Abstract
With excellent biological, physical and chemical properties of cellulose nanocrystals, a novel colon-targeted drug release system was created by conjugating of model drug (tosufloxacintosilate, TFLX) with maleic anhydride cellulose nanocrystals (MCNCs), in which l-leucine was used as a spacer molecule. The satisfactory drug loading of 29.14% as well as high encapsulation efficiency of 99.84% were obtained. The hydrodynamic diameters of MCNCs, drug (TFLX) and drug conjugates are 124, 491 and 520 nm, respectively, which demonstrates that MCNCs might adhere to the surface of drug tightly. The successful linking of l-leucine to MCNCs and amidation reaction between drug and A-MCNCs were confirmed by FTIR and XPS spectra. Moreover, the release behaviors of drug conjugates and fluorescent-labeled drug conjugates in simulated fluids were investigated by in vitro study and fluorescence detection. It is found that the drug conjugates could release about 72.55% of the drug loaded in the simulated colon fluid with enzyme lysozyme after 30 h, but no drug was detected in simulated gastric fluids with enzyme pepsin. The results illustrate that the model drug could be entrapped efficiently by MCNCs and have an excellent behavior for colon-targeted release. The paper reveals that cellulose nanocrystals can be considered potential carriers in colon specific drug delivery system.
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Agarwal T, Gautham Hari Narayana SN, Pal K, Pramanik K, Giri S, Banerjee I (2015) Calcium alginate-carboxymethyl cellulose beads for colon-targeted drug delivery. Int J Biol Macromol 75:409–417
Akhlaghi SP, Berry RC, Tam KC (2013) Surface modification of cellulose nanocrystal with chitosan oligosaccharide for drug delivery applications. Cellulose 20:1746–1747
Alila S, Ferraria AM, do Rego AMB, Boufi S (2009) Controlled surface modification of cellulose fibers by amino derivatives using N, N′-carbonyldiimidazole as activator. Carbohyd Polym 77:553–562
Amidon S, Brown JE, Dave VS (2015) Colon-targeted oral drug delivery systems: design trends and approaches. AAPS PharmSciTech 16(4):731–741
Barazzouk S, Daneault C (2012) Tryptophan-based peptides grafted onto oxidized nanocellulose. Cellulose 19:481–493
Basit AW (2005) Advances in colonic drug delivery. Drugs 65(14):1991–2007
Cai X, Yang L, Zhang L, Wu Q (2009) Synthesis and anaerobic biodegradation of indomethacin-conjugated cellulose ethers used for colon-specific drug delivery. Bioresour Technol 100:4164–4170
Charbe NB, McCarron PA, Lane ME, Tambuwala MM (2017) Application of three-dimensional printing for colon targeted drug delivery systems. Int J Pharm Investig 7(2):47–59
Cui F, Qian F, Zhao Z, Yin L, Tang C, Yin C (2009) Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles. Biomacromolecules 10:1253–1258
Deng F, Liu Y (2012) Study of the interaction between tosufloxacin tosylate and bovine serum albumin by multi-spectroscopic methods. J Lumin 132:443–448
Dong S, Cho HJ, Lee YW, Roman M (2014) Synthesis and cellular uptake of folic acid-conjugated cellulose nanocrystals for cancer targeting. Biomacromolecules 15(5):1560–1567
Edwards C (1997) Physiology of the colorectal barrier. Adv Drug Deliv Rev 28(2):173–190
Endes C, Mueller S, Kinnear C, Vanhecke D, Johan Foster E, Petri-Fink A, Weder C, Clift MJD, Rothen-Rutishauser B (2015) Fate of cellulose nanocrystal aerosols deposited on the lung cell surface in vitro. Biomacromolecules 16:1267–1275
Ewe K, Schwartz S, Petersen S, Press AG (1999) Inflammation does not decrease intraluminal pH in chronic inflammatory bowel disease. Dig Dis Sci 44(7):1434–1439
Galindo-Rodríguez SA, Allemann E, Fessi H, Doelker E (2005) Polymeric nanoparticles for oral delivery of drugs and vaccines: a critical evaluation of in vivo studies. Crit Rev Ther Drug Carrier Syst 22:419–463
Gazzaniga A, Iamartino P, Maffione G, Sangalli ME (1994) Oral delayed-release system for colonic specific delivery. Int J Pharm 108(1):77–83
Hanif Z, Ahmed FR, Shin SW, Kim Y, Um SH (2014) Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma. Colloids Surf B 119:162–165
Hou L, Fang J, Wang W, Xie Z, Dongac D, Zhang N (2017) Indocyanine green-functionalized bottle brushes of poly(2-oxazoline) on cellulose nanocrystals for photothermal cancer therapy. J Mater Chem B 5:3348–3354
Ibekwe VC, Fadda HM, McConnell EL, Khela MK, Evans DF, Basit AW (2008) Interplay between intestinal pH, transit time and feed status on the in vivo performance of pH responsive ileo-colonic release systems. Pharm Res 25(8):1828–1835
Kinget R, Kalala W, Vervoort L, Mooter GU (1998) Colonic drug targeting. J Drug Target 6(2):129–149
Kopečný J, Hajer J, Mrázek J (2004) Detection of cellulolytic bacteria from the human colon. Folia Microbiol 49(2):175–177
Koshani R, Madadlou A (2018) A viewpoint on the gastrointestinal fate of cellulose nanocrystals. Trends Food Sci Technol 71:268–273
Kumar S, Negi YS, Ghosh MK, Choure K (2015) Renewable biopolymer-based excipients for colon drug delivery system: an overview. J Pharm Sci Res 7(3):166–174
Lemarchand C, Gref R, Couvreur P (2004) Polysaccharide-decorated nanoparticles. Eur J Pharm Biopharm 58:327–341
Lin N, Dufresne A (2013) Supramolecular hydrogels from in Situ host–guest inclusion between chemically modified cellulose nanocrystals and cyclodextrin. Biomacromolecules 14:871–880
Lin N, Dufresne A (2014) Nanocellulose in biomedicine: current status and future prospect. Eur Polym J 59:302–325
Liu Y, Li K, Liu B, Feng S (2010) A strategy for precision engineering of nanoparticles of biodegradable copolymers for quantitative control of targeted drug delivery. Biomaterials 31:9145–9155
Luo H, Xiong G, Hu D, Ren K, Yao F, Zhu Y, Gao C, Wan Y (2013) Characterization of TEMPO-oxidized bacterial cellulose scaffolds for tissue engineering applications. Mater Chem Phys 143(1):373–379
Matuana LM, Balatinecz JJ, Sodhi RNS, Park CB (2001) Surface characterization of esterified cellulosic fibers by XPS and FTIR spectroscopy. Wood Sci Technol 35:191–201
McClements DJ, Li Y (2010) Structured emulsion-based delivery systems: controlling the digestion and release of lipophilic food components. Adv Coll Interface Sci 159:213–228
Naseef H, Samaro A, Qurt MS, Nakhleh H, Kadamani N, Moqadi R, Enaya M (2016) Formulation and evaluation of oral biphasic drug delivery system of Metronidazole using HPMC polymer. Int J Pharm Sci Invent 5:22–30
Olsson RT, Azizi Samir MAS, Salazar-Alvarez G, Belova L, Ström V, Berglund LA, Ikkala O, Nogués J, Gedde UW (2010) Making flexible magnetic aerogels and stiff magnetic nanopaper using cellulose nanofibrils as templates. Nat Nanotechnol 5:584–588
Oprea A, Profire L, Lupusoru CE, Ghiciuc CM, Ciolacu D, Vasile C (2012) Synthesis and characterization of some cellulose/chondroitin sulphate hydrogels and their evaluation as carriers for drug delivery. Carbohyd Polym 87:721–729
Owens DE III, Peppas NA (2006) Opsonization, biodistribution, and pharmacokinetics of polymeric nanoparticles. Int J Pharm 307:93–102
Pachuau L, Mazumder B (2013) Colonic drug delivery systems based on natural polysaccharides and their evaluation. Mini Rev Med Chem 13:1982–1991
Patel M, Shah T, Amin A (2007) Therapeutic opportunities in colon-specific drug-delivery systems. Crit Rev Ther Drug Carrier Syst 24:147–202
Philip AK, Philip B (2010) Colon targeted drug delivery systems: a review on primary and novel approaches. Oman Med J 25(2):79–87
Qing W, Wang Y, Wang Y, Zhao D, Liu X, Zhu J (2016) The modified nanocrystalline cellulose for hydrophobic drug delivery. Appl Surf Sci 366:404–409
Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5:37–42
Roman M (2015) Toxicity of cellulose nanocrystals: a review. Ind Biotechnol 11:25–33
Rosilo H, Mckee JR, Kontturi E, Koho T, Hytönen VP, Ikkala O, Kostiainen MA (2014) Cationic polymer brush-modified cellulose nanocrystals for high-affinity virus binding. Nanoscale 6:11871–11881
Rubinstein A (2000) Natural polysaccharides as targeting tools of drugs to the human colon. Drug Dev Res 50:435–439
Serra L, Domenechc J, Peppas NA (2006) Drug transport mechanisms and release kinetics from molecularly designed poly(acrylic acid-g-ethylene glycol) hydrogels. Biomaterials 27:5440–5451
Shah N, Shah T, Amin A (2011) Polysaccharides: a targeting strategy for colonic drug delivery. Expert Opin Drug Deliv 8(6):779–796
Sinha VR, Kumria R (2003) Microbially triggered drug delivery to the colon. Eur J Pharm Sci 18:3–18
Takayaa T, Niwaa K, Muraokaa M, Ogitaa I, Nagaia N, Yanoa R, Kimuraa G, Yoshikawaa Y, Yoshikawab H, Takadaa K (1998) Importance of dissolution process on systemic availability of drugs delivered by colon delivery system. J Control Release 50(1–3):111–122
Tang L, Huang B, Yang N, Li T, Lu Q, Lin W, Chen X (2013) Organic solvent-free and efficient manufacture of functionalized cellulose nanocrystals via one-pot tandem reactions. Green Chem 15:2369–2373
Tang L, Li T, Zhuang S, Lu Q, Li P, Huang B (2016) Synthesis of pH-sensitive fluorescein grafted cellulose nanocrystals with an amino acid spacer. ACS Sustain Chem Eng 4:4842–4849
Trache D, Hazwan Hussin M, Mohamad Haafiz MK, Thakur VK (2017) Recent progress in cellulose nanocrystals: sources and production. Nanoscale 9:1763–1786
Wang H, Roman M (2011) Formation and properties of chitosan-cellulose nanocrystal polyelectrolyte-macroion complexes for drug delivery applications. Biomacromolecules 12:1585–1593
Wang M, Xie Y, Zheng Q, Yao S (2009) A Novel, Potential microflora-activated carrier for a colon-specific drug delivery system and its characteristics. Ind Eng Chem Res 48:5276–5284
Wang K, Nune KC, Misra RDK (2016) The functional response of alginate-gelatin-nanocrystalline cellulose injectable hydrogels toward delivery of cells and bioactive molecules. Acta Biomater 36:143–151
Zubavichus Y, Zharnikov M, Shaporenko A, Fuchs O, Weinhardt L, Heske C, Umbach E, Denlinger JD, Grunze M (2004) Soft X-ray induced decomposition of phenylalanine and tyrosine: a comparative study. J Phys Chem A 108(20):4557–4565
Acknowledgments
We appreciate the generous financial support of Special Scientific Research Fund for Public Service Sectors of Forestry (Grant No. 201504603), the Natural Science Foundation of Fujian Province of China (Grant No. 2016J01088), and Chemicals and Science Foundation for Distinguished Young Scholars of Fujian Agricultural and Forestry University (Grant No. xjq201422) and National Natural Science Foundation of China (Grant No. 31370560).
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Tang, L., Lin, F., Li, T. et al. Design and synthesis of functionalized cellulose nanocrystals-based drug conjugates for colon-targeted drug delivery. Cellulose 25, 4525–4536 (2018). https://doi.org/10.1007/s10570-018-1904-2
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DOI: https://doi.org/10.1007/s10570-018-1904-2