Polymers sensitive to stimuli
One large group of macromolecular compounds is the so-called smart polymers or stimuli-sensitive polymers. These polymers are sensitive to physical stimuli, exhibiting changes in their physicochemical properties as a reaction to small changes in their surrounding environment, e.g., temperature, pH, ultrasounds, light, electric fields, and mechanical stress. They are also sensitive to chemical stimuli (e.g. pH, ionic strength) and biological stimuli (e.g., the presence of substances including, i.a., enzymes and biomolecules) (Almeida et al., 2012; Kim et al., 2009; Qiu and Park, 2012). The ability of polymers to produce fast microscopic changes in their structure in response to stimuli is rendered through changes to their shape, surface properties and solubility, or through sol–gel phase transition, which is employed in constructing drug carriers sensitive to stimuli (Jeong and Gutowska, 2002). The signal may be created artificially by “external” sources or may result from changes in the “internal environment”, e.g. accompanying certain pathophysiological states. Many monomers may be characterized by sensitivity to certain stimuli; however, every monomer can create homopolymers that are sensitive to a specific signal, or copolymers that react to many stimuli (Kim et al., 2009). The EZ Cap Reagent GG of macromolecular compounds constituents and methods of their synthesis enable polymers to be modified and the creation of carriers sensitive to specified stimuli in a narrow scope of changes. Consequently, these intelligent polymers can be used to construct more precise and programmed drug delivery systems. The stimuli cause a reaction by changing the molecular interactions between the polymer and solvent or between polymer’s chains. Variations of these behaviours may include changes in the polymer’s solubility, hydrophilic/hydrophobic balance and conformation. Tables 1 and 2 show the examples of polymers sensitive to specified stimuli and the possibilities of employing these compounds in drug delivery systems, respectively.
Thermosensitive polymers are macromolecular compounds which exhibit temperature dependence of the sol–gel transition in water solutions. The transition in these systems from a viscous liquid into elastic form takes place when exposed to a lower critical solution temperature (LCST) as a result of a fast viscosity increase (Jeong et al., 2002). In solutions of thermosensitive macromolecular compounds, the increase of temperature to LCST causes an entropy increase (ΔS>ΔH) and a decrease in the free energy of binding (ΔG<0), which facilitates the replacement of the interactions between polymer chain and solvent molecules by intra- and interchain hydrophobic interactions and intra- and intermolecular hydrogen bonds (Bromberg and Ron, 1998). Temperature-sensitive polymers can be divided into four groups: polymers whose phase transition is based on LCST, polymers whose sol–gel transition is connected with the existence of amphiphilic balance, biopolymers and artificial polypeptides (Aguilar et al., 2007). The thermosensitive synthetic polymers characterized by phase transition in LCST include poly(N-isopropylacrylamide) (PNIPAAm), poly(N-vinyl isobutyl amid), poly(vinyl methyl ether), poly(N-vinylcaprolactam) (PVCL) and poly(dimethylamino ethyl methacrylate). The amphiphilic macromolecular compounds include mostly three-block copolymers built of polyoxyethylene and polyoxypropylene (PEO-PPO-PEO) and copolymers created as a result of replacing the PPO part in macromolecule structure with other blocks, i.e., poly(1,2-oxybutylene) (PBO), poly(l-lactic acid) (PLLA) or poly(lactide-co-glycolate) (PLGA) (Schmaljohann, 2006). Polysaccharides of thermosensitive properties are cellulose derivatives: ethylcellulose, hydroxyethyl cellulose (HEC) and ethyl hydroxyethyl cellulose (EHC), natural polysaccharides, e.g. agarose, amylose, amylopectin, carrageenan, gellan and its derivative, benzyl ester, creating in water solutions a double spiral structure stabilized by hydrogen bonds. Artificial polypeptides, e.g. elastin-like polymer (ELP) or silk-elastin-like block copolymers (SELPs), are polymers that dissolve in water below the phase transition temperature, forming a gel after it is exceeded as a result of desolvation and aggregation of the polymer’s subunits (Aguilar et al., 2007; Chilkoti et al., 2002).
Polymers sensitive to stimuli