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Design and Optimization of Nanophytosomes Containing Mucuna prureins Hydroalcoholic Extract for Enhancement of Antidepressant Activity

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Abstract

Purpose

In this study, the herbal formulation containing nanophytosomes of Mucuna prureins extract (MPE) was engineered to ameliorate its rate of drug release, in vivo antidepressant profile, and stability.

Method

The Mucuna prureins nanophytosomes (MPP) were designed by using a full factorial design approach, taking into consideration various variables that could give optimized formulation. Then, pure extract and optimized formulation showing higher entrapment efficiency were studied for in vitro dissolution and in vivo antidepressant activity in depression models like forced swimming test (FST) and tail suspension test (TST) in Swiss albino mice. The physicochemical characterization was carried out using particle size analysis and zeta potential, Fourier transformation infrared spectroscopy, differential scanning calorimetry, proton nuclear magnetic resonance, powder X-ray diffractometer, scanning electron microscopy, and solubility studies. Moreover, the stability of nanophytosomes was assessed by subjecting optimized formulation to freeze–thaw cycle stability testing and calculating entrapment efficiency at the end of the cycle.

Results

PXRD and SEM revealed a decrease in the crystalline nature of nanophytosomes. 1H NMR, DSC, and FTIR asserted the formation of the phyto-phospholipids complex. The rate and extent of dissolution were also found enhanced and sustained in nanophytosomes as compared to pure extract. In vivo antidepressant activity depicted a significant reduction of immobility in mice treated with nanophytosomes as compared to those treated with the pure extract. Moreover, optimized formulation was found stable as entrapment efficiency values were not reduced significantly.

Conclusion

Thus, nanophytosomes drug delivery could be the best strategy to improve physicochemical properties of extract and thus could be exploited for the extracts having poor solubility, poor permeability, and poor stability.

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References

  1. Ravikumar P, Jeyam M. Antidepressant activity and HPTLC fingerprinting of stearic acid in different days of wheat seedlings. Grain & Oil Science and Technology. 2019;2(1):6–10.

    Article  Google Scholar 

  2. Nestler EJ, Barrot M, DiLeone RJ, Eisch AJ, Gold SJ, Monteggia LM. Neurobiology of depression. Neuron. 2002;34(1):13–25.

    Article  CAS  PubMed  Google Scholar 

  3. Gillespie CF, Nemeroff CB. Hypercortisolemia and depression. Psychosom Med. 2005;67:S26–8.

    Article  PubMed  Google Scholar 

  4. Dereli FTG, Ilhan M, Sobarzo-Sánchez E, Akkol EK. The investigation of the potential antidepressant-like activity of Xanthium orientale subsp. italicum (Moretti) Greuter in rodents. J Ethnopharmacol. 2020;258:112914.

  5. Yemez B, Alptekin K. Depression etiology. World of Psychiatry. 1998;2(1):21–5.

    Google Scholar 

  6. Singh GK, Garabadu D, Muruganandam A, Joshi VK, Krishnamurthy S. Antidepressant activity of Asparagus racemosus in rodent models. Pharmacol Biochem Behav. 2009;91(3):283–90.

    Article  CAS  PubMed  Google Scholar 

  7. Huprich SK. What should become of depressive personality disorder in DSM-V? Harv Rev Psychiatry. 2009;17(1):41–59.

    Article  PubMed  Google Scholar 

  8. Schmidt HD, Shelton RC, Duman RS. Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology. 2011;36(12):2375–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gold PW, Goodwin FK, Chrousos GP. Clinical and biochemical manifestations of depression. N Engl J Med. 1988;319(7):413–20.

    Article  CAS  PubMed  Google Scholar 

  10. Randrup A. Mania, depression, and brain dopamine. 1975.

  11. Muscat R, Papp M, Willner P. Antidepressant-like effects of dopamine agonists in an animal model of depression. Biol Psychiat. 1992;31(9):937–46.

    Article  CAS  PubMed  Google Scholar 

  12. Rana DG, Galani VJ. Dopamine mediated antidepressant effect of Mucuna pruriens seeds in various experimental models of depression. Ayu. 2014;35(1):90.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Bet PM, Hugtenburg JG, Penninx BW, Hoogendijk WJ. Side effects of antidepressants during long-term use in a naturalistic setting. Eur Neuropsychopharmacol. 2013;23(11):1443–51.

    Article  CAS  PubMed  Google Scholar 

  14. Zhang Z-J. Therapeutic effects of herbal extracts and constituents in animal models of psychiatric disorders. Life Sci. 2004;75(14):1659–99.

    Article  CAS  PubMed  Google Scholar 

  15. Lampariello LR, Cortelazzo A, Guerranti R, Sticozzi C, Valacchi G. The magic velvet bean of Mucuna pruriens. J Tradit Complement Med. 2012;2(4):331–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Nweze NE, Ezema C, Ezema AS, Eze JI, Ezema WS. Toxicity and nutritional studies on Mucuna pruriens leaves from Nsukka, South-Eastern Nigeria. Comp Clin Pathol. 2017;26(3):569.

    Article  CAS  Google Scholar 

  17. Amin KY, Khan M, Zillur-Rehman S, Khan N. Sexual function improving effect of Mucuna pruriens in sexually normal male rats. Fitoterapia (Milano). 1996;67(1):53–8.

  18. Gupta M, Chakrabarti S, Bhattacharya S, Rath N. Anti-epileptic and anti-cancer activity of some indigenous plants. Indian J Physiol Allied Sciences. 1997;51:53–6.

    Google Scholar 

  19. Sathiyanarayanan L, Arulmozhi S. Mucuna pruriens Linn.-A comprehensive review. Pharmacogn Rev. 2007;1(1).

  20. Rajeshwar Y, Kumar GS, Gupta M, Mazumder UK. Studies on in vitro antioxidant activities of methanol extract of Mucuna pruriens (Fabaceae) seeds. Eur Bull Drug Res. 2005;13(1):31–9.

    Google Scholar 

  21. Jalalpure S, Alagawadi K, Mahajanashetti C, Shah B, Singh V, Patil J. In vitro anthelmintic property of various seed oils against Pheritima posthuma. Indian J Pharm Sci. 2007;69(1):158.

    Article  Google Scholar 

  22. Guerranti R, Aguiyi JC, Errico E, Pagani R, Marinello E. Effects of Mucuna pruriens extract on activation of prothrombin by Echis carinatus venom. J Ethnopharmacol. 2001;75(2–3):175–80.

    Article  CAS  PubMed  Google Scholar 

  23. Misra L, Wagner H. Alkaloidal constituents of Mucuna pruriens seeds. Phytochemistry. 2004;65(18):2565–7.

    Article  CAS  PubMed  Google Scholar 

  24. Hishika R, Shastry S, Shinde S, Guptal S. Preliminary phytochemical and anti-inflammatory activity of seeds of Mucuna pruriens. Indian J pharmacol. 1981;13(1):97–8.

    Google Scholar 

  25. Siddhuraju P, Becker K. Rapid reversed-phase high performance liquid chromatographic method for the quantification of L-Dopa (L-3, 4-dihydroxyphenylalanine), non-methylated and methylated tetrahydroisoquinoline compounds from Mucuna beans. Food Chem. 2001;72(3):389–94.

    Article  CAS  Google Scholar 

  26. Tripathi YB, Upadhyay AK. Antioxidant property of Mucuna pruriens Linn. Curr Sci. 2001;80(11):1377–8.

    Google Scholar 

  27. Kemp K, Griffiths J, Campbell S, Lovell K. An exploration of the follow-up up needs of patients with inflammatory bowel disease. J Crohns Colitis. 2013;7(9):e386–95.

    Article  PubMed  Google Scholar 

  28. Minaei A, Sabzichi M, Ramezani F, Hamishehkar H, Samadi N. Co-delivery with nano-quercetin enhances doxorubicin-mediated cytotoxicity against MCF-7 cells. Mol Biol Rep. 2016;43(2):99–105.

    Article  CAS  PubMed  Google Scholar 

  29. Singh RP, Narke R. Preparation and evaluation of phytosome of lawsone. Int J Pharm Sci Res. 2015;6(12):5217.

    CAS  Google Scholar 

  30. Mattos BD, Tardy BL, Magalhães WL, Rojas OJ. Controlled release for crop and wood protection: Recent progress toward sustainable and safe nanostructured biocidal systems. J Control Release. 2017;262:139–50.

    Article  CAS  PubMed  Google Scholar 

  31. Maiti K, Mukherjee K, Gantait A, Saha BP, Mukherjee PK. Curcumin–phospholipid complex: preparation, therapeutic evaluation and pharmacokinetic study in rats. Int J Pharm. 2007;330(1–2):155–63.

    Article  CAS  PubMed  Google Scholar 

  32. Maryana W, Rachmawati H, Mudhakir D. Formation of phytosome containing silymarin using thin layer-hydration technique aimed for oral delivery. Materials today: proceedings. 2016;3(3):855–66.

    Google Scholar 

  33. Saoji SD, Raut NA, Dhore PW, Borkar CD, Popielarczyk M, Dave VS. Preparation and evaluation of phospholipid-based complex of standardized centella extract (SCE) for the enhanced delivery of phytoconstituents. AAPS J. 2016;18(1):102–14.

    Article  CAS  PubMed  Google Scholar 

  34. Maiti K, Mukherjee K, Murugan V, Saha BP, Mukherjee PK. Exploring the effect of hesperetin–HSPC complex—a novel drug delivery system on the in vitro release, therapeutic efficacy and pharmacokinetics. AAPS PharmSciTech. 2009;10(3):943–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266(5604):730–2.

    Article  CAS  PubMed  Google Scholar 

  36. Elsheikh MA, Elnaggar YS, Gohar EY, Abdallah OY. Nanoemulsion liquid preconcentrates for raloxifene hydrochloride: optimization and in vivo appraisal. Int J Nanomed. 2012;7:3787.

    CAS  Google Scholar 

  37. Yi H, Yang Z, Yongfang Z. The purification and the identification of lecithin and its application. Amino Acids and Biotic Resources. 2001;23(2):28–31.

    Google Scholar 

  38. Shivanand P, Kinjal P. Phytosomes: technical revolution in phytomedicine. Int J Pharmtech Res. 2010;2(1):627–31.

    Google Scholar 

  39. Yanyu X, Yunmei S, Zhipeng C, Qineng P. The preparation of silybin–phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm. 2006;307(1):77–82.

    Article  PubMed  Google Scholar 

  40. Lasonder E, Weringa WD. An NMR and DSC study of the interaction of phospholipid vesicles with some anti-inflammatory agents. J Colloid Interface Sci. 1990;139(2):469–78.

    Article  CAS  Google Scholar 

  41. Perrut M, Jung J, Leboeuf F. Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes: Part I: Micronization of neat particles. Int J Pharm. 2005;288(1):3–10.

    Article  CAS  PubMed  Google Scholar 

  42. Kumari R, Agrawal A, Ilango K, Singh G, Dubey G. In vivo evaluation of the antidepressant activity of a novel polyherbal formulation. Autism-Open Access. 2016;6(194):2.

    Google Scholar 

  43. Kavitha K. Evaluation of total phenols, total flavonoids, antioxidant, and anticancer activity of Mucuna pruriens seed extract. Asian J Pharm Clin Res. 2018;11(3):242–6.

    Article  Google Scholar 

  44. Jabbari M, Gharib F. Solvent dependence on antioxidant activity of some water-insoluble flavonoids and their cerium (IV) complexes. J Mol Liq. 2012;168:36–41.

    Article  CAS  Google Scholar 

  45. Nagajyothi P, Sreekanth T, Lee J-i, Lee KD. Mycosynthesis: antibacterial, antioxidant and antiproliferative activities of silver nanoparticles synthesized from Inonotus obliquus (Chaga mushroom) extract. J Photochem Photobiol B. 2014;130:299–304.

  46. Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017;108:36–49.

    Article  CAS  PubMed  Google Scholar 

  47. LeFevre M, Olivo R, Vanderhoff J, Joel D. Accumulation of latex in Peyer’s patches and its subsequent appearance in villi and mesenteric lymph nodes. Proc Soc Exp Biol Med. 1978;159(2):298–302.

    Article  CAS  PubMed  Google Scholar 

  48. Savić R, Luo L, Eisenberg A, Maysinger D. Micellar nanocontainers distribute to defined cytoplasmic organelles. Science. 2003;300(5619):615–8.

    Article  PubMed  Google Scholar 

  49. Hou Z, Li Y, Huang Y, Zhou C, Lin J, Wang Y, et al. Phytosomes loaded with mitomycin C–soybean phosphatidylcholine complex developed for drug delivery. Mol Pharm. 2013;10(1):90–101.

    Article  CAS  PubMed  Google Scholar 

  50. Yu F, Li Y, Chen Q, He Y, Wang H, Yang L, et al. Monodisperse microparticles loaded with the self-assembled berberine-phospholipid complex-based phytosomes for improving oral bioavailability and enhancing hypoglycemic efficiency. Eur J Pharm Biopharm. 2016;103:136–48.

    Article  CAS  PubMed  Google Scholar 

  51. Venema FR, Weringa WD. The interactions of phospholipid vesicles with some anti-inflammatory agents. J Colloid Interface Sci. 1988;125(2):484–92.

    Article  CAS  Google Scholar 

  52. Cai X, Luan Y, Jiang Y, Song A, Shao W, Li Z, et al. Huperzine A–phospholipid complex-loaded biodegradable thermosensitive polymer gel for controlled drug release. Int J Pharm. 2012;433(1–2):102–11.

    Article  CAS  PubMed  Google Scholar 

  53. Jena SK, Singh C, Dora CP, Suresh S. Development of tamoxifen-phospholipid complex: novel approach for improving solubility and bioavailability. Int J Pharm. 2014;473(1–2):1–9.

    Article  CAS  PubMed  Google Scholar 

  54. Jayanthi P, Lalitha P. Determination of the in vitro reducing power of the aqueous extract of Eichhornia crassipes (Mart.) Solms. J Pharm Res. 2011;4:4003–5.

  55. Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67(3):217–23.

    CAS  PubMed  Google Scholar 

  56. Willner P. The validity of animal models of depression. Psychopharmacology. 1984;83(1):1–16.

    Article  CAS  PubMed  Google Scholar 

  57. Thierry B, Steru L, Simon P, Porsolt R. The tail suspension test: ethical considerations. Psychopharmacology. 1986;90(2):284–5.

    Article  CAS  PubMed  Google Scholar 

  58. Gershon AA, Vishne T, Grunhaus L. Dopamine D2-like receptors and the antidepressant response. Biol Psychiat. 2007;61(2):145–53.

    Article  CAS  PubMed  Google Scholar 

  59. Monleon S, Parra A, Simon V, Brain P, D’Aquila P, Willner P. Attenuation of sucrose consumption in mice by chronic mild stress and its restoration by imipramine. Psychopharmacology. 1995;117(4):453–7.

    Article  CAS  PubMed  Google Scholar 

  60. Yalcin I, Aksu F, Belzung C. Effects of desipramine and tramadol in a chronic mild stress model in mice are altered by yohimbine but not by pindolol. Eur J Pharmacol. 2005;514(2–3):165–74.

    Article  CAS  PubMed  Google Scholar 

  61. Dhir A, Kulkarni S. Involvement of dopamine (DA)/serotonin (5-HT)/sigma (σ) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist. Brain Res Bull. 2007;74(1–3):58–65.

    Article  CAS  PubMed  Google Scholar 

  62. Lu M, Qiu Q, Luo X, Liu X, Sun J, Wang C, et al. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian J Pharm Sci. 2019;14(3):265–74.

  63. Awasthi R, Kulkarni G, Pawar VK. Phytosomes: an approach to increase the bioavailability of plant extracts. Int J Pharm Pharm Sci. 2011;3(2):1–3.

    Google Scholar 

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Acknowledgements

The authors are thankful to Alkem Laboratories Pvt. Ltd., Mumbai, India, for providing the drug levodopa. The authors are also thankful to Amsar Goa Pvt. Ltd, Goa, India, for providing Mucuna prureins extract and VAV Pvt. Ltd, Mumbai, India, for providing Soya Phosphatidylcholine (SPC; LECIVA S-70) as gift samples. The authors also extend thanks to Shivaji University, Kolhapur, and Savitribhai Phule University, Pune, India, to perform characterization studies. The authors also extend gratitude to Crystal Biology Solutions, Pune, India, for performing in vivo antidepressant activity. The laboratory facilities provided by Principal, Bharati Vidyapeeth College of Pharmacy, Kolhapur, India, and Principal, Indira College of Pharmacy, Pune, India, are also acknowledged gratefully.

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This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Karekar, P., Killedar, S., Kulkarni, S. et al. Design and Optimization of Nanophytosomes Containing Mucuna prureins Hydroalcoholic Extract for Enhancement of Antidepressant Activity. J Pharm Innov 18, 310–324 (2023). https://doi.org/10.1007/s12247-022-09646-w

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