Abstract
Temperature-responsive aerogels from hydroxypropyl methylcellulose (HPMC)-grafted N-isopropylacrylamide (NIPAM) were developed for the first time as a novel drug delivery system. The morphology and structure of temperature-responsive HPMC-NIPAM aerogels were characterized with scanning electron microscopy, Fourier-transform infrared, X-ray diffraction, and X-ray photoelectron spectroscopic analyses. Water-soluble 5-fluorouracil was used as a model drug to study drug loading and release. Drug release experiments demonstrated a sustained and controlled release behavior of the HPMC-NIPAM aerogels that were highly dependent on temperature. Meanwhile, the first-order kinetic model, Higuchi model, and Korsmyer–Peppas model were used to fit the sustained-release curve of drug-loaded aerogel revealing a sustained-release mechanism.
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References
Aung NN, Ngawhirunpat T, Rojanarata T, Patrojanasophon P, Opanasopit P, Pamornpathomkul B (2019) HPMC/PVP dissolving microneedles: a promising delivery platform to promote trans-epidermal delivery of alpha-arbutin for skin lightening. AAPS PharmSciTech 21:25–25. https://doi.org/10.1208/s12249-019-1599-1
Blanco E, Shen H, Ferrari M (2015) Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol 33:941. https://doi.org/10.1038/nbt.3330
Brannon-Peppas L (1990) Preparation and characterization of crosslinked hydrophilic networks ntudies in polymer. Science 8:45–66. https://doi.org/10.1016/B978-0-444-88654-5.50008-X
Ch Ü, Kutlu M, Atıcı OG (2015) Mannich reaction of polysaccharides: xylan functionalization in aqueous basic medium. Carbohyd Polym 127:19–27
Chen N, Wang H, Ling C, Vermerris W, Wang B, Tong Z (2019) Cellulose-based injectable hydrogel composite for pH-responsive and controllable drug delivery. Carbohyd Polym 225:115207. https://doi.org/10.1016/j.carbpol.2019.115207
Dash S, Murthy PN, Nath L, Chowdhury P (2015) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223
Esquivel-Castro TA, Ibarra-Alonso MC, Oliva J, Martinez-Luevanos A (2019) Porous aerogel and core/shell nanoparticles for controlled drug delivery: a review. Mater Sci Eng C-Mater Biol Appl 96:915–940. https://doi.org/10.1016/j.msec.2018.11.067
Fazil M, Baboota S, Sahni JK, Ameeduzzafar AJ (2015) Bisphosphonates: therapeutics potential and recent advances in drug delivery. Drug Delivery 22:1–9. https://doi.org/10.3109/10717544.2013.870259
Foppoli A et al (2019) In vitro and human pharmacoscintigraphic evaluation of an oral 5-ASA delivery system for colonic release. Int J Pharmaceutics 572:118723. https://doi.org/10.1016/j.ijpharm.2019.118723
García-González CA, Alnaief M, Smirnova I (2011) Polysaccharide-based aerogels—promising biodegradable carriers for drug delivery systems. Carbohyd Polym 86:1425–1438. https://doi.org/10.1016/j.carbpol.2011.06.066
Ge L, Li X, Zhang R, Yang T, Ye X, Li D, Mu C (2015) Development and characterization of dialdehyde xanthan gum crosslinked gelatin based edible films incorporated with amino-functionalized montmorillonite. Food Hydrocolloids 51:129–135. https://doi.org/10.1016/j.foodhyd.2015.04.029
George J et al (2014) Hybrid HPMC nanocomposites containing bacterial cellulose nanocrystals and silver nanoparticles. Carbohyd Polym 105:285–292. https://doi.org/10.1016/j.carbpol.2014.01.057
Ha-Lien Tran P, Wang T, Yang C, Tran TTD, Duan W (2020) Development of conjugate-by-conjugate structured nanoparticles for oral delivery of docetaxel. Mater Sci Eng C-Mater Biol Appl 107:110346–110346. https://doi.org/10.1016/j.msec.2019.110346
Hu YW et al (2015) Selective redox-responsive drug release in tumor cells mediated by chitosan based glycolipid-like nanocarrier. J Controlled Release 206:91–100. https://doi.org/10.1016/j.jconrel.2015.03.018
Huo WQ, Xie GC, Zhang WX, Wang W, Shan JY, Liu HC, Zhou XH (2016) Preparation of a novel chitosan-microcapsules/starch blend film and the study of its drug-release mechanism. Int J Biol Macromol 87:114–122. https://doi.org/10.1016/j.ijbiomac.2016.02.049
Kim AR, Lee SL, Park SN (2018) Properties and in vitro drug release of pH- and temperature-sensitive double cross-linked interpenetrating polymer network hydrogels based on hyaluronic acid/poly (N-isopropylacrylamide) for transdermal delivery of luteolin. Int J Biol Macromol 118:731–740. https://doi.org/10.1016/j.ijbiomac.2018.06.061
Kolakovic R, Peltonen L, Laukkanen A, Hirvonen J, Laaksonen T (2012) Nanofibrillar cellulose films for controlled drug delivery. Eur J Pharm Biopharm 82:308–315. https://doi.org/10.1016/j.ejpb.2012.06.011
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35
Li J, Wang YJ, Zhang L, Xu ZY, Dai HQ, Wu WB (2019) Nanocellulose/gelatin composite cryogels for controlled drug release. ACS Sustainable Chem Eng 7:6381–6389. https://doi.org/10.1021/acssuschemeng.9b00161
Li J, Xu ZY, Wu WB, Jing Y, Dai HQ, Fang GG (2018a) Nanocellulose/Poly(2-(dimethylamino) ethyl methacrylate) Interpenetrating polymer network hydrogels for removal of Pb(II) and Cu(II) ions. Colloids Surfaces A Physicochem Eng Aspects 538:474–480. https://doi.org/10.1016/j.colsurfa.2017.11.019
Li YL et al (2018b) Ester crosslinking enhanced hydrophilic cellulose nanofibrils aerogel. ACS Sustainable Chem Eng 6:11979–11988. https://doi.org/10.1021/acssuschemeng.8b02284
Liao J, Huang H (2019) Temperature/pH dual sensitive Hericium erinaceus residue carboxymethyl chitin/poly (N-isopropyl acrylamide) sequential IPN hydrogels. Cellulose. https://doi.org/10.1007/s10570-019-02837-8
Marques NDN, Balaban RDC, Halila S, Borsali R (2018) Synthesis and characterization of carboxymethylcellulose grafted with thermoresponsive side chains of high LCST: The high temperature and high salinity self-assembly dependence. Carbohyd Polym 184:108–117. https://doi.org/10.1016/j.carbpol.2017.12.053
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. https://doi.org/10.1007/s002260100097
Pan Y, Wang J, Cai P, Xiao H (2018) Dual-responsive IPN hydrogel based on sugarcane bagasse cellulose as drug carrier. Int J Biol Macromol 118:132–140. https://doi.org/10.1016/j.ijbiomac.2018.06.072
Plappert SF, Liebner FW, Konnerth J, Nedelec J-M (2019) Anisotropic nanocellulose gel-membranes for drug delivery: tailoring structure and interface by sequential periodate-chlorite oxidation. Carbohyd Polym 226:115306. https://doi.org/10.1016/j.carbpol.2019.115306
Ritger PL, Peppas NA (1987) A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Controlled Release 5:37–42. https://doi.org/10.1016/0168-3659(87)90035-6
Saini K, Prabhuraj RS, Bandyopadhyaya R (2020) Development of mesoporous silica nanoparticles of tunable pore diameter for superior Gemcitabine drug delivery in pancreatic cancer cells. J Nanosci Nanotechnol 20:3084–3096. https://doi.org/10.1166/jnn.2020.17381
Samal SK, Dash M, Dubruel P, Van Vlierberghe S (2014) Smart polymer hydrogels: properties, synthesis and applications. In: Smart polymers and their applications, pp 237–270. https://doi.org/10.1533/9780857097026.1.237
Shao L, Cao Y, Li Z, Hu W, Li S, Lu L (2018) Dual responsive aerogel made from thermo/pH sensitive graft copolymer alginate-g-P(NIPAM-co-NHMAM) for drug controlled release Int J Biol Macromol 114:1338–1344 https://doi.org/10.1016/j.ijbiomac.2018.03.166
Siepmann J, Peppas NA (2012) Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Delivery Rev 64:163–174. https://doi.org/10.1016/j.addr.2012.09.028
Smirnova I, Suttiruengwong S, Arlt W (2004) Feasibility study of hydrophilic and hydrophobic silica aerogels as drug delivery systems. J Non-Crystalline Solids 350:54–60. https://doi.org/10.1016/j.jnoncrysol.2004.06.031
Sun B, Zhang M, Shen J, He Z, Fatehi P, Ni Y (2019) Applications of Cellulose-based. Mater Sustained Drug Delivery Syst Curr Med Chem 26:2485–2501. https://doi.org/10.2174/0929867324666170705143308
Sun S, Wu P (2011) A one-step strategy for thermal- and pH-responsive graphene oxide interpenetrating polymer hydrogel networks. J Mater Chem 21:4095–4097. https://doi.org/10.1039/c1jm10276a
Valo H et al (2013) Drug release from nanoparticles embedded in four different nanofibrillar cellulose aerogels. Eur J Pharm Sci 50:69–77. https://doi.org/10.1016/j.ejps.2013.02.023
Vasile C, Bumbu GG, Petronela Dumitriu R, Staikos G (2004) Comparative study of the behavior of carboxymethyl cellulose-g-poly(N-isopropylacrylamide) copolymers and their equivalent physical blends. Eur Polymer J 40:1209–1215. https://doi.org/10.1016/j.eurpolymj.2003.12.023
Vazhayal L, Talasila S, Azeez PMA, Solaiappan A (2014) Mesochanneled hierarchically porous aluminosiloxane aerogel microspheres as a stable support for pH-responsive controlled drug release. ACS Appl Mater Interfaces 6:15564–15574. https://doi.org/10.1021/am50422z
Veerabadran NG, Price RR, Lvov YMJN (2007) Clay nanotubes for encapsulation and sustained release of drugs. NANO 2:115–120. https://doi.org/10.1142/S1793292007000441
Veres P, Kéri M, Bányai I, Lázár I, Fábián I, Domingo C, Kalmár J (2017) Mechanism of drug release from silica-gelatin aerogel—relationship between matrix structure and release kinetics. Colloids Surfaces B Biointerfaces 152:229–237. https://doi.org/10.1016/j.colsurfb.2017.01.019
Wang DC, Yu HY, Fan X, Gu J, Ye S, Yao J, Ni QQ (2018) High aspect ratio carboxylated cellulose nanofibers crosslinked to robust aerogels for superabsorption−flocculants: paving way from nano-scale to macro-scale. ACS Appl Mater Interfaces 10:20755–20766. https://doi.org/10.1021/acsami.8b04211
Wang P, Li Y, Zhang C, Feng F, Zhang H (2020) Sequential electrospinning of multilayer ethylcellulose/gelatin/ethylcellulose nanofibrous film for sustained release of curcumin Food Chem 308:125599 https://doi.org/10.1016/j.foodchem.2019.125599
Wang T, Chen L, Shen T, Wu D (2016) Preparation and properties of a novel thermo-sensitive hydrogel based on chitosan/hydroxypropyl methylcellulose/glycerol. Int J Biol Macromol 93:775–782. https://doi.org/10.1016/j.ijbiomac.2016.09.038
Wang Y, Su Y, Wang W, Fang Y, Riffat SB, Jiang F (2019) The advances of polysaccharide-based aerogels: Preparation and potential application. Carbohyd Polym 226:115242. https://doi.org/10.1016/j.carbpol.2019.115242
Wu Z, Hong Y (2019) Combination of the silver–ethylene interaction and 3D printing to develop antibacterial superporous hydrogels for wound management. ACS Appl Mater Interfaces 11:33734–33747. https://doi.org/10.1021/acsami.9b14090
Zhang XF, Wang YR, Zhao JQ, Xiao MJ, Zhang W, Lu CH (2016) Mechanically strong and thermally responsive cellulose nanofibers/poly(N-isopropylacrylamide) composite aerogels. ACS Sustainable Chem Eng 4:4321–4327. https://doi.org/10.1021/acssuschemeng.6b00814
Zhao J, Lu C, He X, Zhang X, Zhang W, Zhang X (2015a) Polyethyleneimine-grafted cellulose nanofibril aerogels as versatile vehicles for drug delivery. ACS Appl Mater Interfaces 7:2607–2615. https://doi.org/10.1021/am507601m
Zhao J, Lu C, Xu H, Zhang X, Wei Z, Zhang X (2015b) Polyethylenimine-grafted cellulose nanofibril aerogels as versatile vehicles for drug delivery. ACS Appl Mater Interfaces 7:2607
Acknowledgments
The authors are grateful for the National Natural Science Foundation of China (Grant Nos. 31971605), International Joint Research Center for biomass chemistry and materials, Shaanxi international science and technology cooperation base (2018GHJD-19), the Shandong Key R&D Program (No. 2019JZZY010407 and 2019JZZY010304), Key scientific research plan (Key Laboratory) of Shaanxi Provincial Education Department (No.17JS016). The Project also was supported by the Foundation (No. KF201814) of Key Laboratory of Pulp and Paper Science and Technology of Ministry of Education/Shandong Province of China. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.
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Liu, Z., Zhang, S., He, B. et al. Temperature-responsive hydroxypropyl methylcellulose-N-isopropylacrylamide aerogels for drug delivery systems. Cellulose 27, 9493–9504 (2020). https://doi.org/10.1007/s10570-020-03426-w
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DOI: https://doi.org/10.1007/s10570-020-03426-w