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Bioenhancers from mother nature: an overview
Future Journal of Pharmaceutical Sciences volume 9, Article number: 20 (2023)
Abstract
Background
The concept of bioenhancer comes from Ayurveda. Many ways have been documented in the literature to boost the bioavailability of poorly bioavailable medications, and one of the most recent techniques is the use of bioavailability enhancers.
Main body of the abstract
Herbal bioenhancers are a choice of bioenhancer in modern medicine because of their easy absorption, safety, and lack of side effects. They also reduce drug toxicity, decrease treatment times, and lower treatment costs. Increasing drug bioavailability after oral administration is medically relevant since bioavailability has a direct impact on plasma drug concentrations and therapeutic bioefficacy. When medicine is coupled with a suitable bioenhancer, the bioavailability of the drug is increased. The drug and bioenhancers have no synergistic effect. They reduce the dosage, cost, toxicity, and other side effects, as well as the amount of time it takes to act.
Short conclusion
The objective of these survey is that to investigate the thought of the bioavailability to get a superior therapeutic response within the right portion with natural pharmaceuticals containing product, as well as the classification of bioenhancers, mechanism of action, commercial formulation, and future prospects.
Background
Today, there is a medical need and interest in improving the bioavailability of poorly bioavailable, costly, and dangerous medications that are administered for lengthy periods of time. Poorly bioavailable medications continue to be sub-therapeutic since a significant portion of dosage does not ever achieve a plasma drug concentration as well as exerts its pharmacological activity until and unless exceptionally high dosages are given, which can produce substantial adverse effects. A multitude of variables can contribute to poor oral bioavailability, including poor dissolution and poor solubility in water, intestinal barrier permeability, drug degradation in gastrointestinal as well as intestinal fluid, including systemic intestinal as well as hepatic metabolism [1].
As a result, drug compounds that do not have the same therapeutic action but improve bioavailability when coupled with other medications or molecules are needed. When taken with another medicine, several natural substances of plant origin can improve bioavailability. As a result, bioenhancers are chemical compounds that boost the bioavailability of low bioavailable medications when combined with bioenhancers, but do not have a synergistic impact with the drug [2].
Main text
Rational of bioavailability enhancement
"Biopotentiation or bioenhancement refers to the phenomena of enhancing the overall occurrence of any chemical substance in the biological fluid and systemic circulation, as well as secondary chemicals responsible for the increase in plasma drug concentration of the major component” [3].
Bioenhancers are utilised in a variety of methods to promote bioavailability. Absorption boosters, prodrugs, permeability boosters, micronisation, and formulations of prolonged and sustained release pharmaceutical formulations such as liposomes and emulsions, as well as P-glycoprotein inhibitors are all examples of specific strategies (P-GP) [4].
Bioenhancers with ideal properties [5, 6]
Bioenhancers have the following properties
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It should be nontoxic in nature.
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It should be simple to formulate.
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At a very low concentration, it should show its effect when combined with the drug.
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It should increase the absorption and activity of the drug.
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Compliance is simple.
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Because of the low cost, acceptance is simple.
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Easily accessible.
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It must be non-irritating and allergy-free.
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It should be stable in its surroundings and quick to react.
Advantages of bioenhancer
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When a bioenhancer is used in combination with a drug, the drug’s dosage is decreased, and the possibility of drug resistance is minimised.
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Adverse drug responses or side effects, as well as drug toxicity, will be decreased as a result of the lower dose.
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This is particularly true with anticancer medications such as Taxol.
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Due to an improvement in bioavailability, the drug's efficacy has increased.
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As drug bioavailability is increased, they can lower both inter-individual and intra-individual variability [7].
Disadvantages of bioenhancer
Despite the success of bioenhancers in drug delivery, there are still some challenges for new bioenhancers in development, such as
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Increasing the features of drug formulations such as blood circulation, functional surface area, drug dissolution protection, passing biological barriers, with site-specific targeting.
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Researching and developing bioenhancer for large-scale manufacturing is a challenge. Laboratory or pilot technologies must always be scaled up for ultimate commercialisation. Scaling-up problems include low nanoparticle concentrations, aggregation, and the chemical process; it is easier to modify nanoparticles in the laboratory.
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Regulations regulating the physiochemical and pharmacokinetic features of newer bioenhancers are required [8].
What exactly are bioenhancers?
“Bioavailability is the rate and amount to which an active pharmacological ingredient enters into systemic circulation and then becomes accessible at the necessary site of action.” When compared to oral delivery, intravenous medicines have the highest bioavailability since oral administration delivers a lower percentage due to partial drug absorption [9].
Definition
Bioenhancers are compounds that, when combined with pharmacological substances, stimulate and enhance drug bioavailability without having a synergistic activity with the drug.
Bioavailability enhancers are chemicals that, on their own, do not have the same effect as a traditional medicament. But when combined, they enhance drug macromolecular activity in a number of ways, including boosting drug bioavailability all across membranes, enhancing the drug molecule using conformational interactions, serving as drugs molecule receptors, and enhancing drug sensitivity in target cells. “A ‘bioenhancer’ is a chemical that increases the bioavailability and effectiveness of a medication it is combined with without having its own pharmacological action at the dose used” [10].
There are various benefits of using natural bioenhancer and are given in Fig. 1 [7]
History of bioenhancer
The term “bioavailability enhancer” was created by C.K. Atal, the Chairman of the Regional Research Laboratory at Jammu, when Piperine was discovered and scientifically demonstrated to be the first bioavailability booster in the history of the world in 1979. Bioenhancers are substances that, when taken orally, do not have any pharmacological effects on their own but rather increase biological activity or the uptake of the active ingredient and increase bioavailability during combination therapy [11].
The word “bioavailability enhancer” is derived from Trikatu, an Ayurvedic combination containing black pepper, long pepper, and ginger, is where the name “bioavailability enhancer” originates. Sanskrit word trikatu translates to “three acrids.” In 1929, Bose discovered the bioavailability enhancer activity. Trikatu is a Sanskrit word that means “three acrids.” Bose initially found the bioavailability enhancer action in 1929, when he detailed the effect of long pepper on Adhatodavasaka leaves, which improved Vasaka activity [12, 13].
Bioenhancers is an ancient Ayurvedic term that refers to the drug’s increasing effect, as well as the Sanskrit term “Yogvahi,” which means “to rise in effect” [14].
Classification of bioenhancers
Based on their properties, bioenhancers are divided into two groups. Bioenhancers can be classified into the following types:
Bioenhancers based on origin
Based on their origin, bioenhancers are classified into the following classes [15, 16]
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I.
Bioenhancers derived from plant sources These bioenhancers are made up of different plant parts. Secondary metabolites from a variety of medicinal and aromatic plants are thought to be a rich source of bioenhancers (Table 1).
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II.
Bioenhancers derived from other than plant sources Bioenhancers originating from non-herbal sources are number two. Non-herbal and synthetic chemical compounds can be used to obtain and synthesis these bioenhancers.
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III.
Bioenhancers from plant sources
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IV.
Bioenhancer from other than plant sources
Capmul
Source Glycerolysis of specified fats and oils, as well as esterification of glycerin with specific fatty acids, is used to make capmul (mono-, di-, and triglyceride).
Mechanism of action Capmul functions as a very effective transporter and solubiliser of active chemicals due to its lipophilic nature. Due to its mono-diglyceride medium-chain esters, which are used to dissolve troublesome compounds like sterols, it also has bacteriostatic properties. [27]
Drugs Ceftriaxone 70 (Capmul’s lipophilic nature contributes in improving Ceftriaxone 70's solubility.)
Distillate of cow urine
Cow urine distillate is more effective as a bioenhancer as compared to cow urine. Its Rasayana helps to modulate the immune system and acts as a bioenhancer [28].
Bioenhancers based on mechanism of action [10]
Inhibitors of P-gp efflux pumps | Example: Cuminumcyminum (Black cumin), Carumcarvi (caraway), Genistein, Sinomenine, Naringin, Quercetin |
Suppressors of CYP-450 enzyme and its isozymes | Example: Naringin, gallic acid, and its ester, quercetin |
Regulators of GIT function to facilitate better absorption | Example: Niaziridin (drumstick pods), Zingiber Officinale (ginger), Aloe vera (Aloe), and glycyrrhizin (licorice) |
Mechanism of action of bioenhancers
Herbal bioenhancers work through a variety of processes. Different bioenhancers may have the same or different mechanisms of action. Nutritional bioenhancers work on the gastrointestinal tract to improve absorption. Antimicrobial bioenhancers primarily influence drug metabolism. [6, 29]
The following are the main mechanisms by which different bioenhancers increase the bioavailability of the medicinal component [30]:
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By enhancing the GIT tract’s blood supply, orally administered drugs are better absorbed.
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Active transporters at diverse places, like glycoprotein (p-GP), the efflux pumps that pumps drugs out of the body and prevents them from reaching its target site, can be modified. Bioenhancer works in these situations by blocking the pop-up from opening.
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Inhibiting drug metabolism enzymes such as CYP3A4, CYP1A1, CYP1B2, and CYP2E1 in the liver, stomach, lungs, and other sites. This will also help with the first-pass action of drugs.
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Reducing passive tubular reabsorption and preventing glomerular filtration as well as active tubular secretion by inhibiting renal clearance. Inhibiting the UDP glucuronosyl transferase enzyme, that conjugates and inactivates the drug, may occasionally obstruct biliary passage.
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Some of the other mechanisms of action of bioenhancers are shown in Figs. 2 and 3.
Marketed formulation
Significant information has been published in a number of national and international journals by the Regional Research Laboratory, Jammu (RRL), and patent applications were filed in India, USA, as well as the Europe. Ant tubercular formulations were created following the proposed step-by-step medication development methodology. The Drug Control General of India (DCGI) granted a licence for antitubercular formulations to be commercialised in India following the conclusion of Phase IIIb clinical studies.
November of 2009, the Medication Control General of India (DCGI) approved CandilaPharma’s commercial version of antitubercular drug Risorine, It contains 10 mg of piperine, 300 mg of isoniazid, and 200 mg of rifampicin. When Rifamicin was combined with Piperine, its bioavailability increased by 60%. As a result, Piperine reduced the rifampicin dose from 450 to 200 mg, lowering the drug’s cost, dosage, and toxicity [31].
Some of the recent formulations of natural bioenhancers are given in below table (Table 2—Liposomal formulation, Table 3—Nanoparticle Formulation, Table 4—Transferosome Formulation, Table 5—Microspheres Formulation).
Future prospectus
In today's world, the concept of bioenhancers has proven to be quite revolutionary. The dose of bioenhancers is lowered, and the risk of drug resistance is reduced. Due to the lower dosage, the toxicity of the drugs is lower; this is especially true for cancer drugs such as Taxol.
There are also environmental benefits. The bark of the Pacific yew, one of the largest and slowest growing plants in the world, is used to produce Taxol, a drug used to treat prostate and ovarian cancer. Currently, six trees between 25 and 100 years old would have to be cut down to cure one patient. As a result of bioenhancers, fewer people will die.
Conclusion
The cost of therapy in poor countries like India is a major challenge for modern medicine. Systematic and imaginative techniques are needed to reduce these costs. Researchers are currently investigating strategies to reduce drug doses, and thus treatment costs, so that therapy becomes relatively accessible to a wide range of patients, including the poor.
Enhancement technology is based on the existing medical system, but it is a rapidly evolving sector. New methods of drug discovery are advancing rapidly, but the economics of drug development are a concern. Researchers are currently working on a way to reduce drug doses, and thus the cost of treatment, and make therapy accessible to broad populations, including financial support for the country. The bioenhancing phenomenon is useful in a variety of situations and provides relief to society because of its side effects.
Availability of data and materials
The data that support the findings of this study are available from the corresponding author, upon reasonable request.
Abbreviations
- GIT:
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Gastrointestinal tract
- AUC:
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Area under the curve
- Cmax:
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Peak concentration
- UDP:
-
Uranyl di-phosphate
- P-GP:
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P-glycoprotein
- RRL:
-
Regional Research Laboratory
- DCGI:
-
Drug Control General of India
References
Javed S, Ahsan W, Kohli K (2016) The concept of bioenhancers in bioavailability enhancement of drugs: a patent review. J Sci Lett 1:143–165
Tatiraju DV, Bagade VB, Karambelkar PJ, Jadhav VM, Kadam V (2013) Natural bioenhancers: an overview. J Pharmacogn Phytochem 2(3):55–60
Jhanwar B, Gupta S (2014) Biopotentiation using herbs: novel technique for poor bioavailable drugs. Int J Pharm Tech Res 6(2):443–454
Muttepawar SS, Jadhav SB, Kankudate AD, Sanghai SD, Usturge DR, Chavare SS (2014) A review on bioavailability enhancers of herbal origin. World J Pharm Pharm Sci (WJPPS) 3(3):667–677
Kumar M, Kumar D, Kumar S, Kumar A, Mandal UK (2022) A Recent Review on Bio-availability Enhancement of Poorly Water-soluble Drugs by using Bioenhancer and Nanoparticulate Drug Delivery System. Curr Pharm Des 28(39):3212–3224
Iswariya T, Pradesh A, Gupta S (2019) Bioavailability enhancers: an overview. IJARIIT 5:825–829
Alexander A, Qureshi A, Kumari L, Vaishnav P, Sharma M, Saraf S, Saraf S (2014) Role of herbal bioactives as a potential bioavailability enhancer for active pharmaceutical ingredients. Fitoterapia 97:1–14
Prasad R, Singh A, Gupta N, Tarke C (2016) Role of bioenhancers in tuberculosis. Int J Health Sci Res 6(6):307–313
Randhawa GK, Kullar JS (2011) Bioenhancers from Mother nature and their applicability in modern medicine. Int J Appl Basic Med Res 1(1):5
Kesarwani K, Gupta R (2013) Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed 3(4):253–266
Vijayarani KR, Govindarajulu M, Ramesh S, Alturki M, Majrashi M, Fujihashi A, Almaghrabi M, Kirubakaran N, Ren J, Babu RJ, Smith F (2020) Enhanced bioavailability of boswellic acid by Piper longum: a computational and pharmacokinetic study. Front Pharmacol 11:551911. https://doi.org/10.3389/fphar.2020.551911
Shukla M, Malik MY, Jaiswal S, Sharma A, Tanpula DK, Goyani R, Lal J (2016) A mechanistic investigation of the bioavailability enhancing potential of lysergol, a novel bioenhancer, using curcumin. RSC Adv 6(64):58933–58942
Chavhan SA, Shinde SA, Gupta INN (2018) Current trends on natural bio enhancers: a review. Intern J Pharmacogn Chin Med 2:2576–4772
Zafar N, Pharm M (2017) Herbal bioenhancers: a revolutionary concept in modern medicine. Zafar World J Pharm Res [Internet] 6(16):381–397
Jain G, Patil UK (2015) Strategies for enhancement of bioavailability of medicinal agents with natural products. Int J Pharm Sci Res 6(12):5315–5324
Singh A, Verma BK, Pandey S (2021) Exploring natural bioenhancers to enhancing bioavailability: an overview. Int J Pharm Life Sci 12(2):24–31
Mirza ZM, Kumar A, Kalia NP, Zargar A, Khan IA (2011) Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. J Med Microbiol 60(10):1472–1478
Moorthi C, Kathiresan K (2013) Curcumin–Piperine/Curcumin–Quercetin/Curcumin–Silibinin dual drug-loaded nanoparticulate combination therapy: a novel approach to target and treat multidrug-resistant cancers. J Med Hypotheses Ideas 7(1):15–20
Kulkarni SK, Bhutani MK, Bishnoi M (2008) Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 201(3):435–442
Sanmukhani J, Anovadiya A, Tripathi CB (2011) Evaluation of antidepressant like activity of curcumin and its combination with fluoxetine and imipramine: an acute and chronic study. Acta Pol Pharm 68(5):769–775
Dabeek WM, Marra MV (2019) Dietary Quercetin and Kaempferol: bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients 11(10):2288. https://doi.org/10.3390/nu11102288
Ghayur MN, Gilani AH (2005) Pharmacological basis for the medicinal use of ginger in gastrointestinal disorders. Dig Dis Sci 50(10):1889–1897
Sahu PK, Giri DD, Singh R, Pandey P, Gupta S, Shrivastava AK, Kumar A, Pandey KD (2013) Therapeutic and medicinal uses of Aloe vera: a review. Pharmacol Pharm 4(08):599
Johri RK (2011) Cuminum cyminum and Carum carvi: an update. Pharmacogn Rev 5(9):63
Amin S, Mir SR, Kohli K, Ali B, Ali M (2010) A study of the chemical composition of black cumin oil and its effect on penetration enhancement from transdermal formulations. Nat Prod Res 24(12):1151–1157
Sumano-López H, Gutiérrez-Olvera L, Aguilera-Jiménez R, Gutiérrez-Olvera C, Jiménez-Gómez F (2007) Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations. Arzneimittelforschung 57(05):286–290
Majumdar SH, Kulkarni AS, Kumbhar SM (2018) “Yogvahi (Bioenhancer)”: an ayurvedic concept used in modern medicines. Int Res J Pharm Med Sci 1(1):20–25
Pathak N (2020) Role of bioenhancers in drug discovery. Int J Pharm Life Sci 11(7):51
Maitra J (2018) A study on synergism between curcumin and aspirin. J Pharmacogn Phytochem 7(1):663–665
Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, Kamani DR, Chauhan BN (2012) A comprehensive review on pharmacotherapeutics of herbal bioenhancers. Sci World J. https://doi.org/10.1100/2012/637953
Atal N, Bedi KL (2010) Bioenhancers: revolutionary concept to market. J Ayurveda Integr Med 1(2):96
Gang W, Jie WJ, Ping ZL, Ming DS, Ying LJ, Lei W, Fang Y (2012) Liposomal quercetin: evaluating drug delivery in vitro and biodistribution in vivo. Expert Opin Drug Deliv 9(6):599–613
Wei Y, Lee RJ (2017) Liposomal curcumin and its application in cancer physical property. Int J Nanomed 12:6027–6044
Chiara S, Alessandro DL, Francesco L, Donatella V, Maria M, Giuseppe L (2005) Preparation and characterization of Artemisia arborescens liposomes. Eur J Pharm Biopharm 59:161–168
Pinilla CMB, Thys RCS, Brandelli A (2019) Antifungal properties of phosphatidylcholine-oleic acid liposomes encapsulating garlic against environmental fungal in wheat bread. Int J Food Microbiol 293:72–78
Vickers NJ (2017) Animal communication: when i’m calling you, will you answer too? Curr Biol 27(14):R713–R715
Chen Y, Lin X, Park H, Greever R (2009) Study of artemisinin nanocapsules as anticancer drug delivery systems. Nanomed: Nanotechnol Biol Med 5(3):316–322
Rathee P, Kamboj A, Sidhu S (2017) Enhanced oral bioavailability of nisoldipine-piperine-loaded poly-lactic-co-glycolic acid nanoparticles. Nanotechnol Rev 6(6):517–526
Kumar V, Chaudhary H, Kamboj A (2018) Development and evaluation of isradipine via rutin-loaded coated solid–lipid nanoparticles. Int Med Appl Sci 10(4):236–246
Ray L, Karthik R, Srivastava V, Singh SP, Pant AB, Goyal N, Gupta KC (2021) Efficient antileishmanial activity of amphotericin B and piperine entrapped in enteric coated guar gum nanoparticles. Drug Deliv Transl Res 11(1):118–130
Gade JV, Sharma PP, Jain B, Rawat R (2022) Synthesis and characterization of paclitaxel nanoparticles for drug delivery. Mater Today: Proc 51:445–450
Alharbi WS, Almughem FA, Almehmady AM, Jarallah SJ, Alsharif WK, Alzahrani NM, Alshehri AA (2021) Phytosomes as an emerging nanotechnology platform for the topical delivery of bioactive phytochemicals. Pharmaceutics 13(9):1475
Sarwa KK, Mazumder B, Rudrapal M, Verma VK (2015) Potential of capsaicin-loaded transfersomes in arthritic rats. Drug Deliv 22(5):638–646
Pingale PL, Ravindra RP (2013) Effect of Piper nigrum on in-vitro release of Isoniazid from oral microspheres. Int J Pharma Biosci 4(1):1027–1036
Khatri S, Awasthi R (2016) Piperine containing floating microspheres: an approach for drug targeting to the upper gastrointestinal tract. Drug Deliv Transl Res 6(3):299–307
Abourehab MA, Khaled KA, Sarhan HA, Ahmed OA (2015) Evaluation of combined famotidine with quercetin for the treatment of peptic ulcer: in vivo animal study. Drug Des Dev Ther 9:2159
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Thorat, S.S., Gujar, K.N. & Karale, C.K. Bioenhancers from mother nature: an overview. Futur J Pharm Sci 9, 20 (2023). https://doi.org/10.1186/s43094-023-00470-8
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DOI: https://doi.org/10.1186/s43094-023-00470-8