumar V. Potential medicinal plants for CNS disorders: an overview. Phytother Res. 2006;20(12):1023–35.CrossRefPubMedGoogle Scholar
  34. Lee B-H, Kim Y-K. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry Investig. 2010;7(4):231–5. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3022308/.Google Scholar
  35. Litt B. Nanodevices to Treat Neurological Diseases. Brain Research Foundation; 2013. Available at: http://www.thebrf.org/Pages/Topic?id=1426 [Accessed 25 Aug 2015].
  36. Ma P, Mumper RJ. Paclitaxel nano-delivery systems: a comprehensive review. Journal of nanomedicine nanotechnology. 2013;4(2):1000164. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3806207/.
  37. Manach C et al. Polyphenols: food sources and bioavailability 1,2. Am J Clin Nutr. 2004;79:727–47.PubMedGoogle Scholar
  38. Marcus M et al. DEPRESSION: A Global Public Health Concern. WHO Department of Mental Health and Substance Abuse; 2012. p. 6–8. Available at: http://www.who.int/mental_health/management/depression/who_paper_depression_wfmh_2012.pdf [Accessed 28 Aug 2015].
  39. Mathers C, Boerma T and Fat DM. The global burden of disease; 2004. p. 1–160. Available at: http://www.who.int/healthinfo/global_burden_disease/2004_report_update/en/ [Accessed 28 Aug 2015].
  40. Mattson MP. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008;1144:97–112. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614307/.Google Scholar
  41. Meijer WEE et al. Association of risk of abnormal bleeding with degree of serotonin reuptake inhibition by antidepressants. Arch Intern Med. 2004;164(21):2367–70.CrossRefPubMedGoogle Scholar
  42. Mercola J. 10 Antidepressant Alternatives Proven to Work; 2009. Available at: Mercola.com [Accessed 10 Aug 2015].Google Scholar
  43. MHDaily. Nanotechnology for depression: the futuristic potential of nanopsychiatry. Mental Health Blog; 2015. Available at: http://mentalhealthdaily.com/2015/08/31/nanotechnology-for-depression-the-futuristic-potential-of-nanopsychiatry/ [Accessed 25 Sept 2015].
  44. O’Leary O, Dinan T, Cryan J. Faster, better, stronger_ towards new antidepressant therapeutic strategies. Eur J Pharmacol. 2015;753:32–50.CrossRefPubMedGoogle Scholar
  45. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxidative Med Cell Longev. 2009;2(5):270–8. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835915/.Google Scholar
  46. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009;4(3):198–219.CrossRefPubMedGoogle Scholar
  47. Parletta N, Milte CM, Meyer BJ. Nutritional modulation of cognitive function and mental health. J Nutr Biochem. 2013;24(5):725–43.CrossRefPubMedGoogle Scholar
  48. Pattanayak RD, Sagar R. Depressive disorders in indian context: a review and clinical update for physicians. Journal of the Association of Physicians of India. 2014;62:827–32.PubMedGoogle Scholar
  49. Pick M. Antidepressants and natural alternatives. Emotions, anxiety and mood. 2015. Available at: https://www.womentowomen.com/emotions-anxiety-mood/antidepressants-alternatives/.
  50. Pierce G. Should we clean up the reputation of “ dirty drugs ”? Can J Physiol Pharmacol. 2012;1334(September):1333–4.CrossRefGoogle Scholar
  51. Pires AF et al. The role of endothelium in the vasorelaxant effects of the essential oil of Ocimum gratissimum in aorta and mesenteric vascular bed of rats. Can J Physiol Pharmacol. 2012;90(10):1380–5.CrossRefPubMedGoogle Scholar
  52. Prakash D et al. Effect of nanohypericum (Hypericum perforatum gold nanoparticles) treatment on restraint stressinduced behavioral and biochemical alteration in male albino mice. Pharmacognosy Res. 2010;2(6):330–4.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Priprem A et al. Antidepressant and cognitive activities of intranasal piperine-encapsulated liposomes. Adv Biosci Biotechnol. 2011;02(02):108–16.CrossRefGoogle Scholar
  54. Priprem A et al. Anxiety and cognitive effects of quercetin liposomes in rats. Nanomedicine. 2008;4(1):70–8.PubMedGoogle Scholar
  55. Rabanel J-M et al. Effect of polymer architecture on curcumin encapsulation and release from PEGylated polymer nanoparticles: Toward a drug delivery nano-platform to the CNS. European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V; 2015.Google Scholar
  56. Rahman A et al. The neglected “m” in MCH programmes-why mental health of mothers is important for child nutrition. Tropical Med Int Health. 2008;13(4):579–83.CrossRefGoogle Scholar
  57. Re F et al. Functionalization of liposomes with ApoE-derived peptides at different density affects cellular uptake and drug transport across a blood-brain barrier model. Nanomedicine. 2011;7(5):551–9.PubMedGoogle Scholar
  58. Roy-Byrne P. Herbal Psychotropic Medications: Promises and Pitfalls. Psychiatry; 1998. Available at: http://www.jwatch.org/jp199811010000019/1998/11/01/herbal-psychotropic-medications-promises-and [Accessed 20 Aug 2015].
  59. Sahu AN. Nanotechnology in herbal medicines and cosmetics. Int J Ayurveda Pharm. 2013;4(3):472–4.CrossRefGoogle Scholar
  60. Saraf S. Fitoterapia applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010;81(7):680–9.CrossRefPubMedGoogle Scholar
  61. Sarris J et al. The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum. Psychopharmacology. 2009;205(3):399–407.CrossRefPubMedGoogle Scholar
  62. Sarris J, Kavanagh DJ, Byrne G. Adjuvant use of nutritional and herbal medicines with antidepressants, mood stabilizers and benzodiazepines. J Psychiatr Res. 2010;44(1):32–41.CrossRefPubMedGoogle Scholar
  63. Sayyah M, Sayyah M, Kamalinejad M. A preliminary randomized double blind clinical trial on the efficacy of aqueous extract of Echium amoenum in the treatment of mild to moderate major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(1):166–9.Google Scholar
  64. Scalbert A et al. Dietary polyphenols and the prevention of diseases. Crit Rev Food Sci Nutr. 2005;45(4):287–306.CrossRefPubMedGoogle Scholar
  65. Spinella M. The Psychopharmacology of Herbal Medicine Plant Drugs That Alter Mind Brain and Behavior by Marcello Spinella Information 6586th ed., London, England: Mit Press; 2001. Available at: https://books.google.co.in/books?id=jZeaRiIFbhsC&dq=The+Psychopharmacology+of+Herbal+Medicine+Plant+Drugs+That+Alter+Mind+Brain+and+Behavior+by+Marcello+Spinella+Information&source=gbs_navlinks_s.
  66. Stevens JR et al. The use of transdermal therapeutic systems in psychiatric care: a primer on patches. Psychosomatics. 2015;56(5):423–44. Available at: http://www.sciencedirect.com/science/article/pii/S0033318215000602.Google Scholar
  67. Tamjidi F et al. Nanostructured lipid carriers ( NLC ): A potential delivery system for bioactive food molecules. Innovat Food Sci Emerg Tech. 2013;19:29–43.CrossRefGoogle Scholar
  68. Thakkar HP, Patel AA, Chauhan NP. Intranasal mucoadhesive microemulsion of mirtazapine: pharmacokinetic and pharmacodynamic studies. Asian J Pharmaceut. 2013;7(1):36–42.CrossRefGoogle Scholar
  69. Tiwari G et al. Drug delivery systems: an updated review. Int J Pharmaceut Investig. 2012;2(1):2–11. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3465154/.Google Scholar
  70. Torchilin V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm. 2011;71(3):431–44.CrossRefGoogle Scholar
  71. Upadhyay RK. Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Res Int. 2014;2014:869269. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127280/.Google Scholar
  72. Uttara B et al. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65–74. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724665/.Google Scholar
  73. Vauzour D. Dietary polyphenols as modulators of brain functions: biological actions and molecular mechanisms underpinning their beneficial effects. Oxidative Medicine and Cellular Longevity; 2012. p. 1–16.Google Scholar
  74. Vijaya R, Ruckmani K. In vitro and In vivo characterization of the transdermal delivery of sertraline hydrochloride Films. DARU. 2011;19(6):424–32. Available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436079/.
  75. Walle T et al. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32(12):1377–82.CrossRefPubMedGoogle Scholar
  76. Wang R and Xu Y. Phytochemicals as antidepressants: the involvement of serotonin receptor function, stress resistance and neurogenesis. In: Kuang PH, Editor. Recent advances in theories and practice of Chinese medicine; 2012. p. 473–492. Available at: www.intechopen.com.Google Scholar
  77. Wattanathorn J et al. quercetin.pdf. Am J Agr Biol Sci. 2007;2(1):31–5.CrossRefGoogle Scholar
  78. Welch H and Hasbun R. Chapter 3 - Lumbar puncture and cerebrospinal fluid analysis. In Vinken PJ and Bruyn GW, Editors. Handbook of Clinical Neurology. Department of Medicine, Section of Infectious Diseases, University of Texas Medical School, Houston, TX, USA: North-Holland Publishing Company; 2010. p. 31–49. Available at: http://www.sciencedirect.com/science/article/pii/S0072975209960031.Google Scholar
  79. WFMH. Depression: A Global Crisis. World Fedaration of Mental Health; 2012. p. 1–32. Available at: http://www.who.int/mental_health/management/depression/wfmh_paper_depression_wmhd_2012.pdf [Accessed 12 Sept 2015].
  80. WHO. Annex 2: The International Pharmacopoeia: revised concepts and future perspectives; 2003. 1(908): 22–25. Available at: http://www.who.int/medicines/areas/quality_safety/quality_assurance/PhIntRevisedConceptsFuturePerspectivesTRS908Annex2.pdf?ua=1 [Accessed 10 Oct 2015].
  81. WHO. Good practices for pharmaceutical quality control laboratories; 2010. (957): 81–129. Available at: http://apps.who.int/prequal/info_general/documents/trs957/gpcl_trs957_annex1.pdf [Accessed 10 Oct 2015].
  82. WHO. Suicide Prevention Across the Globe: Strengthening Protective Factors and Instilling Hope. International Association for Suicide Prevention; 2012. p. 1–3. Available at: www.iasp.info/wspd [Accessed 18 Oct 2015].
  83. WHO. WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems; 2004. p. 1–82. Available at: http://apps.who.int/medicinedocs/documents/s7148e/s7148e.pdf [Accessed 10 Oct 2015].
  84. Williamson EM. Synergy and other interactions in phytomedicines. Phytomedicine. 2001;8(5):401–9.CrossRefPubMedGoogle Scholar
  85. Wu L et al. Research article a self-microemulsifying drug delivery system ( SMEDDS ) for a Novel Medicative Compound Against Depression: a Preparation and Bioavailability Study in Rats. American Association of Pharmaceutical Scientists PharmSciTech; 2015. (13).Google Scholar
  86. Yin D et al. Increase in brain tumor permeability in glioma-bearing rats with nitric oxide donors. Clin Cancer Res. 2008;14(12):4002–9.CrossRefPubMedGoogle Scholar
  87. Zhu W et al. Green tea polyphenols produce antidepressant-like effects in adult mice. Pharmacol Res. 2012;65:74–80.CrossRefPubMedGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia
  2. 2.Advanced Drug Delivery Research, R&DPancea Biotec LimitedLalruIndia

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