Abstract
Natural products have been widely explored since ancient times to heal human diseases. Due to their biological activities and relative safety, natural products have found applications in functional foods, medicine, pharmaceuticals and nutraceuticals. However, applications are often limited by poor aqueous solubility, instability and poor bioavailability following oral administration. For instance, many natural products exhibit excellent in vitro pharmacological activity, and no or less in vivo activity as a result of poor gastrointestinal absorption. Here we review techniques and materials for bioavailability enhancement such as particle size reduction, surfactant use, pH change, solid dispersion, cyclodextrin complexation, phytosome technology, solid-lipid nanoparticles, liposome and polymeric nanoparticles. Natural substances include quercetin, naringenin, curcumin, hesperetin, andrographolide, ellagic acid, resveratrol, bilobalide sinomenine, genistein, ginkgolide and glycyrrhizin. The clinical use of piperine as bio-enhancer with rifampicin is key achievement in the treatment of tuberculosis.
Similar content being viewed by others
References
Agueros M, Zabaleta V, Espuelas S, Campanero MA, Irache JM (2010) Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride) nanoparticles. J Control Release 145(1):2–8. https://doi.org/10.1016/j.jconrel.2010.03.012
Al-Kassas R, Bansal M, Shaw J (2017) Nanosizing techniques for improving bioavailability of drugs. J Control Release 260:202–212. https://doi.org/10.1016/j.jconrel.2017.06.003
Alam MA, Al-Jenoobi FI, Al-mohizea AM (2013) Commercially bioavailable proprietary technologies and their marketed products. Drug Discov Today 18(19–20):936–949. https://doi.org/10.1016/j.drudis.2013.05.007
Alam N, Dubey RD, Kumar A, Koul M, Sharma N, Sharma PR, Chandan BK, Singh SK, Singh G, Gupta PN (2015) Reduced toxicological manifestations of cisplatin following encapsulation in folate grafted albumin nanoparticles. Life Sci 142:76–85. https://doi.org/10.1016/j.lfs.2015.10.019
Allen TM, Cullis PR (2004) Drug delivery systems: entering the mainstream. Science 303(5665):1818–1822. https://doi.org/10.1126/science.1095833
Arora D, Saneja A, Jaglan S (2019) Cyclodextrin-based delivery systems for dietary pharmaceuticals. Environ Chem Lett 17(3):1263–1270. https://doi.org/10.1007/s10311-019-00878-w
Atal C, Zutshi U, Rao P (1981) Scientific evidence on the role of Ayurvedic herbals on bioavailability of drugs. J Ethnopharmacol 4(2):229–232. https://doi.org/10.1016/0378-8741(81)90037-4
Baek J-S, So J-W, Shin S-C, Cho C-W (2012) Solid lipid nanoparticles of paclitaxel strengthened by hydroxypropyl-β-cyclodextrin as an oral delivery system. Int J Mol Med 30(4):953–959. https://doi.org/10.3892/ijmm.2012.1086
Bagad M, Khan ZA (2015) Poly (n-butylcyanoacrylate) nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats. Int J Nanomed 10:3921. https://doi.org/10.2147/IJN.S80706
Bano G, Amla V, Raina R, Zutshi U, Chopra C (1987) The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 53(06):568–569. https://doi.org/10.1055/s-2006-962814
Bano G, Raina R, Zutshi U, Bedi K, Johri R, Sharma S (1991) Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 41(6):615–617. https://doi.org/10.1007/bf00314996
Bapat P, Ghadi R, Chaudhari D, Katiyar SS, Jain S (2019) Tocophersolan stabilized lipid nanocapsules with high drug loading to improve the permeability and oral bioavailability of curcumin. Int J Pharm 560:219–227. https://doi.org/10.1016/j.ijpharm.2019.02.013
Bhattaram VA, Graefe U, Kohlert C, Veit M, Derendorf H (2002) Pharmacokinetics and bioavailability of herbal medicinal products. Phytomedicine 9:1–33. https://doi.org/10.1078/1433-187x-00210
Brewster ME, Loftsson T (2007) Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev 59(7):645–666. https://doi.org/10.1016/j.addr.2007.05.012
Chen H, Wu J, Sun M, Guo C, Yu A, Cao F, Zhao L, Tan Q, Zhai G (2012) N-trimethyl chitosan chloride-coated liposomes for the oral delivery of curcumin. J Liposome Res 22(2):100–109. https://doi.org/10.3109/08982104.2011.621127
Cheng X, Zeng X, Zheng Y, Wang X, Tang R (2019) Surface-fluorinated and pH-sensitive carboxymethyl chitosan nanoparticles to overcome biological barriers for improved drug delivery in vivo. Carbohydr Polym 208:59–69. https://doi.org/10.1016/j.carbpol.2018.12.063
Crini G, Fourmentin S, Fenyvesi E, Torri G, Fourmentin M, Morin-Crini N (2018) Cyclodextrins, from molecules to applications. Environ Chem Lett 16(4):1361–1375. https://doi.org/10.1007/s10311-018-0763-2
Divya K, Jisha MS (2018) Chitosan nanoparticles preparation and applications. Environ Chem Lett 16(1):101–112. https://doi.org/10.1007/s10311-017-0670-y
Dubey RD, Alam N, Saneja A, Khare V, Kumar A, Vaidh S, Mahajan G, Sharma PR, Singh SK, Mondhe DM (2015) Development and evaluation of folate functionalized albumin nanoparticles for targeted delivery of gemcitabine. Int J Pharm 492(1–2):80–91. https://doi.org/10.1016/j.ijpharm.2015.07.012
Dubey RD, Saneja A, Gupta PK, Gupta PN (2016a) Recent advances in drug delivery strategies for improved therapeutic efficacy of gemcitabine. Eur J Pharm Sci 93:147–162. https://doi.org/10.1016/j.ejps.2016.08.021
Dubey RD, Saneja A, Qayum A, Singh A, Mahajan G, Chashoo G, Kumar A, Andotra SS, Singh SK, Singh G (2016b) PLGA nanoparticles augmented the anticancer potential of pentacyclic triterpenediol in vivo in mice. RSC Adv 6(78):74586–74597. https://doi.org/10.1039/C6RA14929D
Dutta PK, Sharma R, Kumari S, Dubey RD, Sarkar S, Paulraj J, Vijaykumar G, Pandey M, Sravanti L, Samarla M (2019) A safe and efficacious Pt (ii) anticancer prodrug: design, synthesis, in vitro efficacy, the role of carrier ligands and in vivo tumour growth inhibition. Chem Commun 55(12):1718–1721. https://doi.org/10.1039/C8CC06586A
El-Samaligy M, Afifi N, Mahmoud E (2006a) Increasing bioavailability of silymarin using a buccal liposomal delivery system: preparation and experimental design investigation. Int J Pharm 308(1–2):140–148. https://doi.org/10.1016/j.ijpharm.2005.11.006
El-Samaligy MS, Afifi NN, Mahmoud EA (2006b) Evaluation of hybrid liposomes-encapsulated silymarin regarding physical stability and in vivo performance. Int J Pharm 319(1–2):121–129. https://doi.org/10.1016/j.ijpharm.2006.04.023
Elsheikh MA, Elnaggar YS, Hamdy DA, Abdallah OY (2018) Novel cremochylomicrons for improved oral bioavailability of the antineoplastic phytomedicine berberine chloride: optimization and pharmacokinetics. Int J Pharm 535(1–2):316–324. https://doi.org/10.1016/j.ijpharm.2017.11.023
Farooq MA, Aquib M, Khan DH, Ghayas S, Ahsan A, Ijaz M, Banerjee P, Khan MA, Ahmad MM, Wang B (2019) Nanocarrier-mediated co-delivery systems for lung cancer therapy: recent developments and prospects. Environ Chem Lett 17(4):1565–1583. https://doi.org/10.1007/s10311-019-00897-7
Fu PP, Xia Q, Hwang H-M, Ray PC, Yu H (2014) Mechanisms of nanotoxicity: generation of reactive oxygen species. J Food Drug Anal 22(1):64–75. https://doi.org/10.1016/j.jfda.2014.01.005
Gabetta B, Bombardelli E, Pifferi G (1988) Complexes of flavanolignans with phospholipids, preparation thereof and associated pharmaceutical compositions. United States Patent US 4(764):508
Gera S, Talluri S, Rangaraj N, Sampathi S (2017) Formulation and evaluation of naringenin nanosuspensions for bioavailability enhancement. AAPS PharmSciTech 18(8):3151–3162. https://doi.org/10.1208/s12249-017-0790-5
Godugu C, Patel AR, Doddapaneni R, Somagoni J, Singh M (2014) Approaches to improve the oral bioavailability and effects of novel anticancer drugs berberine and betulinic acid. PLoS ONE 9(3):e89919. https://doi.org/10.1371/journal.pone.0089919
Gupta PN, Jain S, Nehate C, Alam N, Khare V, Dubey RD, Saneja A, Kour S, Singh SK (2014) Development and evaluation of paclitaxel loaded PLGA: poloxamer blend nanoparticles for cancer chemotherapy. Int J Biol Macromol 69:393–399. https://doi.org/10.1016/j.ijbiomac.2014.05.067
Gursoy RN, Benita S (2004) Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharm 58(3):173–182. https://doi.org/10.1016/j.biopha.2004.02.001
Hartono SB, Hadisoewignyo L, Yang Y, Meka AK, Yu C (2016) Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement. Nanotechnology 27(50):505605. https://doi.org/10.1088/09574484/27/50/505605
Hennenfent K, Govindan R (2005) Novel formulations of taxanes: a review. Old wine in a new bottle? Ann Oncol 17(5):735–749. https://doi.org/10.1093/annonc/mdj100
Hunter AC, Elsom J, Wibroe PP, Moghimi SM (2012) Polymeric particulate technologies for oral drug delivery and targeting: a pathophysiological perspective. Maturitas 73(1):5–18. https://doi.org/10.1016/j.maturitas.2012.05.014
Ingle SG, Pai RV, Monpara JD, Vavia PR (2018) Liposils: An effective strategy for stabilizing Paclitaxel loaded liposomes by surface coating with silica. Eur J Pharm Sci 122:51–63. https://doi.org/10.1016/j.ejps.2018.06.025
Johri R, Zutshi U (1992) An Ayurvedic formulation ‘Trikatu’and its constituents. J Ethnopharm 37(2):85–91. https://doi.org/10.1016/0378-8741(92)90067-2
Jounela A, Pentikäinen P, Sothmann A (1975) Effect of particle size on the bioavailability of digoxin. Eur J Clin Pharm 8(5):365–370. https://doi.org/10.1007/bf00562664
Kalepu S, Nekkanti V (2015) Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B 5(5):442–453. https://doi.org/10.1016/j.apsb.2015.07.003
Kawakami K, Oda N, Miyoshi K, Funaki T, Ida Y (2006) Solubilization behavior of a poorly soluble drug under combined use of surfactants and cosolvents. Eur J Pharm Sci 28(1–2):7–14. https://doi.org/10.1016/j.ejps.2005.11.012
Kesarwani K, Gupta R, Mukerjee A (2013) Bioavailability enhancers of herbal origin: an overview. Asian Pac J Trop Biomed 3(4):253–266. https://doi.org/10.1016/S2221-1691(13)60060-X
Khadka P, Ro J, Kim H, Kim I, Kim JT, Kim H, Cho JM, Yun G, Lee J (2014) Pharmaceutical particle technologies: an approach to improve drug solubility, dissolution and bioavailability. Asian J Pharm Sci 9(6):304–316. https://doi.org/10.1016/j.ajps.2014.05.005
Kidd P, Head K (2005) A review of the bioavailability and clinical efficacy of milk thistle phytosome: a silybin-phosphatidylcholine complex (Siliphos). Altern Med Rev 10(3):193–203. https://doi.org/10.1016/j.ajps.2014.05.005
Kidd PM (2009) Bioavailability and activity of phytosome complexes from botanical polyphenols: the silymarin, curcumin, green tea, and grape seed extracts. Altern Med Rev 14(3):226–46
Kumar P, Singh AK, Raj V, Rai A, Keshari AK, Kumar D, Maity B, Prakash A, Maiti S, Saha S (2018) Poly (lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid for improved treatment of hepatic cancer: characterization, in vitro and in vivo evaluations. Int J Nanomed 13:975. https://doi.org/10.2147/IJN.S157391
Kumar S, Randhawa JK (2013) High melting lipid based approach for drug delivery: solid lipid nanoparticles. Mater Sci Eng C 33(4):1842–1852. https://doi.org/10.1016/j.msec.2013.01.037
Leleux J, Williams RO (2014) Recent advancements in mechanical reduction methods: particulate systems. Drug Dev Ind Pharm 40(3):289–300. https://doi.org/10.3109/03639045.2013.828217
Lin C-H, Chen C-H, Lin Z-C, Fang J-Y (2017) Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal 25(2):219–234. https://doi.org/10.1016/j.jfda.2017.02.001
Liu C, Yang X, Wu W, Long Z, Xiao H, Luo F, Shen Y, Lin Q (2018) Elaboration of curcumin-loaded rice bran albumin nanoparticles formulation with increased in vitro bioactivity and in vivo bioavailability. Food Hydrocoll 77:834–842. https://doi.org/10.1016/j.foodhyd.2017.11.027
Lu Q, Dun J, Chen J-M, Liu S, Sun CC (2019) Improving solid-state properties of berberine chloride through forming a salt cocrystal with citric acid. Int J Pharm 554:14–20. https://doi.org/10.1016/j.ijpharm.2018.10.062
Md.AkhlaquerRanjitMohd.AamirSarfarajArshad RHMHH (2011) Oral lipid based drug delivery system (LBDDS): formulation, characterization and application: a review. Curr Drug Deliv 8(4):330–345. https://doi.org/10.2174/156720111795767906
Mukherjee PK, Harwansh RK, Bhattacharyya S (2015) Bioavailability of herbal products: approach toward improved pharmacokinetics evidence-based validation of herbal medicine. Elsevier, pp 217–245. https://doi.org/10.1016/B978-0-12-800874-4.00010-6
Munjal B, Pawar YB, Patel SB, Bansal AK (2011) Comparative oral bioavailability advantage from curcumin formulations. Drug Deliv Trans Res 1(4):322–331. https://doi.org/10.1007/s13346-011-0033-3
Nakagawa H, Miyata T, Mohri K, Sugimoto I, Manabe H (1978) Water of crystallization of berberine chloride (author's transl). Yakugaku Zasshi J Pharm Soc Jpn 98(8):981–985. https://doi.org/10.1248/yakushi1947.98.8_981
Nehate C, Jain S, Saneja A, Khare V, Alam N, Dhar Dubey R, Gupta NP (2014) Paclitaxel formulations: challenges and novel delivery options. Curr Drug Deliv 11(6):666–686. https://doi.org/10.2174/1567201811666140609154949
Oerlemans C, Bult W, Bos M, Storm G, Nijsen JFW, Hennink WE (2010) Polymeric micelles in anticancer therapy: targeting, imaging and triggered release. Pharm Res 27(12):2569–2589. https://doi.org/10.1007/s11095-010-0233-4
Pangeni R, Kang S-W, Oak M, Park EY, Park JW (2017) Oral delivery of quercetin in oil-in-water nanoemulsion: In vitro characterization and in vivo anti-obesity efficacy in mice. J Funct Foods 38:571–581. https://doi.org/10.1016/j.jff.2017.09.059
Parhi R (2020) Drug delivery applications of chitin and chitosan: a review. Environ Chem Lett 18(3):577–594. https://doi.org/10.1007/s10311-020-00963-5
Paroha S, Chandel AKS, Dubey RD (2018) Nanosystems for drug delivery of coenzyme Q10. Environ Chem Lett 16(1):71–77. https://doi.org/10.1007/s10311-017-0664-9
Paroha S, Dewangan RP, Sahoo PK (2020) Pharmaceutical technology for improving the bioavailability of natural products. In: Saneja APA, Lichtfouse E (eds) Sustainable agriculture reviews 43. Springer, pp 1–32. https://doi.org/10.1007/978-3-030-41838-0_1
Pisha E, Chai H, Lee I-S, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DM (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1(10):1046–1051. https://doi.org/10.1038/nm1095-1046
Rahman A, Hussain A, Iqbal Z, Kumar Harwansh R, Ratnakar Singh L, Ahmad S (2013) Nanosuspension: a potential nanoformulation for improved delivery of poorly bioavailable drug. Micro Nanosyst 5(4):273–287. https://doi.org/10.2174/187640290504131127121625
Rasenack N, Muller BW (2004) Micron-size drug particles: common and novel micronization techniques. Pharm Dev Technol 9(1):1–13. https://doi.org/10.1081/PDT-120027417
Saneja A, Kumar R, Mintoo MJ, Dubey RD, Sangwan PL, Mondhe DM, Panda AK, Gupta PN (2019) Gemcitabine and betulinic acid co-encapsulated PLGA− PEG polymer nanoparticles for improved efficacy of cancer chemotherapy. Mater Sci Eng C 98:764–771. https://doi.org/10.1016/j.msec.2019.01.026
Saneja A, Kumar R, Singh A, Dubey RD, Mintoo MJ, Singh G, Mondhe DM, Panda AK, Gupta PN (2017a) Development and evaluation of long-circulating nanoparticles loaded with betulinic acid for improved anti-tumor efficacy. Int J Pharm 531(1):153–166. https://doi.org/10.1016/j.ijpharm.2017.08.076
Saneja A, Sharma L, Dubey RD, Mintoo MJ, Singh A, Kumar A, Sangwan PL, Tasaduq SA, Singh G, Mondhe DM, Gupta PN (2017) Synthesis, characterization and augmented anticancer potential of PEG-betulinic acid conjugate. Mater Sci Eng C 73:616–626. https://doi.org/10.1016/j.msec.2016.12.109
Serajuddin AT (2007) Salt formation to improve drug solubility. Adv Drug Deliv Rev 59(7):603–616. https://doi.org/10.1016/j.addr.2007.05.010
Shanmugam S, Im HT, Sohn YT, Kim Y-I, Park J-H, Park E-S, Woo JS (2015) Enhanced oral bioavailability of paclitaxel by solid dispersion granulation. Drug Dev Ind Pharm 41(11):1864–1876. https://doi.org/10.3109/03639045.2015.1018275
Singh A, Worku ZA, Van den Mooter G (2011) Oral formulation strategies to improve solubility of poorly water-soluble drugs. Expert Opin Drug Deliv 8(10):1361–1378. https://doi.org/10.1517/17425247.2011.606808
Singh B, Bandopadhyay S, Kapil R, Singh R, Katare OP (2009) Self-emulsifying drug delivery systems (SEDDS): formulation development, characterization, and applications. Crit Rev Therap Drug Carrier Syst. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i5.10
Song Y, Gao H, Zhang S, Zhang Y, Jin X, Sun J (2017) Prescription optimization and oral bioavailability study of salvianolic acid extracts W/O/W multiple emulsion. Biol Pharm Bull 40(12):2081–2087. https://doi.org/10.1248/bpb.b17-00162
Song Y, Zhuang J, Guo J, Xiao Y, Ping Q (2008) Preparation and properties of a silybin-phospholipid complex. Pharmazie 63(1):35–42. https://doi.org/10.1691/ph.2008.7132
Sun M, Zhao L, Guo C, Cao F, Chen H, Zhao L, Tan Q, Zhu X, Zhu F, Ding T, Zhai Y, Zhai G (2012) Evaluation of an oral carrier system in rats: bioavailability and gastrointestinal absorption properties of curcumin encapsulated PBCA nanoparticles. J Nanoparticle Res 14(2):705. https://doi.org/10.1007/s11051-011-0705-4
Takahashi M, Uechi S, Takara K, Asikin Y, Wada K (2009) Evaluation of an oral carrier system in rats: bioavailability and antioxidant properties of liposome-encapsulated curcumin. J Agric Food Chem 57(19):9141–9146. https://doi.org/10.1021/jf9013923
Tran TH, Guo Y, Song D, Bruno RS, Lu X (2014) Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. J Pharm Sci 103(3):840–852. https://doi.org/10.1002/jps.23858
Uekama K, Fujinaga T, Otagiri M, Seo H, Tsuruoka M (1981) Enhanced bioavailability of digoxin by gamma-cyclodextrin complexation. J Pharm-Dyn 4(9):735–737. https://doi.org/10.1248/bpb1978.4.735
Vasconcelos T, Sarmento B, Costa P (2007) Solid dispersions as strategy to improve oral bioavailability of poor water soluble drugs. Drug Discov Today 12(23):1068–1075. https://doi.org/10.1016/j.drudis.2007.09.005
Wan S, Sun Y, Qi X, Tan F (2012) Improved bioavailability of poorly water-soluble drug curcumin in cellulose acetate solid dispersion. AAPS PharmSciTech 13(1):159–166. https://doi.org/10.1208/s12249-011-9732-9
Wang T, Wang N, Song H, Xi X, Wang J, Hao A, Li T (2011) Preparation of an anhydrous reverse micelle delivery system to enhance oral bioavailability and anti-diabetic efficacy of berberine. Eur J Pharm Sci 44(1):127–135. https://doi.org/10.1016/j.ejps.2011.06.015
Williams HD, Trevaskis NL, Charman SA, Shanker RM, Charman WN, Pouton CW, Porter CJ (2013) Strategies to address low drug solubility in discovery and development. Pharmacol Rev 65(1):315–499. https://doi.org/10.1124/pr.112.005660
Wong M-Y, Chiu GN (2011) Liposome formulation of co-encapsulated vincristine and quercetin enhanced antitumor activity in a trastuzumab-insensitive breast tumor xenograft model. Nanomed Nanotechnol Biol Med 7(6):834–840. https://doi.org/10.1016/j.nano.2011.02.001
Xu Y, Meng H (2016) Paclitaxel-loaded stealth liposomes: development, characterization, pharmacokinetics, and biodistribution. Artif Cells Nanomed Biotechnol 44(1):350–355. https://doi.org/10.3109/21691401.2014.951722
Yoshimatsu K, Nakabayashi S, Ogaki J, Kimura M, Horikoshi I (1981) Dielectric study on the water of crystallization of berberine chloride (author's transl). Yakugaku Zasshi J Pharm Soc Jpn 101(12):1143. https://doi.org/10.1248/yakushi1947.101.12_1143
Youssouf L, Bhaw-Luximon A, Diotel N, Catan A, Giraud P, Gimié F, Koshel D, Casale S, Bénard S, Meneyrol V, Lallemand L, Meilhac O, Lefebvre D’Hellencourt C, Jhurry D, Couprie J (2019) Enhanced effects of curcumin encapsulated in polycaprolactone-grafted oligocarrageenan nanomicelles, a novel nanoparticle drug delivery system. Carbohydr Polym 217:35–45. https://doi.org/10.1016/j.carbpol.2019.04.014
Yu F, Ao M, Zheng X, Li N, Xia J, Li Y, Li D, Hou Z, Qi Z, Chen XD (2017) PEG–lipid–PLGA hybrid nanoparticles loaded with berberine–phospholipid complex to facilitate the oral delivery efficiency. Drug Deliv 24(1):825–833. https://doi.org/10.1080/10717544.2017.1321062
Zafar N, Fessi H, Elaissari A (2014) Cyclodextrin containing biodegradable particles: from preparation to drug delivery applications. Int J Pharm 461(1):351–366. https://doi.org/10.1016/j.ijpharm.2013.12.004
Zhao L, Feng SS (2010) Enhanced oral bioavailability of paclitaxel formulated in vitamin E-TPGS emulsified nanoparticles of biodegradable polymers: in vitro and in vivo studies. J Pharm Sci 99(8):3552–3560. https://doi.org/10.1002/jps.22113
Zhao X, Deng Y, Zhang Y, Zu Y, Lian B, Wu M, Zu C, Wu W (2016) Silymarin nanoparticles through emulsion solvent evaporation method for oral delivery with high antioxidant activities, bioavailability, and absorption in the liver. RSC Adv 6(95):93137–93146. https://doi.org/10.1039/C6RA12896C
Acknowledgements
The authors wish to express their gratitude to Indian Council of Medical Research (ICMR) New Delhi, Government of India, for providing financial assistance through senior research fellowship (ICMR-SRF-2670) to Shweta Paroha.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Paroha, S., Dewangan, R.P., Dubey, R.D. et al. Conventional and nanomaterial-based techniques to increase the bioavailability of therapeutic natural products: a review. Environ Chem Lett 18, 1767–1778 (2020). https://doi.org/10.1007/s10311-020-01038-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10311-020-01038-1