Structural, thermal, mechanical, swelling, drug release, antibacterial and cytotoxic properties of P(HEA/IA)/PVP semi-IPN hydrogels
Graphical abstract
Introduction
Synthetic hydrogels have well definied structure which can be modified in order to achieve the desired properties. The convenient method to modify the properties of hydrogels is to prepare multi-component polymer materials. The technique of preparing semi-interpenetrating polymer networks, as multi-component materials, is frequently used in the design and synthesis of various hydrogels. Semi-IPN is a blend of two polymers where only one is crosslinked in the presence of a linear polymer. These networks, in most cases show physico-chemical properties that can remarkably differ from those of their macromolecular constituents. Due to the outstanding performances of such materials semi-IPNs have been applied in many areas including medicine and pharmacy (Das, 2013, Roland, 2013, Wang et al., 2011).
Poly(2-hydroxyethyl acrylate) (PHEA) is one of the commonly used polymers for the synthesis of hydrogels, due to its biocompatibility and high hydrophilicity. PHEA hydrogels found a lot of applications in pharmaceutical and biomedical fields. It can be used for biomaterials as coatings, intraocular lenses, tissue scaffolds and devices for controlled drug delivery. To improve mechanical stability or swelling properties of hydrogels based on PHEA, they can be combined with hydrophilic polymers into blends or semi IPNs (Baino, 2010, Sanna et al., 2012, Chen et al., 2007).
Poly(vinyl pyrrolidone) (PVP), water soluble synthetic polymer, is widely used in medical applications, such as a blood plasma extender, and a carrier for drug delivery. PVP has low toxicity and it is used in medical, food, cosmetics and as a film-forming agent. Because of its special molecular structure, PVP has many outstanding properties. PVP has satisfied biocompatibility and hydrophilic properties, which have been used for composite tissue engineering matrices. It is one of the most frequently used interpenetrating polymer because it can be expected to influence hydrogels morphological, swelling, and drug release characteristics (Abdelrazek et al., 2013, Chadha et al., 2006, Domingues et al., 2013, Erizal et al., 2013, Giri et al., 2011, Marsano et al., 2005, Naghdeali and Adimi, 2015, Tomar and Sharma, 2013, Wang and Wang, 2010, Wei et al., 2014, Yanpeng et al., 2006).
Itaconic acid (IA) can be produced from renewable sources by fermentation. IA is very hydrophilic and it expected to show good biocompatibility because of its natural source. Small amounts of IA render good pH sensitivity and increased degree of hydrogel swelling (Bera et al., 2015, Gils et al., 2011, Okabe et al., 2009, Petruccioli et al., 1999, Rashid et al., 2016, Sakthivel et al., 2014, Sariri and Jafarian, 2002, Sudarkodi et al., 2012).
In our work a series of semi-IPN polymeric networks, based on monomers of 2-hydroxyethyl acrylate (HEA) and itaconic acid (IA), with poly(N-vinylpyrrolidone) (PVP) as a interpenetrating agent (P(HEA/IA)/PVP), were synthesized by free radical copolymerization/crosslinking reaction. By introducing highly biocompatible and hydrophilic, chemically inert and electrically neutral PVP, in pH and temperature sensitive HEA/IA copolymer networks, it was expected to obtain excellent biocompatibility with living tissues. The mole fraction of itaconic acid varied in order to determine how the pH sensitivity induced by IA affects the characteristics of the samples. Morphological, thermal, mechanical and swelling properties were examined. The antibacterial activity and cell viability were also tested.
Section snippets
Materials
Monomers 2-hydroxyethyl acrylate (HEA, Aldrich), itaconic acid (IA, Fluka), and polyvinyl pirrolidone (PVP, Aldrich Mw 360000) were used for semi-IPN synthesis. Ethylene glycol dimethacrylate (EGDMA, Aldrich) was used as crosslinking agent, potassium persulfate (PPS, Fluka) as initiator, and N,N, N′,N′-tetramethylene diamine (TEMED, Aldrich) as activator. The polymerization was performed in a water/ethanol mixture. Buffers were prepared using hydrochloric acid (La Chema), potassium chloride
P(HEA/IA)/PVP semi-IPN
Semi-IPNs were obtained by a simultaneous method, where a single crosslinker which has no possibility of any interaction with the second polymer is used. HEA and IA monomers were polymerized simultaneously in the presence of PVP polymer, in such a way that the HEA/IA copolymer is crosslinked and intermingled with PVP linear polymer. TEMED is used as an activator in order to activate polymerization process and EGDMA is used as crosslinker in order to create three-dimensional polymeric network (
Conclusion
Semi-IPN hydrogels based on HEA and IA were synthesized by free radical polymerization with PVP as interpenetrating agent to be used as novel controlled drug release devices. The mole contents of IA varied and the PVP content was constant. The equilibrium swelling behaviors of P(HEA/IA)/PVP samples indicated the remarkable sensitivity to the external pH and temperature. Semi-IPN hydrogel’s properties and parameters (Tg, qe, kinetics—Fickian, non-Fickian, DL, and EE) showed trend with the
Acknowledgment
This work has been supported by the Ministry for Education, Science and Technological Development of the Republic of Serbia (Grants Nos. 172062 and 172026).
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