Abstract
The use of natural compounds in medicine for the treatment of diseases started since ancient days. Though many natural compounds exhibit potent pharmacological activity, their medicinal application is limited by low solubility, permeability or stability. Therefore, pharmaceutical scientists are developing drug delivery systems and carriers that allow better efficacy and clinical success. For instance, nanocarriers, owing to their small size and unique surface properties, allow successful delivery of various drugs by modifying solubility, permeability and pharmacokinetics. Nanocarriers preserve encapsulated molecules from degradation and, in turn, enhance stability. Here, we review nanocarriers with focus on natural molecules including thymoquinone, resveratrol, artemisinin, silymarin, natural antibiotics and natural extracts, which are used in different disease conditions, for example Alzheimer’s, diabetes, microbial infections, inflammation and psoriasis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- AUC:
-
Area under the curve
- EGCG:
-
Epigallocatechin-3-gallate
- NLC:
-
Nanostructured lipid carrier
- PLGA:
-
Poly(lactic-co-glycolic acid)
- SLN:
-
Solid lipid nanoparticle
- NLC:
-
Nanostructured lipid carrier
References
Ansari KA, Vavia PR, Trotta F, Cavalli R (2011) Cyclodextrin-based nanosponges for delivery of resveratrol: in vitro characterisation, stability, cytotoxicity and permeation study. AAPS PharmSciTech 12(1):279–286. https://doi.org/10.1208/s12249-011-9584-3
Avadhani KS, Manikkath J, Tiwari M et al (2017) Skin delivery of epigallocatechin-3-gallate (EGCG) and hyaluronic acid loaded nano-transfersomes for antioxidant and anti-aging effects in UV radiation induced skin damage. Drug Deliv 24:61–74. https://doi.org/10.1080/10717544.2016.1228718
Badary OA, Al-Shabanah OA, Nagi MN et al (1998) Acute and subchronic toxicity of thymoquinone in mice. Drug Dev Res 44(2–3):56–61. https://doi.org/10.1002/(SICI)1098-2299(199806/07)44:2/3<56:AID-DDR2>3.0.CO;2-9
Barenholz Y (2012) Doxil®—The first FDA-approved nano-drug: lessons learned. J Control Release 160(2):117–134. https://doi.org/10.1016/j.jconrel.2012.03.020
Battaglia L, D’Addino I, Peira E et al (2012) Solid lipid nanoparticles prepared by coacervation method as vehicles for ocular cyclosporine. J Drug Deliv Sci Technol 22(2):125–130. https://doi.org/10.1016/S1773-2247(12)50016-X
Bilia AR, Piazzini V, Guccione C et al (2017) Improving on nature: the role of nanomedicine in the development of clinical natural drugs. Planta Med 83(05):366–381. https://doi.org/10.1055/s-0043-102949
Boisseau P, Loubaton B (2011) Nanomedicine, nanotechnology in medicine. C R Phys 12(7):620–636. https://doi.org/10.1016/j.crhy.2011.06.001
Borel JF, Feurer C, Gubler HU, Stähelin H (1994) Biological effects of cyclosporin A: a new antilymphocytic agent. Agents Actions 43(3–4):179–186. https://doi.org/10.1007/BF01986686
Caddeo C, Teskač K, Sinico C, Kristl J (2008) Effect of resveratrol incorporated in liposomes on proliferation and UV-B protection of cells. Int J Pharm 363(1–2):183–191. https://doi.org/10.1016/j.ijpharm.2008.07.024
Cano A, Ettcheto M, Chang JH et al (2019) Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer’s disease mice model. J Control Release 301:62–75. https://doi.org/10.1016/j.jconrel.2019.03.010
Chauhan MK, Bhatt N (2019) Bioavailability enhancement of Polymyxin B With novel drug delivery: development and optimization using quality-by-design approach. J Pharm Sci 108(4):1521–1528. https://doi.org/10.1016/j.xphs.2018.11.032
Coppi G, Iannuccelli V, Sala N, Bondi M (2004) Alginate microparticles for Polymyxin B Peyer’s patches uptake: microparticles for antibiotic oral administration. J Microencapsul 21(8):829–839. https://doi.org/10.1080/02652040400015437
Dag D, Oztop MH (2017) Formation and characterization of green tea extract loaded liposomes. J Food Sci 82(2):463–470. https://doi.org/10.1111/1750-3841.13615
Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2(2):303–336. https://doi.org/10.3390/metabo2020303
Dwivedi P, Khatik R, Khandelwal K et al (2014) Pharmacokinetics study of arteether loaded solid lipid nanoparticles: an improved oral bioavailability in rats. Int J Pharm 466(1–2):321–327. https://doi.org/10.1016/j.ijpharm.2014.03.036
Erlund I (2004) Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 24(10):851–874. https://doi.org/10.1016/j.nutres.2004.07.005
Frémont L (2000) Minireview: biological effects of resveratrol. Life Sci 66(8):663–673. https://doi.org/10.1016/S0024-3205(99)00410-5
Gauttam VK, Kalia AN (2013) Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system. J Adv Pharm Technol Res 4(2):108. https://doi.org/10.4103/2231-4040.111527
Gharib A, Faezizadeh Z, Godarzee M (2013) Therapeutic efficacy of epigallocatechin gallate-loaded nanoliposomes against burn wound infection by methicillin-resistant staphylococcus aureus. Skin Pharmacol Physiol 26:68–75. https://doi.org/10.1159/000345761
Gholamnezhad Z, Havakhah S, Boskabady MH (2016) Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: a review. J Ethnopharmacol 190:372–386. https://doi.org/10.1016/j.jep.2016.06.061
Gupta L, Sharma AK, Gothwal A et al (2017) Dendrimer encapsulated and conjugated delivery of berberine: a novel approach mitigating toxicity and improving in vivo pharmacokinetics. Int J Pharm 528:88–99. https://doi.org/10.1016/j.ijpharm.2017.04.073
Haddadi A, Elamanchili P, Lavasanifar A et al (2008) Delivery of rapamycin by PLGA nanoparticles enhances its suppressive activity on dendritic cells. J Biomed Mater Res Part A 84:885–898. https://doi.org/10.1002/jbm.a.31373
Ibrahim N, Ibrahim H, Sabater AM et al (2015) Artemisinin nanoformulation suitable for intravenous injection: preparation, characterization and antimalarial activities. Int J Pharm 495(2):671–679. https://doi.org/10.1016/j.ijpharm.2015.09.020
Isacchi B, Arrigucci S, La MG et al (2011) Conventional and long-circulating liposomes of artemisinin: preparation, characterization, and pharmacokinetic profile in mice. J Liposome Res 21(3):237–244. https://doi.org/10.3109/08982104.2010.539185
Joshi M, Pathak S, Sharma S, Patravale V (2008) Design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: nanoject. Int J Pharm 364(1):119–126. https://doi.org/10.1016/j.ijpharm.2008.07.032
Kakran M, Sahoo NG, Li L, Judeh Z (2010) Dissolution of artemisinin/polymer composite nanoparticles fabricated by evaporative precipitation of nanosuspension. J Pharm Pharmacol 62:413–421. https://doi.org/10.1211/jpp.62.04.0002
Kaur H, Kumar B, Chakrabarti A et al (2018) A New Therapeutic approach for brain delivery of epigallocatechin gallate: development and characterization studies. Curr Drug Deliv 16:59–65. https://doi.org/10.2174/1567201815666180926121104
Kausar H, Mujeeb M, Ahad A et al (2019) Optimization of ethosomes for topical thymoquinone delivery for the treatment of skin acne. J Drug Deliv Sci Technol 49:177–187. https://doi.org/10.1016/j.jddst.2018.11.016
Khan AW, Kotta S, Ansari SH et al (2015) Self-nanoemulsifying drug delivery system (SNEDDS) of the poorly water-soluble grapefruit flavonoid naringenin: design, characterization, in vitro and in vivo evaluation. Drug Deliv 22(4):552–561. https://doi.org/10.3109/10717544.2013.878003
Klockgether-Radke AP (2002) F. W. Sertürner and the discovery of morphine. 200 Years of pain therapy with opioids. Anasthesiol Intensivmed Notfallmedizin Schmerzther 37(5):244. https://doi.org/10.1055/s-2002-30132
Krishna S, Bustamante L, Haynes RK, Staines HM (2008) Artemisinins: their growing importance in medicine. Trends Pharmacol Sci 29(10):520–527. https://doi.org/10.1016/j.tips.2008.07.004
Kumar RP, Abraham A (2016) PVP-coated naringenin nanoparticles for biomedical applications—in vivo toxicological evaluations. Chem Biol Interact 257:110–118. https://doi.org/10.1016/j.cbi.2016.07.012
Lapenna S, Bilia AR, Morris GA, Nilsson M (2009) Novel artemisinin and curcumin micellar formulations: drug solubility studies by NMR spectroscopy. J Pharm Sci 98(10):3666–3675. https://doi.org/10.1002/jps.21685
Loureiro JA, Andrade S, Duarte A et al (2017) Resveratrol and grape extract-loaded solid lipid nanoparticles for the treatment of Alzheimer’s disease. Molecules 22(2):277. https://doi.org/10.3390/molecules22020277
Lutsenko SV, Gromovykh TI, Krasnyuk II et al (2018) Antihepatotoxic activity of liposomal silibinin. Bionanoscience. 8(2):581–586. https://doi.org/10.1007/s12668-018-0512-9
Maas J, Kamm W, Hauck G (2007) An integrated early formulation strategy—from hit evaluation to preclinical candidate profiling. Eur J Pharm Biopharm 66(1):1–10. https://doi.org/10.1016/j.ejpb.2006.09.011
Marchiori MCL, Rigon C, Camponogara C et al (2017) Hydrogel containing silibinin-loaded pomegranate oil based nanocapsules exhibits anti-inflammatory effects on skin damage UVB radiation-induced in mice. J Photochem Photobiol B Biol 170:25–32. https://doi.org/10.1016/j.jphotobiol.2017.03.015
Müller R, Runge S, Ravelli V, Mehnert W, Thünemann AF, Souto E (2006) Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN®) versus drug nanocrystals. Int J Pharm 317(1):82–89. https://doi.org/10.1016/j.ijpharm.2006.02.045
Nallamuthu I, Parthasarathi A, Khanum F (2013) Thymoquinone-loaded PLGA nanoparticles: antioxidant and anti-microbial properties. Int Curr Pharm J 2(12):202–207. https://doi.org/10.3329/icpj.v2i12.17017
Portman RJ, Meier-Kriesche HU, Swinford R et al (2000) Reduced variability of neoral pharmacokinetic studies in pediatric renal transplantation. Pediatr Nephrol 15:2–6. https://doi.org/10.1007/s004670000435
Rani R, Dahiya S, Dhingra D et al (2017) Evaluation of anti-diabetic activity of glycyrrhizin-loaded nanoparticles in nicotinamide-streptozotocin-induced diabetic rats. Eur J Pharm Sci 106:220–230. https://doi.org/10.1016/j.ejps.2017.05.068
Ripoli M, Angelico R, Sacco P et al (2016) Phytoliposome-based silibinin delivery system as a promising strategy to prevent hepatitis C virus infection. J Biomed Nanotechnol 12(4):770–780. https://doi.org/10.1166/jbn.2016.2161
Sahibzada MUK, Sadiq A, Sfaidah H et al (2018) Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity. Drug Des Dev Ther 12:303. https://doi.org/10.2147/DDDT.S156123
Sahoo NG, Kakran M, Shaal LA et al (2011) Preparation and characterization of quercetin nanocrystals. J Pharm Sci 100:2379–2390. https://doi.org/10.1002/jps.22446
Saka R, Chella N (2020) Nanocarriers as tools for delivery of nature derived compounds and extracts with therapeutic activity. In: Saneja A, Panda A, Lichtfouse E (eds) Sustainable agriculture reviews, vol 44. Springer, Cham, pp 73–114. https://doi.org/10.1007/978-3-030-41842-7_3
Shetty PK, Manikkath J, Tupally K et al (2017) Skin delivery of EGCG and silibinin: potential of peptide dendrimers for enhanced skin permeation and deposition. AAPS PharmSciTech 18:2346–2357. https://doi.org/10.1208/s12249-017-0718-0
Su XZ, Miller LH (2015) The discovery of artemisinin and the nobel prize in physiology or medicine. Sci China Life Sci 58:1175–1179. https://doi.org/10.1007/s11427-015-4948-7
Tan Q, Liu W, Guo C, Zhai G (2011) Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery. Int J Nanomed 6:1621. https://doi.org/10.2217/nnm.11.142
Tsai MJ, Bin HY, Fang JW et al (2015) Preparation and evaluation of submicron-carriers for naringenin topical application. Int J Pharm 481(1–2):84–90. https://doi.org/10.1016/j.ijpharm.2015.01.034
Valenzuela A, Garrido A (1994) Biochemical bases of the pharmacological action of the flavonoid silymarin and of its structural isomer silibinin. Biol Res 27:105–105
Walunj M, Doppalapudi S, Bulbake U, Khan W (2020) Preparation, characterization, and in vivo evaluation of cyclosporine cationic liposomes for the treatment of psoriasis. J Liposome Res 30(1):68–79. https://doi.org/10.1080/08982104.2019.1593449
Wang L, Zhao X, Zu Y et al (2016) Enhanced dissolution rate and oral bioavailability of ginkgo biloba extract by preparing nanoparticles: via emulsion solvent evaporation combined with freeze drying (ESE-FR). RSC Adv 6(81):77346–77357. https://doi.org/10.1039/c6ra14771b
Wu CY, Benet LZ, Hebert MF et al (1995) Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther 58(5):492–497. https://doi.org/10.1016/0009-9236(95)90168-X
Yen FL, Wu TH, Lin LT et al (2008) Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats. Food Chem Toxicol 46(5):1771–1777. https://doi.org/10.1016/j.fct.2008.01.021
Yuan H, Ma Q, Ye L, Piao G (2016) The traditional medicine and modern medicine from natural products. Molecules 21(5):559. https://doi.org/10.3390/molecules21050559
Zakeri-Milani P, Loveymi BD, Jelvehgari M, Valizadeh H (2013) The characteristics and improved intestinal permeability of vancomycin PLGA-nanoparticles as colloidal drug delivery system. Colloids Surf B Biointerfaces 103:174–181. https://doi.org/10.1016/j.colsurfb.2012.10.021
Zhang J, Nie S, Wang S (2013) Nanoencapsulation enhances epigallocatechin-3-gallate stability and its antiatherogenic bioactivities in macrophages. J Agric Food Chem 61:9200–9209. https://doi.org/10.1021/jf4023004
Zhang J, Zhou X, Yu Q et al (2014) Epigallocatechin-3-gallate (EGCG)-stabilized selenium nanoparticles coated with Tet-1 peptide to reduce amyloid-β aggregation and cytotoxicity. ACS Appl Mater Interfaces 6(11):8475–8487. https://doi.org/10.1021/am501341u
Zhou Y, Liu SQ, Peng H et al (2015) In vivo anti-apoptosis activity of novel berberine-loaded chitosan nanoparticles effectively ameliorates osteoarthritis. Int Immunopharmacol 28:34–43. https://doi.org/10.1016/j.intimp.2015.05.014
Zou W, Cao G, Xi Y, Zhang N (2009) New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles. Drug Deliv 16(1):15–23. https://doi.org/10.1080/10717540802481307
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
Saka, R., Chella, N. Nanotechnology for delivery of natural therapeutic substances: a review. Environ Chem Lett 19, 1097–1106 (2021). https://doi.org/10.1007/s10311-020-01103-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10311-020-01103-9