FABRICATION OF DRUG DELIVERY SYSTEM FOR CONTROLLED RELEASE OF CURCUMIN, INTERCALATED WITH MAGNETITE NANOPARTICLES THROUGH SODIUM ALGINATE/POLYVINYLPYRROLIDONE-CO-VINYL ACETATE SEMI IPN MICROBEADS
DOI:
https://doi.org/10.22159/ijap.2020v12i5.37761Keywords:
Sodium alginate, Poly(vinylpyrrolidone)-co-vinyl acetate, Magnetite nanoparticles, Curcumin, MicrobeadsAbstract
Objective: The aim of the present work is to fabricate curcumin (CUR) encapsulated microbeads in the polymer matrix of sodium alginate (SA)/poly(vinylpyrrolidone)-co-vinyl acetate (PVP-co-VAc) intercalated with magnetite nanoparticles (MNPs) using glutaraldehyde (GA)/calcium chloride CaCl2 as the crosslinker.
Methods: Magnetite nanoparticles (MNPs) were synthesized by a modified co-precipitation method. Curcumin encapsulated SA/PVP-co-VAc microbeads, intercalated with MNPs were prepared by simple ionotropic gelation technique. The formation of microbeads and uniform distribution of curcumin were characterized using spectroscopic methods. In addition, swelling and drug release kinetic studies of the microbeads were performed in simulated intestinal fluid (pH 7.4) and simulated gastric fluid (pH 1.2) at 37 °C.
Results: Microbeads formation was confirmed by Fourier Transform Infrared (FTIR). Differential Scanning Calorimetry (DSC) studies reveal that the peak at 181 °C of CUR was not observed in CUR loaded microbeads, which confirms that CUR was encapsulated at the molecular level in the polymer matrix. The X-Ray diffraction (X-RD) diffractograms of CUR shows 2Ө peaks between 12-28 °, which indicated the crystalline nature of CUR, these peaks are not found in CUR loaded microbeads, suggesting that the drug has been molecularly dispersed in the polymer matrix. The X-RD 2Ө peaks of MNPs are observed in the MNPs loaded microbeads, which confirms that MNPs are successfully loaded in the microbeads. The swelling studies and in vitro release studies were performed at pH 1.2 and 7.4. The results reveal that at pH 7.4 highest swelling and release was observed, which confirms that the developed microbeads are pH sensitive and are suitable for intestinal drug delivery. The drug release kinetics fit into the Korsmeyer-Peppas equation, indicating non-Fickian diffusion.
Conclusion: The results concluded that the present system as dependent on pH of the test medium and hence suggest suitability for intestinal drug delivery.
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References
Nokhodchi A, Raja S, Patel P, Asare Addo K. The role of oral controlled release matrix tablets in drug delivery systems. BioImpacts: BI 2012;2:175-87.
Işıklan N, İnal M, Yigitoglu M. Synthesis and characterization of poly(N-vinyl-2-pyrrolidone) grafted sodium alginate hydrogel beads for the controlled release of indomethacin. J Appl Polym Sci 2008;110:481-93.
Pandey SP, Shukla T, Dhote VK, K Mishra D, Maheshwari R, Tekade RK. Chapter 4-use of polymers in controlled release of active agents. In: Tekade RK. (editor). Basic fundamental of drug delivery: Academic Press; 2019. p. 113-72.
Reddy OS, Subha MCS, Jithendra T, Madhavi C, Chowdoji Rao K. Fabrication of Gelatin/Karaya gum blend microspheres for the controlled release of distigmine bromide. J Drug Delivery Ther 2019;9:1-11.
Al-Kahtani AA, Sherigara BS. Semi-interpenetrating network of acrylamide-grafted-sodium alginate microspheres for controlled release of diclofenac sodium, preparation and characterization. Colloids Surf B Biointerfaces 2014;115:132-8.
Krishna Rao KSV, Kiran Kumar ABV, Madhusudhan Rao K, Subha MCS, Lee YI. Semi-IPN hydrogels based on Poly(vinyl alcohol) for controlled release studies of chemotherapeutic agentand their swelling characteristics. Polym Bull 2008;61:81-90.
Reddy OS, Subha MCS, Jithendra T, Madhavi C, Rao KC, Mallikarjuna B. Sodium alginate/gelatin microbeads-intercalated with kaolin nanoclay for emerging drug delivery in wilson’s disease. Int J Appl Pharm 2019;11:71-80.
Reddy OS, Subha MCS, Jithendra T, Madhavi C, Rao KC. Fabrication and characterization of smart karaya gum/sodium alginate semi-IPN microbeads for controlled release of D-penicillamine drug. Polym Polym Compos 2020;29:1–13.
Samanta HS, Ray SK. Synthesis, characterization, swelling and drug release behavior of semi-interpenetrating network hydrogels of sodium alginate and polyacrylamide. Carbohydr Polym 2014;99:666-78.
Shi G, Ding Y, Zhang X, Wu L, He F, Ni C. Drug release behavior of poly (lactic-glycolic acid) grafting from sodium alginate (ALG-g-PLGA) prepared by direct polycondensation. J Biomater Sci Polymer Edition 2015;26:1152-62.
Pina MF, Zhao M, Pinto JF, Sousa JJ, Craig DQM. The influence of physical drug state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: a case study using olanzapine. J Pharm Sci 2014;103:1214-23.
Bailly N, Thomas M, Klumperman B. Poly(N-vinylpyrrolidone)-block-poly(vinyl acetate) as a drug delivery vehicle for hydrophobic drugs. Biomacromolecules 2012;13:4109-17.
Savita B, Anirban M. Systemic delivery of curcumin: 21st century solutions for an ancient conundrum. Curr Drug Discovery Technol 2009;6:192-9.
Srimal RC, Dhawan BN. Pharmacology of diferuloylmethane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 1973;25:447-52.
Kumar A, Singh M, Singh PP, Singh SK, Raj P, Pandey KD. Antioxidant efficacy and curcumin content of turmeric (Curcuma-Longa L.) flower. Int J Curr Pharm Res 2016;8:112-4.
Kim MK, Choi GJ, Lee HS. Fungicidal property of Curcuma longa L. rhizome-derived curcumin against phytopathogenic fungi in a greenhouse. J Agric Food Chem 2003;51:1578-81.
Deodhar Sd Fau-Sethi R, Sethi R Fau-Srimal RC, Srimal RC. Preliminary study on antirheumatic activity of curcumin (diferuloylmethane). Indian J Med Res 1980;71:632-4.
Reddy OS, Subha MCS, Jithendra T, Madhavi C, Chowdoji Rao K. Emerging novel drug delivery system for control release of curcumin through sodium alginate/poly(ethylene glycol) semi IPN microbeads-intercalated with kaolin nanoclay. J Drug Delivery Ther 2019;9:324-33.
Lachowicz D, Karabasz A, Bzowska M, Szuwarzynski M, Karewicz A, Nowakowska M. Blood-compatible, stable micelles of sodium alginate–Curcumin bioconjugate for anti-cancer applications. Eur Polym J 2019;113:208-19.
Lu AH, Salabas EL, Schüth F. Magnetic nanoparticles: synthesis, protection, functionalization, and application. Angew Chem Int Ed 2007;46:1222-44.
Ito A, Shinkai M, Honda H, Kobayashi T. Medical application of functionalized magnetic nanoparticles. J Biosci Bioeng 2005;100:1-11.
Saiyed ZM, Telang SD, Ramchand CN. Application of magnetic techniques in the field of drug discovery and biomedicine. Biomagn Res Technol 2003;1:1-8.
Namdeo M, Saxena S Fau Tankhiwale R, Tankhiwale R Fau Bajpai M, Bajpai M Fau Mohan YM, Mohan Ym Fau Bajpai SK, Bajpai SK. Magnetic nanoparticles for drug delivery applications. J Nanosci Nanotechnol 2008;8:3247-71.
Cole AJ, Yang VC, David AE. Cancer theranostics: the rise of targeted magnetic nanoparticles. Trends Biotechnol 2011;29:323-32.
Maeda H. Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug Chem 2010;21:797-802.
Pollert E, Veverka P, Veverka M, Kaman O, Zaveta K, Vasseur S, et al. Search of new core materials for magnetic fluid hyperthermia: preliminary chemical and physical issues. Progress Solid State Chem 2009;37:1-14.
Veiseh O, Gunn JW, Zhang M. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging. Adv Drug Delivery Rev 2010;62:284-304.
Zhang L, Yu F, Cole AJ, Chertok B, David AE, Wang J, et al. Gum arabic-coated magnetic nanoparticles for potential application in simultaneous magnetic targeting and tumor imaging. AAPS J 2009;11:693-9.
Johannsen M, Gneveckow U, Eckelt L, Feussner A, Waldofner N, Scholz R, et al. Clinical hyperthermia of prostate cancer using magnetic nanoparticles: presentation of a new interstitial technique. Int J Hyperthermia 2005;21:637-47.
Wilhelm C, Fortin JP Fau-Gazeau F, Gazeau F. Tumour cell toxicity of intracellular hyperthermia mediated by magnetic nanoparticles. J Nanosci Nanotechnol 2007;7:2933-7.
Sun C, Lee JSH, Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Delivery Rev 2008;60:1252-65.
Rajput S, Pittman CU, Mohan D. Magnetic magnetite (Fe3O4) nanoparticle synthesis and applications for lead (Pb2+) and chromium (Cr6+) removal from water. J Colloid Interface Sci 2016;468:334-46.
Madhusudana Rao K, Krishna Rao KSV, Ramanjaneyulu G, Ha CS. Curcumin encapsulated pH sensitive gelatin-based interpenetrating polymeric network nanogels for anti-cancer drug delivery. Int J Pharm 2015;478:788-95.
Lori N, Eydokia P, Vassilis Z, Anna P, Eleana H, Christos NP. Magnetic nanoparticles in medical diagnostic applications: synthesis, characterization and proteins conjugation. Curr Nanosci 2016;12:455-68.
Zhu HY, Jiang R, Xiao L, Li W. A novel magnetically separable γ-Fe2O3/crosslinked chitosan adsorbent: preparation, characterization and adsorption application for removal of hazardous azo dye. J Hazard Mater 2010;179:251-7.
Banerjee SS, Chen DH. Fast removal of copper ions by gum arabic modified magnetic nano-adsorbent. J Hazard Mater 2007;147:792-9.
Eswaramma S, Rao KSVK. Synthesis of dual responsive carbohydrate polymer-based IPN microbeads for controlled release of anti-HIV drug. Carbohydr Polym 2017;156:125-34.
Madhusudana Rao K, Mallikarjuna B, Krishna Rao KSV, Prabhakar MN, Chowdoji Rao K, Subha MCS. Preparation and characterization of pH sensitive poly(vinyl alcohol)/sodium carboxymethyl cellulose IPN microspheres for in vitro release studies of an anti-cancer drug. Polym Bull 2012;68:1905-19.
Madhavi C, Babu PK, Maruthi Y, Parandhama A, Reddy OS, Rao KC, et al. Sodium alginate-locust bean gum IPN hydrogel beads for the controlled delivery of the nimesulide-anti-inflammatory drug. Int J Pharm 2017;9:245-52.