Abstract
The purpose of the study was to explore the effect of different type of crosslinked cyclodextrins for the delivery of poorly soluble, photosensitive drug, resveratrol. Crosslinkers, diphenyl carbonate and pyromellitic dianhydride were used to prepare carbonyl (NS-I) and carboxylate (NS-II) crosslinked cyclodextrin respectively. The solubility and in silico molecular interaction of resveratrol with these NS at different crosslinker ratio were studied. The results showed enhanced solubility and better interaction of resveratrol with nanosponges prepared with 1:4 Cyclodextrin: crosslinker ratio. The drug-loaded nanosponges (RES-NS-I and II) prepared using 1:4 crosslinked NS-I and II were characterized using DSC, PXRD, SEM, FTIR and evaluated for particle size, zeta potential, photodegradation, in vitro drug release, in vitro cytotoxicity and in vivo oral bioavailability in rats. Physical characterization confirmed the molecular inclusion of drug with NS. The release of the drug was increased to 2.5–3 folds in the dissolution medium, with initial drug release faster with RES-NS-II. Photostability was enhanced to 2.3 fold with RES-NS-II. The cytotoxicity test exhibited 1.5 fold reduction in IC50 with drug-loaded NS. RES-NS-II exhibited 2.5 fold increase in Cmax and fourfold decrease in Tmax. Carboxylate crosslinked Cyclodextrin using pyromellitic dianhydride proves to be an effective nanocarrier for resveratrol.
Similar content being viewed by others
Abbreviations
- RES:
-
Resveratrol
- NS:
-
Nanosponge
- CD:
-
Cyclodextrin
References
Siddiqui, I.A., Sanna, V., Ahmad, N., Sechi, M., Mukhtar, H.: Resveratrol nanoformulation for cancer prevention and therapy. Ann. N. Y. Acad. Sci. 1348(1), 20–31 (2015)
Sanna, V., Siddiqui, I.A., Sechi, M., Mukhtar, H.: Resveratrol-loaded nanoparticles based on poly (epsilon-caprolactone) and poly (d, l-lactic-co-glycolic acid)–poly (ethylene glycol) blend for prostate cancer treatment. Mol. Pharm. 10(10), 3871–3881 (2013)
Summerlin, N., Soo, E., Thakur, S., Qu, Z., Jambhrunkar, S., Popat, A.: Resveratrol nanoformulations: challenges and opportunities. Int. J. Pharm. 479(2), 282–290 (2015)
Dong, Q., Yuan, H.-L., Qian, J.-J., Zhang, C.-Y., Chen, W.-D.: Preparation and in vitro–in vivo characterization of trans-resveratrol nanosuspensions. Bio-Med. Mater. Eng. 29(3), 333–345 (2018)
Nassir, A.M., Shahzad, N., Ibrahim, I.A., Ahmad, I., Md, S., Ain, M.R.: Resveratrol-loaded PLGA nanoparticles mediated programmed cell death in prostate cancer cells. Saudi Pharm. J. 26(6), 876–885 (2018)
Shen, Y., Cao, B., Snyder, N.R., Woeppel, K.M., Eles, J.R., Cui, X.T.: ROS responsive resveratrol delivery from LDLR peptide conjugated PLA-coated mesoporous silica nanoparticles across the blood–brain barrier. J. Nanobiotechnol. 16(1), 13 (2018)
Pinho, E., Grootveld, M., Soares, G., Henriques, M.: Cyclodextrins as encapsulation agents for plant bioactive compounds. Carbohydr. Polym. 101, 121–135 (2014)
Lu, Z., Cheng, B., Hu, Y., Zhang, Y., Zou, G.: Complexation of resveratrol with cyclodextrins: solubility and antioxidant activity. Food Chem. 113(1), 17–20 (2009)
Duarte, A., Martinho, A., Luís, Â, Figueiras, A., Oleastro, M., Domingues, F.C., Silva, F.: Resveratrol encapsulation with methyl-β-cyclodextrin for antibacterial and antioxidant delivery applications. LWT-Food Sci. Technol. 63(2), 1254–1260 (2015)
Troche-Pesqueira, E., Pérez-Juste, I., Navarro-Vázquez, A., Cid, M.M.: A β-cyclodextrin–resveratrol inclusion complex and the role of geometrical and electronic effects on its electronic induced circular dichroism. RSC Adv. 3(26), 10242–10250 (2013)
Swaminathan, S., Cavalli, R., Trotta, F.: Cyclodextrin-based nanosponges: a versatile platform for cancer nanotherapeutics development. Wiley Interdisc. Rev. 8(4), 579–601 (2016)
Trotta, F.: Cyclodextrin nanosponges and their applications. In: Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications, pp. 323–342. Wiley, New York (2011)
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 12(1), 279–286 (2011)
Swaminathan, S., Pastero, L., Serpe, L., Trotta, F., Vavia, P., Aquilano, D., Trotta, M., Zara, G., Cavalli, R.: Cyclodextrin-based nanosponges encapsulating camptothecin: physicochemical characterization, stability and cytotoxicity. Eur. J. Pharm. Biopharm. 74(2), 193–201 (2010)
Rao, M., Bajaj, A., Khole, I., Munjapara, G., Trotta, F.: In vitro and in vivo evaluation of β-cyclodextrin-based nanosponges of telmisartan. J. Incl. Phenom. Macrocycl. Chem. 77(1–4), 135–145 (2013)
Anandam, S., Selvamuthukumar, S.: Fabrication of cyclodextrin nanosponges for quercetin delivery: physicochemical characterization, photostability, and antioxidant effects. J. Mater. Sci. 49(23), 8140–8153 (2014)
Shringirishi, M., Mahor, A., Gupta, R., Prajapati, S.K., Bansal, K., Kesharwani, P.: Fabrication and characterization of nifedipine loaded β-cyclodextrin nanosponges: an in vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol. 41, 344–350 (2017)
Shende, P.K., Trotta, F., Gaud, R., Deshmukh, K., Cavalli, R., Biasizzo, M.: Influence of different techniques on formulation and comparative characterization of inclusion complexes of ASA with β-cyclodextrin and inclusion complexes of ASA with PMDA cross-linked β-cyclodextrin nanosponges. J. Incl. Phenom. Macrocycl. Chem. 74(1–4), 447–454 (2012)
Shende, P.K., Gaud, R., Bakal, R., Patil, D.: Effect of inclusion complexation of meloxicam with β-cyclodextrin-and β-cyclodextrin-based nanosponges on solubility, in vitro release and stability studies. Colloids Surf. B 136, 105–110 (2015)
Shende, P., Chaphalkar, R., Deshmukh, K., Gaud, R.: Physicochemical investigation of engineered nanosuspensions containing model drug, lansoprazole. J. Dispersion Sci. Technol. 37(4), 504–511 (2016)
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. 45, 45–53 (2018)
Pushpalatha, R., Selvamuthukumar, S., Kilimozhi, D.: Hierarchy analysis of different cross-linkers used for the preparation of cross-linked cyclodextrin as drug nanocarriers. Chem. Eng. Commun. 205(6), 759–771 (2018)
Trotta, F., Tumiatti, V., Cavalli, R., Rogero, C., Mognetti, B., Berta, G.: Cyclodextrin-based nanosponges as a vehicle for antitumoral drugs. WO 3656, A1 (2009)
Rao, M.R., Bhingole, R.C.: Nanosponge-based pediatric-controlled release dry suspension of Gabapentin for reconstitution. Drug Dev Ind Pharm 41(12), 2029–2036 (2015)
Mele, A., Castiglione, F., Malpezzi, L., Ganazzoli, F., Raffaini, G., Trotta, F., Rossi, B., Fontana, A., Giunchi, G.: HR MAS NMR, powder XRD and Raman spectroscopy study of inclusion phenomena in βCD nanosponges. J. Incl. Phenom. Macrocycl. Chem. 69(3–4), 403–409 (2011)
Gabr, M.M., Mortada, S.M., Sallam, M.A.: Carboxylate cross-linked cyclodextrin: a nanoporous scaffold for enhancement of rosuvastatin oral bioavailability. Eur. J. Pharm. Sci. 111, 1–12 (2018)
Higuchi, T., Connors, K.A.: Phase solubility techniques. In: Advances Analytical Chemistry and Instrumentation, vol. 4. pp. 117–212. Wiley, New York (1965)
Swaminathan, S., Vavia, P., Trotta, F., Torne, S.: Formulation of betacyclodextrin based nanosponges of itraconazole. J. Incl. Phenom. Macrocycl. Chem. 57(1–4), 89–94 (2007)
Denizot, F., Lang, R.: Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J. Immunol. Methods 89(2), 271–277 (1986)
Li, T.-P., Wong, W.-P., Chen, L.-C., Su, C.-Y., Chen, L.-G., Liu, D.-Z., Ho, H.-O., Sheu, M.-T.: Physical and pharmacokinetic characterizations of trans-resveratrol (t-Rev) encapsulated with self-assembling lecithin-based mixed polymeric micelles (sa LMPMs). Sci. Rep. 7(1), 10674 (2017)
Trotta, F., Zanetti, M., Cavalli, R.: Cyclodextrin-based nanosponges as drug carriers. Beilstein J. Org. Chem. 8, 2091 (2012)
Venuti, V., Rossi, B., Mele, A., Melone, L., Punta, C., Majolino, D., Masciovecchio, C., Caldera, F., Trotta, F.: Tuning structural parameters for the optimization of drug delivery performance of cyclodextrin-based nanosponges. Expert Opin. Drug Deliv. 14(3), 331–340 (2017)
Dora, C.P., Trotta, F., Kushwah, V., Devasari, N., Singh, C., Suresh, S., Jain, S.: Potential of erlotinib cyclodextrin nanosponge complex to enhance solubility, dissolution rate, in vitro cytotoxicity and oral bioavailability. Carbohydr. Polym. 137, 339–349 (2016)
Jeffrey, G.A., Jeffrey, G.A.: An Introduction to Hydrogen Bonding, vol. 32. Oxford University Press, New York (1997)
Brewster, M.E., Loftsson, T.: Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59(7), 645–666 (2007)
Löbenberg, R., Amidon, G.L.: Modern bioavailability, bioequivalence and biopharmaceutics classification system. New scientific approaches to international regulatory standards. Eur. J. Pharm. Biopharm. 50(1), 3–12 (2000)
Torne, S., Darandale, S., Vavia, P., Trotta, F., Cavalli, R.: Cyclodextrin-based nanosponges: effective nanocarrier for Tamoxifen delivery. Pharm. Dev. Technol. 18(3), 619–625 (2013)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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 92, 261–272 (2018). https://doi.org/10.1007/s10847-018-0843-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10847-018-0843-8