PHYSICAL CHEMISTRY BEHAVIOUR OF STIMULI-SENSITIVE POLYMERS BASED ON VINYL ETHERS

3.1. Swelling behaviour of pH-sensitive co-polymers VAE-AA

The behaviour of co-polymer VAE-AA contained both ionic pH-sensitive carboxylic groups and hydrophobic VAE units has been studied in wide interval of pH medium.

Polymeric networks based on co-polymers VAE-AA characterized by pH-induced collapse (the equilibrium swelling degree of hydrogels abruptly decreases at narrow range of pH) (fig. 5).

FIG. 5. The dependence of swelling degree D on ɪɇ of surrounding solution for VBE-AA (a) and VIBE-AA (b) hydrogels. (a) P=0,01; [ȼȻɗ]:[ȺɄ], ɦɨɥ.%: 1–10,9:89, 1; 2–17,5:82,5; 3–28,2:71, 8;

(b) P=0,05; [ȼɢȻɗ]:[ȺɄ], ɦɨɥ.%: 1–9,8:90,2; 2–15, 1:84,9; 3–27,7:72,3.

The value of pH transition for VBE-AA hydrogels is located in alkaline area and practically independent on their composition. An increase of VBE content in cross-linked co-polymer is accompanied only by a decrease of transition amplitude. In contrast to VBE-AA, the pH of transition of VIBE-AA hydrogels is located in acidic area and an increase of VIBE content in co-polymers shifts the transition pH to the higher values. The observed different behaviour of networks is caused with more intensive hydrophobic interactions between normal structure butyl radicals than isomeric one. The additional ionization of carboxylic groups is required to overcome the hydrophobic interactions in VBE-AA, therefore the transition of these gels occured in alkaline pH region. The changing of pH from neutral to more acidic region depresses the ionization of carboxylic groups and decreases the electrostatic repulsion of macrochains for novel synthesized anionic networks. Besides an increase of ionic strength of the solutions shifts the pH transition of hydrogels of co-polymers VIBE-AA to the higher values region and decreases the collapse amplitude.

3.2. The swelling behaviour of thermo-sensitive co-polymers

Aqueous solutions of VEEG-VBE and VEEG-VIBE behave lower critical solution temperature (LCST). The value of LCST depends on co-polymer composition. An increasing of VBE content in co-polymer decreases the LCST value due to the strengthening of hydrophobic interactions. The values of critical temperature are lower for co-polymers enriched by hydrophobic components. Besides, for VEEG-VBE co-polymer characterized by lower values of LCST in comparison with VEEG-VIBE co-polymers. The reason of that is that alkyl substitutes with normal structure are more inclined to hydrophobic interactions, than isomeric substitutes. Moreover, the values of LCST can be decreased by low molecular weight salt addition because of salt-off effect.

Thermo-induced swelling behaviour of VEEG-VAE co-polymer network has been investigated via determination of swelling ratio V/V0 where V is swollen gel volume at goven temperature, V0 is synthesized hydrogel volume. The influence of the temperature has been investigated for polymer network with various compositions, but the similar cross-linking parameters (j). The temperature of transition from swollen state to collapsed one is reduced at increasing of containing of hydrophobic components in polymeric network and some abrupt of collapse i.e. temperature interval of transition is became more narrow (fig. 6). For temperature induced collapse of VEEG-VIBE co-polymers hydrogels with higher D values than that for VEEG-VBE networks the higher amplitudes of transition are shown.

FIG. 6. The swelling behaviour of VEEG-VBE (a) and VEEG-VIBE (b) co-polymers depending on temperature. [VEEG]:[VBE], mol%: 1–93.2:6.8; 2–84.1:15.9; 3–77.9:22.1; 1–D=72,3; j=2,6; 2–

D=40,1; j=2,6; 3–D=28,7; j=2,6; [VEEG]:[VIBE], mol%:1–93,4:6,6; 2–83,5:16,5; 3–77,1:22,9; 1–

D=77,2; j=2,6; 2–D=66,3; j=2,4; 3–D=56.8; j=2,4.

The cross-linking density of VEEG-VBE and VEEG-VIBE co-polymers hydrogels of same composition almost does not influence the temperature interval of transition, but it reduces the amplitude significantly.

With low weight salt addition the VEEG-VBE co-polymer hydrogel transition from swollen to collapsed state was observed at lower temperatures, and contraction amplitude became sharper. This effect is less noticeable for VEEG-VIBE co-polymer: collapse amplitude and transition temperature are reduced, but abrupt change is not observed. The character of temperature-induced collapse depends on the low weight salt cation and anion nature. It has been found that when transition temperature is decreased, the amplitude and discontinuity degree are amplified at Li⁺<Na⁺<K⁺ cations line, and I^-<Br^-<Cl^- anions line. It is necessary to note that anion nature change is accompanied by stronger effects compared with cation nature. It is in accordance with to the data/14/.

Therefore it is possible to affect on parameters of temperature induced collapse by variation of hydrophilic-hydrophobic balance of VEEG-VAB neutral network macrochains, their cross-linking density, ionic strength and low weight salt nature in the environmental medium.

3.3. Stimuli-sensitive behaviour of hybrid hydrogels

The practical application of stimuli-responsive systems frequently requires the possibility to control the parameters of hydrogels by simultaneous varying of both pH and temperature. Especially it is important for bio-medical application of polymers because many pathologies in organism are accompanied by simultaneous changes of pH and temperature.

Novel pH-dependent thermo-sensitive hydrogels, i.e. the polymeric networks with simultaneous sensitivity in respect to pH and temperature, were synthesized by co-polymerization of VEEG, VBE and AA with DVEDEG as a cross agent.

At the study of the swelling behaviour of three components of cross-linked co-polymers, the significant differences from binary systems VEEG-VBE and VBE-AA were found (fig. 7).

At the increasing of the temperature, in dependence on cross-linked co-polymers compositions three types of curves were observed. The monotonous swelling (curve 1), the swelling and following collapse (curve 3) and more complicated dependence, including swelling, collapse and the following repeated swelling (curve 2) were revealed.

FIG. 7. The dependence of VEEG-VBE-AA hydrogel swelling ratio on the temperature. [ȺA]=17,3 mol%; [ɋȺ]=5,0 mol%; [VEEG]:[VBE], mol%; 1–63,2:14,5; 2–57,6:20,1; 3–52,7:25,0.

The dependencies described by curves 1 and curve 3, are usual for thermo-sensitive hydrogels containing some ionogenous groups. The extremal dependences of swelling ratio of the VEEG-VBE-AA hydrogels with the increasing of the temperature qualitatively can be explained as a result of competitive influence of two factors. First is the increasing of hydrophobic interaction with the temperature that leads to the network contraction. Second is increasing of thermal motion of countr-ions that promotes to swelling of network. As explanation of this phenomenon, the diffusion approach based on ratio of Debye length O of mobile ions and the characteristic size of inhomogeneity region di has been applied [30].

Analysis of physical chemical behaviour of multi-components polymer networks obtained in this work, let us suggest that for thermo-sensitive polyelectrolyte hydrogel containing various size hydrophobic regions, the realization of oscillatory swelling changes are possible. With this goal, the co-polymerization of VEEG, VBE and AA with DVEDEG as a cross agent were performed in water-ethanol medium in the condition of closing to micro aliquation of reaction mixture. The compositions of hydrogels obtained in ethanol and water-ethanol mixtures are practically identical. However, the networks formed in mixed solvent are characterized by the more expressed structure inhomogeneity. The consequence of that is oscillating change of hydrogel volume versus the temperature (Fig. 8).

FIG. 8. Oscillating changing of swelling ratio of VEEG-VBE-AA hydrogel at the temperature increasing. [VEEG]:[VBE]:[ȺA] = 57.6:20.1:17.3 mol%; [CA] = 5 mol%.

FIG. 9. The pH influence on the temperature dependence of swelling ratio of VEEG-VBE-AA hydrogel from the temperature. [VEEG]:[VBE]:[ȺA]:[ɋȺ]= 57,6:20,1:17,3:5,0 mol%; ɪɇ= 1–2,00;

2–3,09; 3–4,29; 4–5,50.

For the multi-components networks, the ratio of ionic and hydrophobic constituents and the swelling behaviour can be regulated by changing the pH and ionic strength of the medium.

With increasing acidity, hydrogels undergo collapse (Fig. 9). Apparently, it is caused by reduction of ionic component contribution to common swelling pressure.

Thus, the new water-swelling co-polymers based on vinyl ethers possess the properties, which are typical for stimuli-sensitive polymers. Their swelling behaviour at the changing of the pH and temperature can be regulated by variation of chemical composition of networks, hydrophilic-hydrophobic balance of macrochains and ionic strength of medium. The possibility to use these hydrogels as a material for controlled drug release systems was shown.

4. BIOMEDICAL INVESTIGATIONS OF POLY (VINYL ETHERS OF