Abstract
Curcumin was modified with 2-hydroxypropyl-\(\beta\)-cyclodextrin (HP\(\beta\)CD) to enhance its bioavailability. The modified curcumin was loaded into gelatin-carrageenan microparticles to control the drug release behavior. The different analytical techniques like Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy (RS), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) indicated the formation of the samples. The solubility of the modified curcumin was checked visibly and by using UV-VIS spectroscopy & optical microscopy as well. The effect of surfactant on process yield, drug loading & encapsulation efficiency, swelling and drug release from the microparticles was checked. The samples exhibited more swelling and hence drug release was more in basic compared to acidic medium and the percentage increased with increase in time. The modified curcumin, on examining in both breast and lung cancer cell lines, manifested better anticancer activity compared to curcumin as evidenced by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, clonogenic assay and apoptosis assay. However, the microparticles didn’t reveal better anticancer activities compared to curcumin and modified curcumin. Further, all the prepared samples were found to be non-toxic to human peripheral blood mononuclear cells (PBMCs) and red blood cells (RBCs).
Graphical Abstract
Similar content being viewed by others
Data Availability
The datasets generated during and/or analysed during the current study are not publicly available due to some pending research work using the data
References
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;213:70–8.
Mujokoro B, Madani F, Esnaashari SS, Khosravani M, Adabi M. Combination and co-delivery of methotrexate and curcumin: preparation and in vitro cytotoxic investigation on glioma cells. J Pharm Innov. 2019:1–10.
Bakre LG, Sarvaiya JI, Agrawal YK. Synthesis, characterization, and study of drug release properties of curcumin from polycaprolactone/organomodified montmorillonite nanocomposite. J Pharm Innov. 2016;11(4):300–7.
Youssouf L, Bhaw-Luximon A, Diotel N, Catan A, Giraud P, Gimié F, Koshel D, Casale S, Bénard S, Meneyrol V, et al. Enhanced effects of curcumin encapsulated in polycaprolactone-grafted oligocarrageenan nanomicelles, a novel nanoparticle drug delivery system. Carbohydr Polym. 2019;217:35–45.
Wathoni N, Motoyama K, Higashi T, Okajima M, Kaneko T, Arima H. Enhancement of curcumin wound healing ability by complexation with 2-hydroxypropyl-\(\gamma\)-cyclodextrin in sacran hydrogel film. Int J Biol Macromol. 2017;98:268–76.
Kaur K, Uppal S, Kaur R, Agarwal J, Mehta SK. Energy efficient, facile and cost effective methodology for formation of an inclusion complex of resveratrol with hp-\(\beta\)-cd. New J Chem. 2015;39(11):8855–65.
Sun J, Hong H, Zhu N, Han L, Suo Q. Spectroscopic analysis and dissolution properties study of tosufloxacin tosylate/hydroxypropyl-\(\beta\)-cyclodextrin inclusion complex prepared by solution-enhanced dispersion with supercritical co 2. J Pharm Innov. 2019:1–14.
Gidwani B, Vyas A. A comprehensive review on cyclodextrin-based carriers for delivery of chemotherapeutic cytotoxic anticancer drugs. Biomed Res Int. 2015.
Kantner I, Erben RG. Long-term parenteral administration of 2-hydroxypropyl-\(\beta\)-cyclodextrin causes bone loss. Toxicol Pathol. 2012;40(5):742–50.
Gould S, Scott RC. 2-hydroxypropyl-\(\beta\)-cyclodextrin (hp-\(\beta\)-cd): a toxicology review. Food Chem Toxicol. 2005;43(10):1451–9.
Zhang Y, Cui L, Li F, Shi N, Li C, Yu X, Chen Y, Kong W. Design, fabrication and biomedical applications of zein-based nano/micro-carrier systems. Int J Pharm. 2016;513(1–2):191–210.
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB. Bioavailability of curcumin: problems and promises. Mol Pharm. 2007;4(6):807–18.
Yang Y, Anvari M, Pan CH, Chung D. Characterisation of interactions between fish gelatin and gum arabic in aqueous solutions. Food Chem. 2012;135(2):555–61.
Sathuvan M, Thangam R, Gajendiran M, Vivek R, Balasubramanian S, Nagaraj S, Gunasekaran P, Madhan B, Rengasamy R. \(\kappa\) \(\kappa\)-carrageenan: An effective drug carrier to deliver curcumin in cancer cells and to induce apoptosis. Carbohydr Polym. 2017;160:184–93.
Roy S, Rhim JW. Preparation of antimicrobial and antioxidant gelatin/curcumin composite films for active food packaging application. Colloids Surf B Biointerfaces. 2019:110761
Jantarat C, Sirathanarun P, Ratanapongsai S, Watcharakan P, Sunyapong S, Wadu A. Curcumin-hydroxypropyl-\(\beta\)-cyclodextrin inclusion complex preparation methods: effect of common solvent evaporation, freeze drying, and ph shift on solubility and stability of curcumin. Trop J Pharm Res. 2014;13(8):1215–23.
Yadav VR, Suresh S, Devi K, Yadav S. Effect of cyclodextrin complexation of curcumin on its solubility and antiangiogenic and anti-inflammatory activity in rat colitis model. Aaps Pharmscitech. 2009;10(3):752–62.
Mangolim CS, Moriwaki C, Nogueira AC, Sato F, Baesso ML, Neto AM, Matioli G. Curcumin-\(\beta\)-cyclodextrin inclusion complex: stability, solubility, characterisation by ft-ir, ft-raman, x-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem. 2014;153:361–70.
Yallapu MM, Jaggi M, Chauhan SC. \(\beta\)-cyclodextrin-curcumin self-assembly enhances curcumin delivery in prostate cancer cells. Colloids Surf B Biointerfaces. 2010;79(1):113–25.
Devi N, Deka C, Nath P, Kakati DK. Encapsulation of theophylline in gelatin a–pectin complex coacervates. In: Infectious Diseases and Nanomedicine III. Springer. 2018:63–74
Saikia C, Das MK, Ramteke A, Maji TK. Evaluation of folic acid tagged aminated starch/zno coated iron oxide nanoparticles as targeted curcumin delivery system. Carbohydr Polym. 2017;157:391–9.
Singh N, Thukral DK, Chawla S. Formulation and evaluation of pegylated gms based solid lipid nanoparticles. International Journal of Biotechnology and Biomedical Sciences. p-ISSN 2454-4582, e-ISSN 2454-7808, Volume 3, Issue 1; January-June, 2017 pp. 52-57 © Krishi Sanskriti Publications http://www.krishisanskriti.org
Carbinatto FM, de Castro AD, Evangelista RC, Cury BS. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices. Asian J Pharm Sci. 2014;9(1):27–34
Khatun B, Baishya P, Ramteke A, Maji T. Study of the complexation of structurally modified curcumin with hydroxypropyl beta cyclodextrin and its effect on anticancer activity. New J Chem. 2020.
Majumder M, Debnath S, Gajbhiye RL, Saikia R, Gogoi B, Samanta SK, Das DK, Biswas K, Jaisankar P, Mukhopadhyay R. Ricinus communis l. fruit extract inhibits migration/invasion, induces apoptosis in breast cancer cells and arrests tumor progression in vivo. Sci Rep. 2019;9(1):1–14
Yang X. Clonogenic assay to test cancer therapies. Bio-Protoc. 2012;2(10):1–3.
Jeng TW, Hendon R, Fraenkel-Conrat H. Search for relationships among the hemolytic, phospholipolytic, and neurotoxic activities of snake venoms. Proc Natl Acad Sci. 1978;75(2):600–4.
Doley R, Mukherjee AK. Purification and characterization of an anticoagulant phospholipase a2 from indian monocled cobra (Naja kaouthia) venom. Toxicon. 2003;41(1):81–91.
Gupta K, Barua S, Hazarika SN, Manhar AK, Nath D, Karak N, Namsa ND, Mukhopadhyay R, Kalia VC, Mandal M. Green silver nanoparticles: enhanced antimicrobial and antibiofilm activity with effects on dna replication and cell cytotoxicity. RSC Adv. 2014;4(95):52845–55.
Mohan PK, Sreelakshmi G, Muraleedharan C, Joseph R. Water soluble complexes of curcumin with cyclodextrins: Characterization by ft-raman spectroscopy. Vib Spectrosc. 2012;62:77–84.
Yao Y, Xie Y, Hong C, Li G, Shen H, Ji G. Development of a myricetin/hydroxypropyl-\(\beta\)-cyclodextrin inclusion complex: Preparation, characterization, and evaluation. Carbohydr Polym. 2014;110:329–37.
Esmaili SK, Ghanbarzadeh B, Ayaseh A, Pezeshki A, Hosseini M. Design, fabrication and characterization of pectin-coated gelatin nanoparticles as potential nano-carrier system. J Food Biochem. 2019;43(2):e12729.
Gómez-Mascaraque LG, Llavata-Cabrero B, Martínez-Sanz M, Fabra MJ, López-Rubio A. Self-assembled gelatin-\(\iota\)-carrageenan encapsulation structures for intestinal-targeted release applications. J Colloid Interface Sci. 2018;517:113–23.
Rachmawati H, Edityaningrum CA, Mauludin R. Molecular inclusion complex of curcumin-\(\beta\)-cyclodextrin nanoparticle to enhance curcumin skin permeability from hydrophilic matrix gel. Aaps Pharmscitech. 2013;14(4):1303–12.
Devi N, Kakati DK. Smart porous microparticles based on gelatin/sodium alginate polyelectrolyte complex. J Food Eng. 2013;117(2):193–204.
Moniha V, Alagar M, Selvasekarapandian S, Sundaresan B, Boopathi G. Conductive bio-polymer electrolyte iota-carrageenan with ammonium nitrate for application in electrochemical devices. J Non-Cryst Solids. 2018;481:424–34.
Sankalia MG, Mashru RC, Sankalia JM, Sutariya VB. Physicochemical characterization of papain entrapped in ionotropically cross-linked kappa-carrageenan gel beads for stability improvement using doehlert shell design. J Pharm Sci. 2006;95(9):1994–2013.
Sahraee S, Ghanbarzadeh B, Milani JM, Hamishehkar H. Development of gelatin bionanocomposite films containing chitin and zno nanoparticles. Food Bioprocess Technol. 2017;10(8):1441–53.
Devamani RHP, Deepa N, Gayathri J. Morphology and thermal studies of calcium carbonate nanoparticles. Int J Innov Sci Eng Technol. 2016;3(1):87–9.
Hedges A. Cyclodextrins: properties and applications. In: Starch, Elsevier. 2009:833–51.
Devi N, Maji TK. Genipin crosslinked microcapsules of gelatin a and \(\kappa\)-carrageenan polyelectrolyte complex for encapsulation of neem (Azadirachta indica a. juss.) seed oil. Polym Bull. 2010;65(4):347–62.
Kimura E, Aoki S, Kikuta E, Koike T. A macrocyclic zinc (ii) fluorophore as a detector of apoptosis. Proc Natl Acad Sci. 2003;100(7):3731–6.
Acknowledgements
The authors would like to thank Tezpur University for the necessary technical facilities and infrastructure to carry out the research work. The authors would like to acknowledge Dr. Rajendra Joshi, Founder & CEO at RI Instruments & Innovation INDIA for the instrumental facility of Raman Spectroscopy. Financial support in the form of Maulana Azad National Fellowship, UGC, Govt. of India is highly acknowledged by the author Bably Khatun.
Funding
No funding was received for conducting this study
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Consent for Experimentation
The authors have the consent from Tezpur University Ethical Committee (TUEC) Memo No. DoRD/TUEC/10-14/3086-A for the use of isolated lymphocytes for the experiment. Blood sample was given voluntarily by me (Bably Khatun) with the help of Institutional health centre.
Consent to Participate
The work has been done with the consent of all the participants
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
Khatun, B., Majumder, M., Mukhopadhyay, R. et al. Effect of Curcumin-Hydroxypropyl-\(\beta\)-Cyclodextrin Complex and the Complex Loaded Gelatin Carrageenan Microparticles on the Various Chemical and Biological Properties. J Pharm Innov 17, 806–820 (2022). https://doi.org/10.1007/s12247-021-09559-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12247-021-09559-0