AN UPDATE ON BIO-POTENTIATION OF DRUGS USING NATURAL OPTIONS
The objective of this review is to put a light on the benefits of bio-enhancers and their role in developing a proper drug delivery system having improved therapeutic action and least drawbacks. As medical science is developing fast and there is a considerable increase in the development of new drugs with many therapeutic activities, but having lots of side effects, less in vivo action, or are very costly. These drawbacks create an enormous demand for use of bio-enhancers to reduce the dose required of the active ingredients and provide a suitable condition for their actions. There are vast nature-derived bio-enhancers originated from plants or other natural sources, used to a great extent as they show high activity and have very little or no adverse effects. Bio-enhancers increase bioavailability in various ways such as by increasing drug absorption, decreasing drug metabolism, and by other methods, which helps the drug having low bioavailability but the good therapeutic potential to show its effect fast. The concept of bio-enhancers developing increasingly in modern medicine but in reality, was there and well explained in Ayurveda texts with various herbal drugs such as piperine, quercetin, genistein, naringin and some non-herbal compounds such as cow urine distillate, and Capmul. Along with these nature-derived bio-enhancers and the new techniques such as liposomes, nanoparticles, transferosomes, and ethosomes resulted in the successful modification of suitable dosage forms. The concept of bioenhancers and their application is a great tool which can lead to a excellent development of medical science.
2. Atal CK. A breakthrough in drug bioavailability a clue from age old wisdom of Ayurveda. IDMA Bull 1979;10:483-4.
3. Johri RK, Zutshi U. An ayurvedic formulation “trikatu” and its constituents. J Ethnopharmacol 1992;37:85-91.
4. Lundin S, Artursson P. Absorption enhancers as an effective method in improving the intestinal absorption. Int J Pharm 1990;64:181-6.
5. Aungst BJ, Blake JA, Hussain MA. An in vitro evaluation of metabolism and poor membrane permeation impeding intestinal absorption of leucine enkephalin and methods to increase absorption. J Pharmacol Exp Ther 1991;259:139-45.
6. Schipper NG, Olsson S, Hoogstraate JA, Boer AG, Varum KM, Artursson P. Chitosan an absorption enhancers for poorly absorbable drugs: Influence of molecular weight and degree of acetylation on drug transport across human intestinal epithelial(caco-2) cells. Pharm Res 1996;113:1686-92.
7. Liversidge GG, Cundy KC. Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs. Int J Pharm 1995;125:91-7.
8. Veiga F, Fernandes C, Teixeira F. Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin inclusion complexes. Int J Pharm 2000;202:165-71.
9. Varma MV, Ashokraj Y, Dey CS, Panchagnula R. P-glycoprotein inhibitors and their screening: A perspective from bioavailability enhancement. Pharmacol Res 2003;48:347-59.
10. Annamalai AR, Manavalan R. Effects of trikatu and its individual components and piperine on gastrointerstinal tracts: Trikatua bioavailable enhancer. Indian Drugs 1989;27:595-604.
11. Bajad S, Bedi KL, Singla AK, Johri RK. Piperine inhibits gastric emptying and gastrointestinal transit in rats and mice. Planta Med 2001;67:176-9.
12. Majeed M, Badmaev V, Rajendran R. Use of Piperine to Increase the Bioavailability of Nutritional Compounds. United States: United States Patent, Number US5536506A; 1995.
13. Khajuria A, Thusu N, Zutshi U. Piperine modulates permeability characteristics of intestine by inducing alterations in membrane dynamics: Influence on brush border membrane fluidity, ultrastructure and enzyme kinetics. Phytomedicine 2002;9:224-31.
14. Reanmongkol W, Janthasoot W, Wattanatorn W, Upakorn PD, Chudapongse P. Effects of piperine on bioenergetics functions of isolated rat liver mitochondria. Biochem Pharmacol 1988;37:753-7.
15. Atal CK, Dubey RK, Singh J. Biochemical basis of enhanced drug bioavailability by piperine: Evidence that piperine is a potent inhibitor of drug metabolism. J Pharmacol Exp Ther 1985;232:258-62.
16. Johri RK, Thusu N, Khajuria A, Zutshi U. Piperine mediated changes in the permeability of rat intestinal epithelial cells: Status of gamma glutamyl transpeptidase activity, uptake of amino acids and lipid peroxidation. Biochem Pharmacol 1992;43:1401-7.
17. Cho SW, Lee JS, Choi SH. Enhanced oral bioavailability of poorly absorbed drugs. I. Screening of absorption carrier for the ceftriaxone complex. J Pharm Sci 2004;93:612-20.
18. Randhawa GK. Cow urine distillate as bioenhancer. J Ayurveda Integr Med 2010;1:240-1.
19. Chivte VK, Tiwari SV, Pratima A, Nikalge G. Bioenhancers: A brief review. Adv J Pharm Life Sci Res 2017;2:1-18.
20. Nijveldt RJ, Nood EV, van Hoorn DE, Boelens PG, Norren K, van Leeuwen PA. Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001;74:418-25.
21. Hoi JS, Li X. Enhanced diltiazem bioavailability after oral administration of diltiazem with quercetin to rabbits. Int J Pharm 2005;297:1-8.
22. Dupuy J, Larrieu G, Sutra JF, Lespine A, Alvinerie M. Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: Quercetin. Vet Parasitol 2003;112:337-47.
23. Miniscalco A, Landahl J, Regardh CG, Edgar B, Eriksson UG. Inhibition of dihydropyridine in rat and human liver microsomes by flavonoids found in grapefruit juice. J Pharmacol Exp Ther 1992;261:1195-9.
24. Scambia G, Ranelletti FO, Panici PB, De Vincenzo R, Bonanno G, Ferrandina G, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast-cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 1994;34:459-64.
25. Anup K, Sonia G, Swati K, Shrirang N, Waheed R, Vadim I, et al. The Studies on Bioenhancer Effect of Red Onions and Other Nutrients on the Absorption of Epigallocatechin Gallate from Green Tea Extract in Human Volunteers. Boston: 2nd International Conference on Tumor Progression and Therapeutic Resistance Proceedings; 2005. p. 89.
26. Palle S, Neerati P. Enhancement of oral bioavailability of rivastigmine with quercetin nanoparticles by inhibiting CYP3A4 and esterases. Pharmacol Rep 2017;69:365-70.
27. Kurzer M, Xu X. Dietary phytoestrogens. Annu Rev Nutr 2003;17:353-81.
28. Sparreboom A, van Asperen J, Mayer U, Schinkel AH, Smit JW, Meijer DK, et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc Natl Acad Sci USA 1997;94:2031-5.
29. Doyle LA, Ross DD. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 2003;22:7340-58.
30. Huisman MT, Chhatta AA, Tellingen OV, Beijnen JH, Schinkel AH. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Int J Cancer 2005;116:824-9.
31. Zhang H, Wong CW, Coville PF, Wanwimolruk S. Effect of the grapefruit flavonoid naringin on pharmacokinetics of quinine in rats. Drug Metabol Drug Interact 2000;17:351-63.
32. Lim SC, Choi JS. Effects of naringin on the pharmacokinetics of intravenous paclitaxel in rats. Biopharm Drug Dispos 2006;27:443-7.
33. Cheng SS, Fu SX, Li YS, Wang NC. The pharmacology of sinomenine I: The analgesic and anti-phlogistic actions and acute toxicity. Acta Pharmacol Sin 1964;4:177-80.
34. Takeda S, Isono T, Wakui Y, Matsuzaki Y, Sasaki H, Amagaya S, et al. Absorption and excretion of paeoniflorin in rats. J Pharm Pharmacol 1995;47:1036-40.
35. Liu ZQ, Zhou H, Liu L, Jiang ZH, Wong YF, Xie Y, et al. Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious rats. J Ethnopharmacol 2005;13:61-7.
36. Imai T, Sakai M, Ohtake H, Azuma H, Otagiri M. Absorption enhancing effect of glycyrrhizin induced in the presence of capric acid. Int J Pharm 2005;27:11-21.
37. Sakai M, Imai T, Ohtake H, Azuma H, Otagiri M. Simultaneous use of sodium deoxycholate and dipotassium glycyrrhizinate enhances the cellular transport of poorly absorbed compounds across caco-2 cell monolayers. J Pharm Pharmacol 1999;51:27-33.
38. Khanuja SP, Arya JS, Tiruppadiripuliyur RS, Saikia D, Kaur H, Singh M. Nitrile Glycoside Useful as a Bioenhancer of Drugs and Nutrients, Process of Its Isolation From Moringa oleifera. United States: United States Patent 6; 2006.
39. Khanuja SP, Arya JS, Srivastava SK, Shasany AK, Kumar S, Ranganathan T, et al. Antibiotic Pharmaceutical Composition with Lysergol as Bio-enhancer and Method of Treatment. United States: United States Patent, Number 20070060604; 2006.
40. Ogita A, Fujita K, Taniguchi M, Tanaka T. Enhancement of the fungicidal activity of amphotericin B by allicin, an allyl-sulfur compound from garlic, against the yeast Saccharomyces cerevisiae as a model system. Planta Med 2006;72:1247-50.
41. Chavhan SA, Shinde SA, Gupta HN. Current trends on natural bioenhancers: A review. Int J Pharmacogn Chin Med 2018;2:000123.
42. Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50.
43. Balakrishnan V, Varma S, Chatterji D. Piperine augments transcription inhibitory activity of rifampicin by severalfold in Mycobacterium smegmatis. Curr Sci 2001;80:1302-5.
44. Kapil RS, Zutshi U, Bedi KL. Process of Preparation of Pharmaceutical Composition with Enhanced Activity for Treatment of Tuberculosis and Leprosy. United States: United States Patent Number, US005439891 A; 1995.
45. Khan IA, Mirza ZM, Kumar A, Verma V, Qazi GN. Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. Antimicrob Agents Chemother 2006;50:810-2.
46. Reen RK, Wiebel FJ, Singh J. Piperine inhibits aflatoxin B1-induced cytotoxicity and geno toxicity in V79 Chinese hamster cells genetically engineered to express rat cytochrome P4502B1. J Ethnopharmacol 1997;58:165-73.
47. Selvendiran K, Singh JP, Krishnan KB, Sakthisekaran D. Cytoprotective effect of piperine against benzo[a]pyrene induced lung cancer with reference to lipid peroxidation and antioxidant system in albino mice. Fitoterapia 2003;74:109-15.
48. Choi BM, Kim SM, Park TK, Li G, Hong SJ, Park R, et al. Piperine protects cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells. J Nutr Biochem 2007;18:615-22.
49. Badmaev V, Majeed M, Norkus EP. Piperine, an alkaloid derived from black pepper increases serum response of beta-carotene during 14-days of oral betacarotene supplementation. Nutr Res1999;19:381-8.
50. Zargari A. Medicinal Plants. Vol. 2. Tehran: Tehran University Press; 1989. p. 519-21.
51. Qazi GN, Bedi KL, Johri R, Tikoo MK, Tikoo AK, Sharma SC, et al. Bioavailability/Bioefficacy Enhancing Activity of Cuminum cyminum and Extracts and Fractions Thereof. United States: United States Patent 7514105; 2009.
52. Boumendjel A, Di Pietro A, Dumontet C, Barron D. Recent advances in the discovery of flavonoids and analogs with high-affinity binding to P-glycoprotein responsible for cancer cell multidrug resistance. Med Res Rev 2002;22:512-29.
53. Qazi GN, Tikoo GL, Gupta AK, Ganjoo SK, Gupta DK, Jaggi BS, et al. Bioavailability Enhancing Activity of Zingiber officinale and its Extracts/Fractions Thereof. European: European Patent Number EP 1465646; 2002.
54. Vinson JA, Kharrat HA, Andreoli L. Effect of Aloe vera preparations on the human bioavailability of vitamins C and E. Phytomedicine 2005;12:760-5.
55. Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: From ancient medicine to current clinical trials. Cell Mol Life Sci 2008;65:1631-52.
56. Available from: http://www.patentstorm.us/patents/6896907/ description.html. [Last accessed on 2010 Sep 02].
57. Ganaie JA, Shrivastava VK. Effects of gonadotropin releasing hormone conjugate immunization and bioenhancing role of kamdhenu ark on estrous cycle, serum estradiol and progesterone levels in female Mus musculus. Int J Reprod Biomed 2010;8:70-5.
58. Khan A, Srivastava V. Antitoxic and bioenhancing role of kamdhenu ark (cow urine distillate) on fertility rate of male mice (Mus musculus) affected by cadmium chloride toxicity. Int J Cow Sci 2005;1:43-6.
59. Wagner V, Dullaart A, Bock AK, Zweck A. The emerging nanomedicine landscape. Nat Biotechnol 2006;24:1211-7.
60. Singh S, Tripathi JS, Rai NP. An appraisal of the bioavailability enhancers in ayurveda in the light of recent pharmacological advances. Ayu 2016;37:3-10.
61. Raut SV, Nemade LS, Desai MT, Bonde SD, Dongare SU. Chemical penetration enhancers: For transdermal drug delivery systems. Int J Pharm Rev Res 2014;4:33-40.
62. Patil UK, Saraogi R. Natural products as potential drug permeation enhancer in transdermal drug delivery system. Arch Dermatol Res 2014;306:419-26.
63. Mirza ZM, Kumar A, Kalia NP, Zargar A, Khan IA. Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. J Med Microbiol 2011;60:1472-8.
64. Ajazuddin SS, Saraf S. Applications of novel drug delivery system for herbal formulations. Nanomed Nanotechnol Biol Med 2008;4:70-8.
65. Samaligy MS, Afifi NN, Mahmoud EA. Evaluation of hybrid liposomes-encapsulated silymarin regarding physical stability and in vivo performance. Int J Pharm 2006;319:121-9.
66. Xiao L, Zhang YH, Xu JC, Jin XH. Preparation of floating rutin-alginate-chitosan microcapsule. Chin Tradit Herb Drugs 2008;2:209-12.
67. You J, Cui F, Han X, Wang Y, Yang L, Yu YW, et al. Study of the preparation of sustained-release microspheres containing zedoary turmeric oil by the emulsion-solvent-diffusion method and evaluation of the self-emulsification and bioavailability of the oil. Colloids Surf B Biointerfaces 2006;48:35-41.
68. Mei Z, Chen H, Weng T, Yang Y, Yang X. Solid lipid nanoparticle and microemulsion for topical triptolide. Eur J Pharm Biopharm 2003;56:189-96.
69. Su YL, Fu ZY, Zhang JY, Wang WM, Wang H, Wang YC, et al. Microencapsulation of radix Salvia miltiorrhiza nanoparticles by spray-drying. Powder Technol 2008;184:114-21.
70. Xiao YL, Luo JB, Yan ZH, Rong HS, Huang WM. Preparation and in vitro and in vivo evaluations of topically applied capsaicin transferosomes. Yao Xeu Xeu Bao 2006;41:461-6.
71. Singh HP, Utreja P, Tiwary AK, Jain S. Elastic liposomal formulation for sustained delivery of colchicine: In vitro characterization and in vivo evaluation of anti-gout activity. AAPS J 2009;11:54-64.
72. Bhattacharya S, Ghosh A. Phytosomes: The emerging technology for enhancement of bioavailability of botanicals and nutraceuticals. Int J Health Res 2009;2:225-9.
73. Goyal A, Kumar S, Nagpal M, Singh I, Arora S. Potential of novel drug delivery systems for herbal drugs. Indian J Pharm Educ Res 2011;45:225-35.
74. Shankar SS, Rai A, Ahmad A, Sastry M. Rapid synthesis of Au, Ag and bimetallic Au core-Ag shell nanoparticles using neem (Azadirachta indica) leaf broth. J Colloid Interface Sci 2004;275:496-502.
75. Huang J, Li Q, Sun D, Lu Y, Su Y, Yang X, et al. Biosynthesis of silver and gold nanoparticles by novel sundried Cinnamomum canphora Leaf. Nanotechnology 2007;18:105104.
76. Chandra PS, Chaudhary M, Pasricha R, Ahmad A, Sastry M. Synthesis of gold nanotriangles and silver nanoparticles using Aloe vera plant extract. Biotechnol Prog 2006;22:577-83.
77. Kheradmandnia S, Farahani VE, Nosrati M, Atyabi F. Preparation and characterization of ketoprofen loaded solid lipid nanoparticles made from beeswax and carnauba wax. Nanomed Nanotechnol Biol Med 2010;6:753-9.
78. Tiyaboonchai W, Tungpradit W, Plianbangchang P. Formulation and characterization of curcuminoids loaded solid lipid nanoparticles. Int J Pharm 2007;337:299-306.
79. Wang S, Chen T, Ruie C, Hu Y, Chen M, Wang Y. Emodin loaded solid lipid nanoparticles: Preparation, characterization and anti tumour activity studies. Int J Pharm 2012;430:238-46.
80. Kuchler S, Wolf BN, Heilmann S, Weindl G, Helfmann J, Yahya MM, et al. 3D wound healing model: Influence of morphine and solid lipid nanoparticles. J Biotechnol 2010;148:24-30.
81. Yuan H, Miao J, Du ZY, You J, Hu QF, Zeng S. Cellular uptake of solid lipid nanoparticles and cytotoxicity of encapsulated paclitaxel in A549 cancer cells. Int J Pharm 2008;348:137-45.
82. Chen H, Chang X, Du D, Liu W, Liu J, Weng T, et al. Podophyllotoxin loaded solid lipid nanoparticles for epidermal targeting. J Control Release 2006;110:296-306.
83. Jenning V, Gysler A, Korting SM, Gehla HS. Vitamin A loaded solid lipid nanoparticles for topical use: Occlusive properties and drug targeting to the upper skin. Eur J Pharm Biopharm 2000;49:211-8.
84. Bano G, Amla V, Raina RK, Zutshi U, Chopra CL. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9.
85. Pahri P, Mohanty C, Sahoo SK. Nanotechnology based combinational drug delivery: An emerging approach for cancer drug therapy. Drug Discov Today 2012;17:1044-52.
86. Rajendran R, Radhai R, Kotresh TM, Csiszar E. Development of antimicrobial cotton fabrics using herb loaded nanoparticles. Carbohydr Polym 2013;91:613-7.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.