Lamellar, micro-phase separated blends of methyl cellulose and dendritic polyethylene glycol, POSS-PEG
Introduction
Polysaccharides, among which are cellulosics, are abundant, renewable, biodegradable and non-toxic polymers, which are chemically modified for use in food and pharmaceutical applications. Methyl cellulose (MC), Fig. 1 is a nonionic cellulose ether formed by alkali treatment of cellulose followed by reaction with methylchloride. It has the same linear chain structure as cellulose, namely that based on the β-1,4 glucoside linkage of d-glucose. While cellulose is hydrophilic and contains intra- and inter-molecular hydrogen bonds in the ordered, crystalline regions, the partial, random substitution of the primary and secondary hydroxyl groups with methyl groups to form MC disrupts the hydrogen bonding interactions. The reaction methods used to synthesize commercial MC result in an inhomogeneous distribution of methoxy groups, consisting of highly methyl substituted hydrophobic and less substituted hydrophilic regions (Arisz et al., 1995, Hirrien et al., 1998, Kato et al., 1978, Kundu and Kundu, 2001, Savage, 1957), so that the material can be considered a multiblock copolymer. The degree of substitution (DS) is defined as the (average) number of methoxy groups divided by the number of anhydroglucose units (AGU). As the degree of substitution increases, the intermolecular hydrogen bonding that prevents cellulose from dissolving in water (and most other solvents) decreases, increasing the solubility of the MC in water.
Thermoreversible gelation is known to occur in aqueous solutions of MC, in which hydrogels form at elevated temperature, i.e. MC has a lower critical solution temperature (LCST) (Heymann, 1935, Kato et al., 1978, Kundu and Kundu, 2001, Sarkar, 1979). Recently, this phenomenon has been explained as simultaneous gelation (determined rheometrically) and phase separation (determined by cloud point measurements) via a nucleation and growth mechanism, with the formation of a volume spanning network of ∼14–15 nm diameter fibrils (Lott, McAllister, Arvidson, Bates, & Lodge, 2013). The tendency to form fibrils was found to be an intrinsic property of the polymer backbone (Lott, McAllister, Wasbrough, et al., 2013), but the detailed structure of the fibrils (i.e. how water is bound) is not currently known. However, there is some evidence that hydrophobic association (Hirrien et al., 1998, Kato et al., 1978) may play a role, since most homogeneously substituted celluloses do not gel, and none do if the chain contains no trisubstituted units (Hirrien et al., 1998, Savage, 1957), i.e. ones in which the 2, 3 and 6 OH are all replaced by methyl groups (2, 3, 6 MC) (see Fig. 1). Neither 2 MC nor 3, 6 MC exhibited thermoreversible gelation in water (Nakagawa et al., 2012).
MC and POSS individually have found applications in pharmacy, medicine and food products. MC is used as a binder/thickener (Cellulose & Cellulose Derivatives, 1963), as a coating material for drug tablets, in controlled drug release, sometimes in combination with the water insoluble ethylcellulose (EC) (Technical Handbook, 2000), or water-soluble polymers such as chitosan (Chen et al., 1996, Rabea et al., 2003, Synytsya et al., 2011), polyvinyl alcohol (PVA) and polyethylene glycols (Kim et al., 2012, Sakellariou et al., 1987), and in hydrogel scaffolds (Chang and Zhang, 2011, Shoichet, 2010). Polyhedral oligomeric silsesquioxanes (POSS) nanocomposites have been investigated for use in medical device and tissue engineering applications (Kannan et al., 2005, Wu and Mather, 2009), partly due to their nontoxicity and cytocompatibility (Kannan et al., 2006a, Kannan et al., 2006b, Kannan et al., 2007, Kim et al., 2007, Punshon et al., 2005, Wang et al., 2014), and ability to modulate hydrolytic biodegradation (Gu et al., 2011, Knight et al., 2009, Lee et al., 2008) and thus drug release (Guo, Knight, Wu, & Mather, 2010). Polyethylene glycol (PEG), a nontoxic oligomer of polyethylene oxide (PEO), is available in many molecular weights, is water soluble, and is used in a wide range of biomedical applications due to its ability to resist protein adhesion (Hoare and Kohane, 2008, Tessmar and Gopferich, 2007). PEG units have been incorporated as copolymers in POSS based polyurethanes (Knight, Lee, Qin, & Mather, 2008) and used, for example, as antimicrobial nanofibrous hydrogels containing AgNO3 (Wu, Hou, Ren, & Mather, 2009), and with polylactide/caprolactones for drug release (Guo et al., 2010). POSS-PEGs, POSS functionalized with polyethylene glycols (PEGs) (Fig. 1) so that they have a dendritic structure, have also been used in biomaterial applications, such as in scaffolds for aveolar bone repair using chemically crosslinked hydrogel networks based on triblock copolymers of poly(lactide-b-ethylene glycol-b-lactide)diacrylates (Wang et al., 2011, Wang et al., 2014)
Blends of MC with other natural (Arvanitoyannis and Biliaderis, 1999, Liang et al., 2004, Martin et al., 2008, Pinotti et al., 2007, Synytsya et al., 2011) and synthetic polymers/oligomers (Bochek et al., 2014, Donhowe and Fennema, 1993a, Guru et al., 2012, Park et al., 2001a, Shin and Kondo, 1998) can result in new and enhanced properties and uses (Arvanitoyannis & Biliaderis, 1999). In this paper, a novel blend composed of POSS-PEG and MC has been investigated, prepared from aqueous solution at room temperature, where POSS-PEG, MC and their mixtures do not gel in dilute solution. MC and semicrystalline polyethylene oxide (PEO) have been previously investigated and found to be partially miscible (Bochek, Zabivalova, Lavrent’ev, Abalov, & Gofman, 2011), as the result of hydrogen bonding between the ether oxygens of PEO and the primary hydroxyls at the C6 position (Kondo, Sawatari, Manley, & Gray, 1994). MC blends with an amorphous (at room temperature) PEG structure have advantages over semi-crystalline PEO, such as the ability of PEGs to inhibit non-specific protein adsorption and their anti-fouling properties. Thus these blends can have useful biomedical applications, for which it is important to know their physical properties.
To this end, blends of POSS-PEG/MC were investigated over a wide range of blend compositions, from 80/20 to 0/100 POSS-PEG/MC (by weight). Results from differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction, scanning (SEM) and scanning transmission (STEM) electron microscopy, and dynamic mechanical analysis (DMA) show the formation of a lamellar morphology for pure MC that incorporates bundles of fibrils within the lamellar planes, with enhanced mechanical properties compared with MC formed at high temperature (in the gel phase), where this morphology does not develop. Addition of POSS-PEG results in a porous structure, with pore size increasing with increasing POSS-PEG content, in which the pore walls have a micro-phase separated morphology, and where large amounts of the liquid POSS-PEG (as the dominant phase) can be incorporated with the formation of a material with rubbery mechanical properties. We propose that this occurs as the result of interactions between the MC and POSS-PEG at the phase boundaries, so that the MC acts as cross-link sites.
Section snippets
Materials
Methyl cellulose (MC) (Aldrich, primary supplier DOW, METHOCEL A) had an average molecular weight of 86,000 g/mol, 27.5–31.5 wt% methoxy groups and a degree of substitution of 1.6–1.9 mol methoxy per mol anhydroglucose units (as specified by manufacturer). Polyethylene glycol POSS (product number PG1190), with a chemical formula (C2m+3H4m+7Om+1)n(SiO1.5)n and n = 8, 10, 12 and m ∼ 13.3 and MW = 5576.6 g/mol (for n = 8), was a gift from Hybrid Plastics (Hattiesburg, MS) and is a viscous liquid at room
Gel and film formation
Thermoreversible gelation (upon heating) of MC occurred (Heymann, 1935) as is typically observed for commercial MC with a similar DS (1.6) (Sekiguchi, Sawatari, & Kondo, 2003). POSS-PEG was soluble in water from 0 to 90 °C and did not form a gel in this temperature range, in contrast to PEO (Dormidontova, 2002, Kjellander and Florin, 1981), POSS-PEG macromers with acrylate termination (Wang et al., 2014), amphiphilic hyperbranched PEG star copolymer (Zhou, Yan, Dong, & Tian, 2007), and branched
Conclusions
MC by itself, when cast from aqueous solution and evaporated at room temperature (RT), forms a lamellar structure in which fibril aggregates are embedded. This material has mechanical properties 3x greater than when the water is evaporated at higher temperatures (e.g. >60 °C) where the MC exists in the gel phase. We suggest that the restrictions of the fibril spanning gel morphology prevent subsequent aggregation of the fibrils and formation of the lamellar structure. Addition of POSS-PEG to the
Acknowledgements
We gratefully acknowledge NSF DMR 1207221 for support of this work, and Steven Patrick DiLuzio for determination of the gel temperatures. The scanning electron imaging was performed in the CoE-NIC facility at Temple University, which is based on DoD DURIP Award N0014-12-1-0777 from the Office of Naval Research and is sponsored by the College of Engineering, Temple University.
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Current address: Heraeus Materials Technology, West Conshohocken, PA, United States.