Cyclodextrin nanosponges as bioenhancers of phytochemicals
DOI:
https://doi.org/10.56782/pps.272Keywords:
cyclodextrin nanosponge, phytochemicals, bioavailability, bioenhancersAbstract
Bioavailability is the biggest obstacle to the effectiveness of biologically active compounds. Based on a set of physicochemical requirements we can determine if the compound fulfills the drug-like character and if it has the potential to become an active pharmaceutical ingredient (API) with confirmed and thoroughly examined activities. This practice is widely used in drug design of entirely new APIs, but also in search of pharmacological active substances in large compound bases such as plant-derived substances. The chemical structure diversity of plant-based compounds assures that some of them have to be well bioavailable due to good lipid membrane permeability. However, their efficiency is often limited by poor water solubility. Thus, there is a special need for bioenhancers of naturally derived compounds. In this review we present the potential of cyclodextrin nanosponges (CDNSs) as bioavailability enhancers of selected phytochemicals, namely curcumin, resveratrol, oxyresveratrol and quercetin whose very poor water solubility is the biggest obstacle to high efficiency.
Downloads
References
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Del. Rev. 1997, 23, 3-25. doi:10.1016/s0169-409x(96)00423-1. DOI: https://doi.org/10.1016/S0169-409X(96)00423-1
Veber, D.F.; Johnson, S.R.; Cheng, H.-Y.; Smith, B.R.; Ward, K.W.; Kopple, K.D. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates. J. Med. Chem. 2002, 45, 2615-2623. doi:10.1021/jm020017n. DOI: https://doi.org/10.1021/jm020017n
Amidon, G.L.; Lennernas, H.; Shah, V.P.; Crison, J.R. A theoretical basis for a biopharmaceutic drug classification - the correlation of in-vitro drug product dissolution and in-vivo bioavailability. Pharm. Res. 1995, 12, 413-420. doi:10.1023/a:1016212804288. DOI: https://doi.org/10.1023/A:1016212804288
Rajput, K.N.; Patel, K.C.; Trivedi, U.B. β-Cyclodextrin Production by Cyclodextrin Glucanotransferase from an Alkaliphile Microbacterium terrae KNR 9 Using Different Starch Substrates. Biotechnol. Res. Int. 2016, 2016, Art. No: 2034359. doi:10.1155/2016/2034359. DOI: https://doi.org/10.1155/2016/2034359
Vyas, A.; Saraf, S.; Saraf, S. Cyclodextrin based novel drug delivery systems. J. Incl. Phenom. Macrocycl. Chem. 2008, 62, 23-42. doi:10.1007/s10847-008-9456-y. DOI: https://doi.org/10.1007/s10847-008-9456-y
Chilajwar, S.V.; Pednekar, P.P.; Jadhav, K.R.; Gupta, G.J.C.; Kadam, V.J. Cyclodextrin-based nanosponges: a propitious platform for enhancing drug delivery. Expert Opin. Drug. Deliv. 2014, 11, 111-120. doi:10.1517/17425247.2014.865013. DOI: https://doi.org/10.1517/17425247.2014.865013
Loftsson, T.; Brewster, M.E. Pharmaceutical applications of cyclodextrins: basic science and product development. J. Pharm. Pharmacol. 2010, 62, 1607-1621. doi:10.1111/j.2042-7158.2010.01030.x. DOI: https://doi.org/10.1111/j.2042-7158.2010.01030.x
Pawar, S.; Shende, P.; Trotta, F. Diversity of beta-cyclodextrin-based nanosponges for transformation of actives. Int. J. Pharm. 2019, 565, 333-350. doi:10.1016/j.ijpharm.2019.05.015. DOI: https://doi.org/10.1016/j.ijpharm.2019.05.015
Jambhekar, S.S.; Breen, P. Cyclodextrins in pharmaceutical formulations I: structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov. Today 2016, 21, 356-362. doi:10.1016/j.drudis.2015.11.017. DOI: https://doi.org/10.1016/j.drudis.2015.11.017
Loftsson, T.; Brewster, M.E. Pharmaceutical applications of cyclodextrins .1. Drug solubilization and stabilization. J. Pharm. Sci. 1996, 85, 1017-1025. doi:10.1021/js950534b. DOI: https://doi.org/10.1021/js950534b
Li, D.; Ma, M. Nanoporous polymers: New nanosponge absorbent media. Filtr. Sep. 1999, 36, 26-28. doi:10.1016/S0015-1882(00)80050-6. DOI: https://doi.org/10.1016/S0015-1882(00)80050-6
Ma, M.; Li, D.Q. New organic nanoporous polymers and their inclusion complexes. Chem. Mater. 1999, 11, 872-874. doi:10.1021/cm981090y. DOI: https://doi.org/10.1021/cm981090y
Trotta, F.; Zanetti, M.; Cavalli, R. Cyclodextrin-based nanosponges as drug carriers. Beilstein J. Org. Chem. 2012, 8, 2091-2099. doi:10.3762/bjoc.8.235. DOI: https://doi.org/10.3762/bjoc.8.235
Brewster, M.E.; Loftsson, T. Cyclodextrins as pharmaccutical solubilizers. Adv. Drug Del. Rev. 2007, 59, 645-666. doi:10.1016/j.addr.2007.05.012. DOI: https://doi.org/10.1016/j.addr.2007.05.012
Loftsson, T.; Jarho, P.; Másson, M.; Järvinen, T. Cyclodextrins in drug delivery. Expert Opin. Drug. Deliv. 2005, 2, 335-351. doi:10.1517/17425247.2.1.335. DOI: https://doi.org/10.1517/17425247.2.1.335
Pyrak, B.; Rogacka-Pyrak, K.; Gubica, T.; Szeleszczuk, L. Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics. Int. J. Mol. Sci. 2024, 25(6), Art. No: 3527. doi:10.3390/ijms25063527. DOI: https://doi.org/10.3390/ijms25063527
Shoaib, Q.U.A.; Latif, S.; Ijaz, Q.A.; Afzal, H.; Siddique, M.I.; Hussain, A.; Arshad, M.S.; Bukhari, N.I.; Abbas, N. Solubility and dissolution rate enhancement of ibuprofen by cyclodextrin based carbonate nanosponges. Pak. J. Pharm. Sci. 2021, 34, 1045-1055. doi:10.36721/pjps.2021.34.3.sup.1045-1055.1.
Gaber, D.A.; Radwan, M.A.; Alzughaibi, D.A.; Alail, J.A.; Aljumah, R.S.; Aloqla, R.M.; Alkhalifah, S.A.; Abdoun, S.A. Formulation and evaluation of Piroxicam nanosponge for improved internal solubility and analgesic activity. Drug Deliv. 2023, 30(1), Art. No: 2174208. doi:10.1080/10717544.2023.2174208. DOI: https://doi.org/10.1080/10717544.2023.2174208
Mendes, C.; Meirelles, G.C.; Barp, C.G.; Assreuy, J.; Silva, M.A.S.; Ponchel, G. Cyclodextrin based nanosponge of norfloxacin: Intestinal permeation enhancement and improved antibacterial activity. Carbohydr. Polym. 2018, 195, 586-592. doi:10.1016/j.carbpol.2018.05.011. DOI: https://doi.org/10.1016/j.carbpol.2018.05.011
Rao, M.R.P.; Chaudhari, J.; Trotta, F.; Caldera, F. Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine. AAPS PharmSciTech 2018, 19, 2358-2369. doi:10.1208/s12249-018-1064-6. DOI: https://doi.org/10.1208/s12249-018-1064-6
Mashaqbeh, H.; Obaidat, R.; Al-Shar'i, N.; El-Elimat, T.; Alnabulsi, S. Weak complexation of 5-fluorouracil with beta-cyclodextrin, carbonate, and dianhydride crosslinked beta-cyclodextrin: in vitro and in silico studies. Res. Pharm. Sci. 2022, 17, 334-349. doi:10.4103/1735-5362.350235. DOI: https://doi.org/10.4103/1735-5362.350235
Argenziano, M.; Gigliotti, C.L.; Clemente, N.; Boggio, E.; Ferrara, B.; Trotta, F.; Pizzimenti, S.; Barrera, G.; Boldorini, R.; Bessone, F.; et al. Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models. Cancers 2020, 12, Art. No: 162. doi:10.3390/cancers12010162. DOI: https://doi.org/10.3390/cancers12010162
Suvarna, V.; Singh, V.; Sharma, D.; Murahari, M. Experimental and computational insight of the supramolecular complexes of Irbesartan with beta-cyclodextrin based nanosponges. J. Drug Deliv. Sci. Technol. 2021, 63, Art. No: 102494. doi:10.1016/j.jddst.2021.102494. DOI: https://doi.org/10.1016/j.jddst.2021.102494
Vij, M.; Dand, N.; Kumar, L.; Wadhwa, P.; Wani, S.U.D.; Mahdi, W.A.; Alshehri, S.; Alam, P.; Shakeel, F. Optimisation of a Greener-Approach for the Synthesis of Cyclodextrin-Based Nanosponges for the Solubility Enhancement of Domperidone, a BCS Class II Drug. Pharmaceuticals 2023, 16, Art. No: 567. doi:10.3390/ph16040567. DOI: https://doi.org/10.3390/ph16040567
Sherje, A.P.; Surve, A.; Shende, P. CDI cross-linked -cyclodextrin nanosponges of paliperidone: synthesis and physicochemical characterization. J. Mater. Sci. Mater. Med. 2019, 30, Art. No: 74. doi:10.1007/s10856-019-6268-0. DOI: https://doi.org/10.1007/s10856-019-6268-0
Bertelli, A.; Biagi, M.; Corsini, M.; Baini, G.; Cappellucci, G.; Miraldi, E. Polyphenols: From Theory to Practice. Foods 2021, 10(11), Art. No: 2595. doi:10.3390/foods10112595. DOI: https://doi.org/10.3390/foods10112595
Panahi, Y.; Fazlolahzadeh, O.; Atkin, S.L.; Majeed, M.; Butler, A.E.; Johnston, T.P.; Sahebkar, A. Evidence of curcumin and curcumin analogue effects in skin diseases: A narrative review. J. Cell. Physiol. 2019, 234, 1165-1178. doi:10.1002/jcp.27096. DOI: https://doi.org/10.1002/jcp.27096
Qureshi, S.; Shah, A.H.; Ageel, A.M. Toxicity studies on Alpinia galanga and Curcuma longa. Planta Med. 1992, 58, 124-127. doi:10.1055/s-2006-961412. DOI: https://doi.org/10.1055/s-2006-961412
Lao, C.D.; Demierre, M.F.; Sondak, V.K. Targeting events in melanoma carcinogenesis for the prevention of melanoma. Expert Rev. Anticancer Ther. 2006, 6, 1559-1568. doi:10.1586/14737140.6.11.1559. DOI: https://doi.org/10.1586/14737140.6.11.1559
Chelimela, N.; Alavala, R.; Satla, S. Curcumin - Bioavailability Enhancement by Prodrug Approach and Novel Formulations. Chem. Biodivers. 2024, 21(5), Art. No: e202302030. doi:10.1002/cbdv.202302030. DOI: https://doi.org/10.1002/cbdv.202302030
Siviero, A.; Gallo, E.; Maggini, V.; Gori, L.; Mugelli, A.; Firenzuoli, F.; Vannacci, A. Curcumin, a golden spice with a low bioavailability. J. Herb. Med. 2015, 5, 57-70. doi:10.1016/j.hermed.2015.03.001. DOI: https://doi.org/10.1016/j.hermed.2015.03.001
Pushpalatha, R.; Selvamuthukumar, S.; Kilimozhi, D. Cross-linked, cyclodextrin-based nanosponges for curcumin delivery - Physicochemical characterization, drug release, stability and cytotoxicity. J. Drug Deliv. Sci. Technol. 2018, 45, 45-53. doi:10.1016/j.jddst.2018.03.004. DOI: https://doi.org/10.1016/j.jddst.2018.03.004
Kharat, M.; Du, Z.; Zhang, G.; McClements, D.J. Physical and Chemical Stability of Curcumin in Aqueous Solutions and Emulsions: Impact of pH, Temperature, and Molecular Environment. J. Agric. Food. Chem. 2017, 65, 1525-1532. doi:10.1021/acs.jafc.6b04815. DOI: https://doi.org/10.1021/acs.jafc.6b04815
Anand, P.; Kunnumakkara, A.B.; Newman, R.A.; Aggarwal, B.B. Bioavailability of curcumin: problems and promises. Mol. Pharm. 2007, 4, 807-818. doi:10.1021/mp700113r. DOI: https://doi.org/10.1021/mp700113r
Wu, C.-F.; Yang, J.-Y.; Wang, F.; Wang, X.-X. Resveratrol: botanical origin, pharmacological activity and applications. Chinese Journal of Natural Medicines 2013, 11, 1-15. doi:10.1016/S1875-5364(13)60001-1. DOI: https://doi.org/10.1016/S1875-5364(13)60001-1
Amri, A.; Chaumeil, J.C.; Sfar, S.; Charrueau, C. Administration of resveratrol: What formulation solutions to bioavailability limitations? J. Control. Release 2012, 158, 182-193. doi:10.1016/j.jconrel.2011.09.083. DOI: https://doi.org/10.1016/j.jconrel.2011.09.083
NCBI. PubChem Compound Summary for CID 445154, Resveratrol. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Resveratrol (accessed on September 7, 2024).
Dhakar, N.K.; Matencio, A.; Caldera, F.; Argenziano, M.; Cavalli, R.; Dianzani, C.; Zanetti, M.; Lopez-Nicolas, J.M.; Trotta, F. Comparative Evaluation of Solubility, Cytotoxicity and Photostability Studies of Resveratrol and Oxyresveratrol Loaded Nanosponges. Pharmaceutics 2019, 11, Art. No: 545. doi:10.3390/pharmaceutics11100545. DOI: https://doi.org/10.3390/pharmaceutics11100545
Jagtap, S.; Meganathan, K.; Wagh, V.; Winkler, J.; Hescheler, J.; Sachinidis, A. Chemoprotective mechanism of the natural compounds, epigallocatechin-3-O-gallate, quercetin and curcumin against cancer and cardiovascular diseases. Curr. Med. Chem. 2009, 16, 1451-1462. doi:10.2174/092986709787909578. DOI: https://doi.org/10.2174/092986709787909578
Li, H.; Zhao, X.; Ma, Y.; Zhai, G.; Li, L.; Lou, H. Enhancement of gastrointestinal absorption of quercetin by solid lipid nanoparticles. J. Control. Release 2009, 133, 238-244. doi:10.1016/j.jconrel.2008.10.002. DOI: https://doi.org/10.1016/j.jconrel.2008.10.002
Ross, J.A.; Kasum, C.M. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu. Rev. Nutr. 2002, 22, 19-34. doi:10.1146/annurev.nutr.22.111401.144957. DOI: https://doi.org/10.1146/annurev.nutr.22.111401.144957
NCBI. PubChem Compound Summary for CID 5280343, Quercetin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Quercetin (accessed on September 7, 2024).
Singireddy, A.; Subramanian, S. Cyclodextrin nanosponges to enhance the dissolution profile of quercetin by inclusion complex formation. Particul. Sci. Technol. 2016, 34, 341-346. doi:10.1080/02726351.2015.1081658. DOI: https://doi.org/10.1080/02726351.2015.1081658
NCBI. PubChem Compound Summary for CID 969516, Curcumin. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Curcumin (accessed on September 7, 2024).
NCBI. PubChem Compound Summary for CID 5281717, Oxyresveratrol. Available online: https://pubchem.ncbi.nlm.nih.gov/compound/Oxyresveratrol (accessed on September 7, 2024).
Cheng, T.; Zhao, Y.; Li, X.; Lin, F.; Xu, Y.; Zhang, X.; Li, Y.; Wang, R.; Lai, L. Computation of Octanol−Water Partition Coefficients by Guiding an Additive Model with Knowledge. J. Chem. Inf. Model. 2007, 47, 2140-2148. doi:10.1021/ci700257y. DOI: https://doi.org/10.1021/ci700257y
Darandale, S.S.; Vavia, P.R. Cyclodextrin-based nanosponges of curcumin: formulation and physicochemical characterization. J. Incl. Phenom. Macrocycl. Chem. 2013, 75, 315-322. doi:10.1007/s10847-012-0186-9. DOI: https://doi.org/10.1007/s10847-012-0186-9
Gholibegloo, E.; Mortezazadeh, T.; Salehian, F.; Ramazani, A.; Amanlou, M.; Khoobi, M. Improved curcumin loading, release, solubility and toxicity by tuning the molar ratio of cross-linker to beta-cyclodextrin. Carbohydr. Polym. 2019, 213, 70-78. doi:10.1016/j.carbpol.2019.02.075. DOI: https://doi.org/10.1016/j.carbpol.2019.02.075
Ansari, K.A.; Vavia, P.R.; Trotta, F.; Cavalli, R. Cyclodextrin-Based Nanosponges for Delivery of Resveratrol: In Vitro Characterisation, Stability, Cytotoxicity and Permeation Study. AAPS PharmSciTech 2011, 12, 279-286. doi:10.1208/s12249-011-9584-3. DOI: https://doi.org/10.1208/s12249-011-9584-3
Mashaqbeh, H.; Obaidat, R.; Al-Shar'i, N. Evaluation and Characterization of Curcumin-beta-Cyclodextrin and Cyclodextrin-Based Nanosponge Inclusion Complexation. Polymers 2021, 13, Art. No: 4073. doi:10.3390/polym13234073. DOI: https://doi.org/10.3390/polym13234073
Pushpalatha, R.; Selvamuthukumar, S.; Kilimozhi, D. Carbonyl and carboxylate crosslinked cyclodextrin as a nanocarrier for resveratrol: in silico, in vitro and in vivo evaluation. J. Incl. Phenom. Macrocycl. Chem. 2018, 92, 261-272. doi:10.1007/s10847-018-0843-8. DOI: https://doi.org/10.1007/s10847-018-0843-8
Anandam, S.; Selvamuthukumar, S. Fabrication of cyclodextrin nanosponges for quercetin delivery: physicochemical characterization, photostability, and antioxidant effects. J. Mater. Sci. 2014, 49, 8140-8153. doi:10.1007/s10853-014-8523-6. DOI: https://doi.org/10.1007/s10853-014-8523-6
Mashaqbeh, H.; Obaidat, R.; Al-shar'i, N.A. Evaluation of EDTA Dianhydride Versus Diphenyl Carbonate Nanosponges for Curcumin. AAPS PharmSciTech 2022, 23, Art. No: 229. doi:10.1208/s12249-022-02372-z. DOI: https://doi.org/10.1208/s12249-022-02372-z
Rafati, N.; Zarrabi, A.; Caldera, F.; Trotta, F.; Ghias, N. Pyromellitic dianhydride crosslinked cyclodextrin nanosponges for curcumin controlled release; formulation, physicochemical characterization and cytotoxicity investigations. J. Microencapsul. 2019, 36, 715-727. doi:10.1080/02652048.2019.1669728. DOI: https://doi.org/10.1080/02652048.2019.1669728
Pushpalatha, R.; Selvamuthukumar, S.; Kilimozhi, D. Cyclodextrin nanosponge based hydrogel for the transdermal co-delivery of curcumin and resveratrol: Development, optimization, in vitro and ex vivo evaluation. J. Drug Deliv. Sci. Technol. 2019, 52, 55-64. doi:10.1016/j.jddst.2019.04.025. DOI: https://doi.org/10.1016/j.jddst.2019.04.025
Matencio, A.; Dhakar, N.K.; Bessone, F.; Musso, G.; Cavalli, R.; Dianzani, C.; Garcia-Carmona, F.; Lopez-Nicolas, J.M.; Trotta, F. Study of oxyresveratrol complexes with insoluble cyclodextrin based nanosponges: Developing a novel way to obtain their complexation constants and application in an anticancer study. Carbohydr. Polym. 2020, 231, Art. No: 115763. doi:10.1016/j.carbpol.2019.115763. DOI: https://doi.org/10.1016/j.carbpol.2019.115763
Gharakhloo, M.; Sadjadi, S.; Rezaeetabar, M.; Askari, F.; Rahimi, A. Cyclodextrin‐Based Nanosponges for Improving Solubility and Sustainable Release of Curcumin. ChemistrySelect 2020, 5, 1734-1738. doi:10.1002/slct.201904007. DOI: https://doi.org/10.1002/slct.201904007
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Bartłomiej Pyrak, Tomasz Gubica, Karolina Rogacka-Pyrak
This work is licensed under a Creative Commons Attribution 4.0 International License.
For all articles published in Prospects in Pharmaceutical Sciences copyright is retained by the authors. The journal publishes articles in the Open Access policy, within the CC BY 4.0 licence.
This is a human-readable summary of (and not a substitute for) the license. Disclaimer.
You are free to:
Share — copy and redistribute the material in any medium or format
Adapt — remix, transform, and build upon the material for any purpose, even commercially.
The licensor cannot revoke these freedoms as long as you follow the license terms.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
How to Cite
