Generic placeholder image

Current Pharmaceutical Biotechnology

Author(s): Rattakorn Boontawee, Ousanee Issarachot, Kanidta Kaewkroek and Ruedeekorn Wiwattanapatapee*

DOI: 10.2174/1389201022666210615115553

DownloadDownload PDF Flyer Cite As
Foldable/Expandable Gastro-retentive Films Based on Starch and Chitosan as a Carrier For Prolonged Release of Resveratrol

Page: [1009 - 1018] Pages: 10

  • * (Excluding Mailing and Handling)

Abstract

Background: Resveratrol exerts a number of therapeutic effects, notably antiinflammatory, antioxidant and anti-cancer activities which are beneficial for the treatment of gastric diseases. However, the efficacy of resveratrol is severely limited due to the poor aqueous solubility and rapid metabolism following oral administration. As a result, foldable/expandable devices based on natural polymers merging with solid dispersion technology have been developed to increase the solubility, prolong the gastric residence time, and provide a controlled release therapy of resveratrol.

Objectives: This research aimed to invent foldable/expandable films based on natural polymers, including starch and chitosan, for stomach-specific delivery and prolonged release of resveratrol.

Methods: The films were prepared by solvent casting using either rice, tapioca, corn starch or pregelatinized corn starch combined with chitosan in different weight to weight ratios. Glycerol was included as a plasticizer. Resveratrol solid dispersions (Res-SD) prepared by solvent evaporation and employing PVP-K30 as a hydrophilic polymer were loaded into the polymeric film, which was subsequently folded prior to insertion in a hard gelatin capsule.

Results: The solid dispersions improved the solubility of resveratrol by a factor of 500. All Res-SD loaded film formulations completely unfolded in simulated gastric fluid at 37oC within 10 min. Fluid absorption by the films was influenced by the ratio of amylose and amylopectin in the starch granules, with tapioca starch formulations displaying the highest fluid uptake. Films prepared from pregelatinized corn starch and chitosan resulted in highly efficient delivery of resveratrol, with more than 80%of the content released over a period of 12 hrs. Furthermore, the released polyphenol exhibited cytotoxic activity against human gastric adenocarcinoma cells and anti-inflammatory effects against lipopolysaccharide-stimulated murine, macrophage-like cells.

Conclusions: These findings demonstrate the potential of foldable/expandable films based on natural polymers as a promising stomach-specific carrier for improving the treatment of gastric disorders.

Keywords: Resveratrol, chitosan, rice starch, tapioca starch, corn starch, gastro-retentive drug delivery systems.

Graphical Abstract

[1]
Summerlin, N.; Soo, E.; Thakur, S.; Qu, Z.; Jambhrunkar, S.; Popat, A. Resveratrol nanoformulations: Challenges and opportunities. Int. J. Pharm., 2015, 479(2), 282-290.
[http://dx.doi.org/10.1016/j.ijpharm.2015.01.003 ] [PMID: 25572692]
[2]
de la Lastra, C.A.; Villegas, I. Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Mol. Nutr. Food Res., 2005, 49(5), 405-430.
[http://dx.doi.org/10.1002/mnfr.200500022 ] [PMID: 15832402]
[3]
Sun, A.Y.; Wang, Q.; Simonyi, A.; Sun, G.Y. Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol. Neurobiol., 2010, 41(2-3), 375-383.
[http://dx.doi.org/10.1007/s12035-010-8111-y ] [PMID: 20306310]
[4]
Bonnefont-Rousselot, D. Resveratrol and cardiovascular diseases. Nutrients, 2016, 8(5), 250.
[http://dx.doi.org/10.3390/nu8050250 ] [PMID: 27144581]
[5]
Gambini, J.; Inglés, M.; Olaso, G.; Lopez-Grueso, R.; Bonet-Costa, V.; Gimeno-Mallench, L.; Mas-Bargues, C.; Abdelaziz, K.M.; Gomez-Cabrera, M.C.; Vina, J.; Borras, C. Properties of resveratrol: In vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxid. Med. Cell. Longev., 2015, 2015837042
[http://dx.doi.org/10.1155/2015/837042 ] [PMID: 26221416]
[6]
Szkudelski, T.; Szkudelska, K. Resveratrol and diabetes: From animal to human studies. Biochim. Biophys. Acta, 2015, 1852(6), 1145-1154.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.013 ] [PMID: 25445538]
[7]
de Ligt, M.; Timmers, S.; Schrauwen, P. Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? Biochim. Biophys. Acta, 2015, 1852(6), 1137-1144.
[http://dx.doi.org/10.1016/j.bbadis.2014.11.012 ] [PMID: 25446988]
[8]
Aluyen, J.K.; Ton, Q.N.; Tran, T.; Yang, A.E.; Gottlieb, H.B.; Bellanger, R.A. Resveratrol: Potential as anticancer agent. J. Diet. Suppl., 2012, 9(1), 45-56.
[http://dx.doi.org/10.3109/19390211.2011.650842 ] [PMID: 22432802]
[9]
Poulsen, M.M.; Fjeldborg, K.; Ornstrup, M.J.; Kjær, T.N.; Nøhr, M.K.; Pedersen, S.B. Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes. Biochim. Biophys. Acta, 2015, 1852(6), 1124-1136.
[http://dx.doi.org/10.1016/j.bbadis.2014.12.024 ] [PMID: 25583116]
[10]
Pangeni, R.; Sahni, J.K.; Ali, J.; Sharma, S.; Baboota, S. Resveratrol: Review on therapeutic potential and recent advances in drug delivery. Expert Opin. Drug Deliv., 2014, 11(8), 1285-1298.
[http://dx.doi.org/10.1517/17425247.2014.919253 ] [PMID: 24830814]
[11]
Yang, Q.; Wang, B.; Zang, W.; Wang, X.; Liu, Z.; Li, W.; Jia, J. Resveratrol inhibits the growth of gastric cancer by inducing G1 phase arrest and senescence in a Sirt1-dependent manner. PLoS One, 2013, 8(11)e70627
[http://dx.doi.org/10.1371/journal.pone.0070627 ] [PMID: 24278101]
[12]
Guha, P.; Dey, A.; Chatterjee, A.; Chattopadhyay, S.; Bandyopadhyay, S.K. Pro-ulcer effects of resveratrol in mice with indomethacin-induced gastric ulcers are reversed by L-arginine. Br. J. Pharmacol., 2010, 159(3), 726-734.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00572.x ] [PMID: 20067468]
[13]
Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov., 2006, 5(6), 493-506.
[http://dx.doi.org/10.1038/nrd2060 ] [PMID: 16732220]
[14]
Lee, D.U.; Kim, H.M.; Lee, G.D.; Jeon, S.H.; Lee, J.J.; Lee, S.H. Effects of thermal treatments on the stability of trans-resveratrol and yeast inactivation in trans-resveratrol-amplified grape juice. Arch. Biol. Sci., 2014, 66(1), 323-329.
[http://dx.doi.org/10.2298/ABS1401323L]
[15]
Mehta, M.; Neeta, S.; Pandey, P.; Mahajan, S.; Satija, S. Gastro retentive drug delivery systems: An overview. Research J Pharm and Tech, 2018, 11(5), 2157-2160.
[http://dx.doi.org/10.5958/0974-360X.2018.00398.0]
[16]
Sivaneswariab, S.; Karthikeyanac, E.; Chandanaa, P.J. Novel expandable gastro retentive system by unfolding mechanism of levetiracetam using simple lattice design formulation optimization and in vitro evaluation. Bull. Fac. Pharm. Cairo Univ., 2017, 55(1), 63-72.
[http://dx.doi.org/10.1016/j.bfopcu.2017.02.003]
[17]
Sathish, D.; Himabindu, S.; Kumar, P.P.; Rao, Y.M. Preparation and evaluation of novel expandable drug delivery system. Br. J. Pharm. Res., 2013, 3(4), 1079-1093.
[http://dx.doi.org/10.9734/BJPR/2013/4891]
[18]
Ullah, M.B.; Karim, M.R.; Alam, M.S.; Hassan, R.; Bhuiyan, M.; Rana, M. Formulation and in vitro evaluation of unfolding type expandable gastroretentive film of Enalapril maleate. Bangladesh Pharm J., 2017, 20(2), 148-154.
[http://dx.doi.org/10.3329/bpj.v20i2.37868]
[19]
Verma, S.; Nagpal, K.; Singh, S.K.; Mishra, D.N. Unfolding type gastroretentive film of Cinnarizine based on ethyl cellulose and hydroxypropylmethyl cellulose. Int. J. Biol. Macromol., 2014, 64, 347-352.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.12.030 ] [PMID: 24370473]
[20]
Lenson, D.; Marina, K. Bilayer film type of unfolding drug delivery system for the dual release of proton pump inhibitor and H2 receptor antagonist. Asian J Pharm, 2016, 10(2), S76-S85.
[21]
Bansal, V.; Sharma, P.K.; Sharma, N.; Pal, O.P.; Malviya, R. Applications of chitosan and chitosan derivatives in drug delivery. Adv. Biol. Res. (Faisalabad), 2011, 5(1), 28-37.
[22]
Builders, P.F.; Arhewoh, M.I. Pharmaceutical applications of native starch in conventional drug delivery. Starke, 2016, 68, 1-10.
[http://dx.doi.org/10.1002/star.201500337]
[23]
Wang, B.; Wang, D.; Zhao, S.; Huang, X.; Zhang, J.; Lv, Y.; Liu, X.; Lv, G.; Ma, X. Evaluate the ability of PVP to inhibit crystallization of amorphous solid dispersions by density functional theory and experimental verify. Eur. J. Pharm. Sci., 2017, 96, 45-52.
[http://dx.doi.org/10.1016/j.ejps.2016.08.046 ] [PMID: 27568852]
[24]
Klausner, E.A.; Lavy, E.; Barta, M.; Cserepes, E.; Friedman, M.; Hoffman, A. Novel gastroretentive dosage forms: Evaluation of gastroretentivity and its effect on levodopa absorption in humans. Pharm. Res., 2003, 20(9), 1466-1473.
[http://dx.doi.org/10.1023/A:1025770530084 ] [PMID: 14567643]
[25]
Sapkal, S.; Babhulkar, M.; Rathi, A. An overview on the mechanisms of solubility and dissolution rate enhancement in solid dispersion. Int. J. Pharm. Tech. Res., 2013, 5(1), 31-39.
[26]
Rashid, I.; Al Omari, M.H.; Leharne, S.A.; Chowdhry, B.Z.; Badwan, A. From native to multifunctional starch-based excipients designed for direct compression formulation. Starke, 2013, 65, 552-571.
[http://dx.doi.org/10.1002/star.201200297]
[27]
Rashid, I.; Al Omari, M.H.; Leharne, S.A.; Chowdhry, B.Z.; Badwan, A. Starch gelatinization using sodium silicate: FTIR, DSC, XRPD, and NMR studies. Starke, 2012, 64(9), 713-728.
[http://dx.doi.org/10.1002/star.201100190]
[28]
Yuan, Y.; Zhang, L.; Dai, Y.; Yu, J. Physicochemical properties of starch obtained from Dioscorea nipponica Makino comparison with other tuber starches. J. Food Eng., 2007, 82(4), 436-442.
[http://dx.doi.org/10.1016/j.jfoodeng.2007.02.055]
[29]
Sinnott, M. Carbohydrate Chemistry and Biochemistry: Structure and Mechanism, 1st ed.; The royal society of chemistry: London, , 2007.
[30]
Beneke, C.E.; Viljoen, A.M.; Hamman, J.H. Polymeric plant-derived excipients in drug delivery. Molecules, 2009, 14(7), 2602-2620.
[http://dx.doi.org/10.3390/molecules14072602 ] [PMID: 19633627]
[31]
Huang, Y.; Dai, W.G. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm. Sin. B, 2014, 4(1), 18-25.
[http://dx.doi.org/10.1016/j.apsb.2013.11.001 ] [PMID: 26579360]
[32]
Lefnaoui, S.; Moulai-Mostefa, N. Synthesis and evaluation of the structural and physicochemical properties of carboxymethyl pregelatinized starch as a pharmaceutical excipient. Saudi Pharm. J., 2015, 23(6), 698-711.
[http://dx.doi.org/10.1016/j.jsps.2015.01.021 ] [PMID: 26702266]
[33]
Baklagina, Y.G.; Klechkovskaya, V.V.; Kononova, S.V.; Petrova, V.A.; Poshina, D.N.; Orekhov, A.S.; Skorik, Y.A. Polymorphic modifications of chitosan. Crystallogr. Rep., 2018, 63(3), 303-313.
[http://dx.doi.org/10.1134/S1063774518030033]
[34]
Plöger, G.F.; Hofsäss, M.A.; Dressman, J.B. Solubility determination of active pharmaceutical ingredients which have been recently added to the list of essential medicines in the context of the biopharmaceutics classification system biowaiver. J. Pharm. Sci., 2018, 107(6), 1478-1488.
[http://dx.doi.org/10.1016/j.xphs.2018.01.025 ] [PMID: 29421214]
[35]
Uddin, R.; Saffoon, N.; Sutradhar, K.B. Dissolution and dissolution apparatus: A Review. Int J Cur Biomed Phar Res., 2011, 1(4), 201-207.
[36]
Kaewkroek, K.; Wattanapiromsakul, C.; Kongsaeree, P.; Tewtrakul, S. Nitric oxide and tumor necrosis factor-alpha inhibitory substances from the rhizomes of Kaempferia marginata. Nat. Prod. Commun., 2013, 8(9), 1205-1208.
[http://dx.doi.org/10.1177/1934578X1300800904 ] [PMID: 24273846]
[37]
Elsabee, M.Z.; Abdou, E.S. Chitosan based edible films and coatings: a review. Mater. Sci. Eng. C, 2013, 33(4), 1819-1841.
[http://dx.doi.org/10.1016/j.msec.2013.01.010 ] [PMID: 23498203]
[38]
Shapi’i, R.A.; Othman, S.H. Effect of concentration of chitosan on the mechanical, morphological and optical properties of tapioca starch film. Int Food Res., 2016, 23(Suppl.), S187-S193.
[39]
Alcázar-Alay, S.C.; Meireles, M.A.A. Physicochemical properties, modifications and applications of starches from different botanical sources. Food Sci. Technol. (Campinas), 2015, 35(2), 215-236.
[http://dx.doi.org/10.1590/1678-457X.6749]
[40]
Domene-López, D.; García-Quesada, J.C.; Martin-Gullon, I.; Montalbán, M.G. Influence of starch composition and molecular weight on physicochemical properties of biodegradable films. Polymers (Basel), 2019, 11(7), 1084.
[http://dx.doi.org/10.3390/polym11071084 ] [PMID: 31247882]
[41]
Na Nakorn, K.; Tongdang, T.; Sirivongpaisala, P. Crystallinity and rheological properties of pregelatinized rice starches differing in amylose content. Starke, 2009, 61, 101-108.
[http://dx.doi.org/10.1002/star.200800008]