Abstract
Interpenetrating polymer network (IPN) using chitosan and egg white cross linked with polyvinylpyrrolidone and polyethylene glycol was prepared by heat coagulation method. 5-Fluorouracil (5-FU) was chosen as a model drug which is effective for several cancer treatments. Eleven formulations were prepared by keeping chitosan concentration constant and varying the concentration of egg white and heating time. The prepared nanoparticles were characterized using FE-SEM, FT-IR, P-XRD and TG/DTG studies. FE-SEM analysis indicated that the IPN nanoparticles exhibit a uniform and compact dense morphology. FTIR spectroscopy confirmed the formation of interpenetrating network and the chemical stability of 5-FU after penetration into IPN nanoparticles. P-XRD results demonstrated that the drugs were distributed in amorphous state in the IPN nanoparticles. Particle size, poly-dispersity index and zeta potential were evaluated. The entrapment efficiency and in vitro drug release behavior of drug loaded IPN nanoparticles were also studied. Entrapment efficiency is high for F-3 formulation. The release rate is relatively higher at alkaline pH 7.4 as compared to acidic pH 1.2 and this feature is desirable from perspective of site specific drug delivery. Cell cytotoxicity was assessed using MTT assay into HT 29 cell line and found that 5-FU loaded IPN nanoparticles prolonged the cytotoxic effect on HT-29 colon cancer cell lines in comparison to free 5-FU. This work provides a promising delivery system for sustained release of 5-FU.
Similar content being viewed by others
References
Agnihotri SA, Aminabhavi TM (2006) Novel interpenetrating network chitosan poly(ethylene oxide-g-acrylamide) hydrogel microspheres for the controlled release of capecitabine. Int J Pharm 324:103–115
Ajji Z, Othman I, Rosiak JM (2005) Production of hydrogel wound dressings using gamma radiation. Nucl Instrum Methods Phys Res B 229:375–380
Allen TM (1994) The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drug Deliv Rev 13:285–309
Alonso D, Gimeno M, Olayo R, Vazquez-Torres H, Sepulveda-Sanchez JD, Shirai K (2009) Cross-linking chitosan into UV-irradiated cellulose fibers for the preparation of antimicrobial-finished textiles. Carbohydr Polym 77:536–543
Angadi SC, Manjeswar LS, Aminabhavi TM (2010) Interpenetrating polymer network blend microspheres of chitosan and hydroxethyl cellulose for controlled release of isoniazid. Int J Biol Macromol 47:171
Athawale Vilas D, Sachin SR (2002) New interpenetrating polymer networks based on uralkyd/poly(glycidyl-methacrylate). Eur Polym J 38:2033–2040
Bajpai AK, Shukla SK, Bhanu S, Kankane S (2008) Responsive polymers in controlled drug delivery. Prog Polym Sci 33:1088–1118
Banerjee S, Ray S, Maiti S, Sen KK, Bhattacharyya UK, Kaity S, Ghosh A (2010) Interpenetrating polymer network (IPN): a novel biomaterial. Int J Appl Pharm 2:28–34
Beranova M, Wasserbauer R, Vancurova D, Stifter M, Ocenaskova J, Mara M (1990) Effect of cytochrome-p-450 inhibition and stimulation on intensity of polyethylene degradation in microsomal fraction of mouse and rat livers. Biomaterials 11:521–524
Bian F, Jia L, Yu W, Liu M (2009) Self-assembled micelles of N-phthaloylchitosan-g-polyvinylpyrrolidone for drug delivery. Carbohydr Polym 76:454–459
Boyer C, Whittaker MR, Bulmus V, Liu J, Davis TP (2010) The design and utility of polymer-stabilized iron-oxide nanoparticles for nanomedicine applications. NPG Asia Mater 2:23–30
Cascone MG, Sim B, Downes S (1995) Blends of synthetic and natural polymers as drug delivery systems for growth hormone. Biomaterials 16:569–574
Chandra Sekhar E, Krishna Rao KSV, Ramesh Raju R (2011) Chitosan/guargum-g-acrylamide semi IPN microspheres for controlled release studies of 5-Fluorouracil. J Appl Pharm Sci 01(08):199–204
Chen M, Liu Y, Yang W, Li X, Liu L, Zhou Z et al (2011) Preparation and characterization of self-assembled nanoparticles of 6-O-cholesterol-modified chitosan for drug delivery. Carbohydr Polym 84:1244–1251
Chikh L, Delhorbe V, Fichet O (2011) (Semi-)Interpenetrating polymer networks as fuel cell membranes. J Membr Sci 368:1–17
Chilarski A, Szosland L, Krucinska I, Kiekens P, Blasinska A, Schoukens G et al (2007) Novel dressing materials accelerating wound healing made from dibutyrylchitin. Fibers Tex Eas Eur 15:77–81
Chilin C, Metters AT (2006) Hydrogels in controlled release formulations: network design and mathematical modelling. Adv Drug Deliv Rev 58:1379–1408
Das D, Das R, Ghosh P, Dhara S, Panda AB, Pal S (2013) Dextrin cross linked with poly(HEMA): a novel hydrogel for colon specific delivery of ornidazole. RSC Adv 3:25340–25350
Ding P, Huang K-L, Li G-Y, Lin Y-F (2007) Preparation and properties of modified chitosan as potential matrix materials for drug sustained-release beads. Int J Biol Macromol 41:125
Ekici S, Saraydin D (2007) Interpenetrating polymeric network hydrogels for potential gastrointestinal drug release. Polym Int 56:1371–1377
Ganguly K, Aminabhavi TM, Kulkarni AR (2011) Colon targeting of 5-fluorouracil using Polythelene glycol cross-linked chitosan microspheres enteric coated with cellulose acetate phthalate. Ind Eng Chem Res 50:11797–11807
Gupta PK, Hung CT, Perrier DG (1986) Albumin microspheres I: release characteristics of adriamycin. Int J Pharm 33:137–146
Kawai F (2002) Microbial degradation of polyethers. Appl Microbiol Biotechnol 58:30–38
Kohei K (1997) Biomedical polymers. Polymer 14:229
Kovacs-Nolan J, Phillips M, Mine Y (2005) Advances in the value of eggs and egg components for human health. J Agric Food Chem 53(22):8421–8431
Kumar M, Muzzarelli RAA, Muzzarelli C, Sashiwa H, Domb A (2004) Chitosan chemistry and pharmaceutical perspectives. Chem Rev 1014:6017–6084
Li XD, Zhang LW (2005) Egg science and technology. Chemical Industry Press, Beijing
Liang B, He ML, Chan CY, Chen YC, Li XP, Li Y et al (2009) The use of folate-PEG grafted- hybranched-PEI nonviral vector for the inhibition of glioma growth in the rat. Biomaterials 30:4014–4020
Macdonald JS (1999) Toxicity of 5-fluorouracil. Oncology 13(7):33–34
Mandal BB, Kapoor S, Kundu SC (2009) Silk fibroin/polyacrylamide semi-interpenetrating network hydrogels for controlled drug release. Biomaterials 30:2826–2836
Mehvar R (2000) Modulation of the pharmacokinetics and pharmacodynamics of proteins by polyethylene glycol conjugation. J Pharm Pharm Sci 3:125–136
Mine Y (2002) Recent advances in egg protein functionality in the food system. World’s Poult Sci J 58:31–39
Nakamura R, Sugiyama H, Sato Y (1978) Factors contributing to the heat-induced aggregation of ovalbumin. Agric Biol Chem 42:819–824
Nishimura S, Kohgo O, Kurita K, Kuzuhara H (1991) Chemospecific manipulations of a rigid polysaccharide synthesis of novel chitosan derivatives with excellent solubility in common organic solvents by regioselective chemical modifications. Macromolecules 24:4745
Ong SY, Wu J, Moochhala SM, Tan MH, Lu J (2008) Development of a chitosan based wound dressing with improved hemostatic and antimicrobial properties. Biomaterials 29:4323–4332
Ouchi T, Hagihara Y, Takahashi K, Takano Y, Igarashi I (1992) Synthesis and antitumor activity of poly(ethylen glycol)s linked to 5-fluorouracil via a urethane or urea bond. Drug Des Discov 9(1):93–105
Paul AM, David AW, Siobhaan MK (2000) Sustained release of 5-fluorouracil from polymeric nanoparticles. J Pharm Pharm 52:1451–1459
Rajan M, Raj V, Al-Arfaj Abdullah A, Murugan AM (2013) Hyaluronidase enzyme core-5- fluorouracil-loaded chitosan-PEG-gelatin polymer nanocomposites as targeted and controlled drug delivery vehicles. Int J Pharm 453:514–522
Rokhade AP, Agnihotri SA, Patil SA, Mallikarjuna NN, Kulkarni PV, Aminabhavi TM (2006) Semi-interpenetrating polymer network microspheres of gelatin and sodium carboxymethyl cellulose for controlled release of ketorolac tromethamine. Carbohydr Polym 65:243–252
Rokhade AP, Shelke NB, Patil SA, Aminabhavi TM (2007) Novel interpenetrating polymer network microspheres of chitosan and methylcellulose for controlled release of theophylline. Carbohydr Polym 69:678
Schutyser JAJ, Diren NL, Boonstra, Tjerk O, Arnhem NL (1990) Interpenetrating polymer network of an aliphatic polyol(allylcarbonate) and epoxy resin. http://www.freepatentsonline.com/4957981.html. US Patent 4957981
Steitz B, Hofmann H, Axmann Y, Petri-Fink A (2008) Optical properties of annealed Mn2+ doped ZnS nanoparticles. J Lumin 128:92–98
Sugino H, Nitoda T, Juneja LR (1997) General chemical composition of hen eggs. In: Yamamoto T, Juneja LR, Hatta H, Kim M (eds) Hen eggs their basic and applied science. CRC Press, New York, pp 13–24
Woodle MC, Lasic DD (1992) Sterically stabilized liposomes. Biochim Biophys Acta 1113:171–199
Zhang J-T, Huang S-W, Cheng S-X, Zhuo R-X (2004) Preparation and properties of Poly(N-isopropylacrylamide/Poly(N-isopropylacrylamide) interpenetrating polymer networks for drug delivery. Polym Chem 42:1249–1254
Acknowledgments
One of the authors (P. Priya) would like to acknowledge the DST-INSPIRE division for providing the INSPIRE fellowship (IF150169).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Priya, P., Raja, A. & Raj, V. Interpenetrating polymeric networks of chitosan and egg white with dual crosslinking agents polyethylene glycol/polyvinylpyrrolidone as a novel drug carrier. Cellulose 23, 699–712 (2016). https://doi.org/10.1007/s10570-015-0821-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10570-015-0821-x