Investigation of the effects of orientation on freeze/thawed Polyvinyl alcohol hydrogel properties

Highlights

• The increase of F/T cycles and stretching cycles result a stiffer PVA hydrogel.

• The mechanical stretching cycles increase the orientations on PVA hydrogel.

• The degree of swelling increases with increasing alignment of PVA polymer chains.

• The drug delivery system is best fit with Hixson-Crowell drug release model.

• The drug release rate increases with increasing surface area of stretched hydrogels.

Abstract

Although hydrogels produced via freeze-thawing (F/T) technique have been thoroughly studied in literature, stretching hydrogels in between freeze-thawing cycles could change its properties for drug delivery systems. The PVA hydrogels and Caffeine-contained PVA hydrogels were created by freezing for 20 min using liquid nitrogen and 4 h thawing at 4 °C. The results revealed that the PVA/CAF hydrogel with two F/T cycles followed by two stretching (S) cycles delivered the best response. Furthermore, this sample had the highest degree of crystallinity and Young’s modulus of 36% and 1462 MPa, respectively, which makes this hydrogel very stiff in comparison to all other samples. Moreover, it fits in the Hixson-Crowell drug release model with the highest drug of releasing rate of 15 min, and the highest swelling degree of 470%. Therefore, the study suggests that the number of F/T cycles and stretching cycles influences the properties of the resulting hydrogels and the caffeine release rate.

Introduction

As a biomaterial, hydrogel plays an important role in biomedical applications. Hydrogels have great potential to produce various type of products for wound care, hygiene products, tissue engineering and drug delivery [1]. Hydrogels proved to have the benefits of improving water retention ability and controlled drug release. PVA is a water-soluble synthetic polymer which can form highly swollen gels [2]. The network of Polyvinyl alcohol (PVA) polymer chains contain a large number of hydroxyl groups (−OH) that are responsible for the polymer’s hydrophilicity [3]. These hydrophilic side chains result in a structure capable of trapping water without dissolving in the polymer matrix [2]. Furthermore, the numerous hydroxyl groups present on the backbone of PVA hydrogel offers the possibility of attaching drugs and cell signalling molecules [4]. Therefore, PVA has been identified as a suitable candidate to be used for pharmaceutical applications in releasing biological and medical materials in a controlled way [5]. Yet, there are limitations for use for long-term biomedical applications as membranes or coatings for implantable devices [6].

Orientation can induce a uniaxial polymer chain alignment while maintaining sufficient porosity and water content (>95%). The stretched hydrogels are mechanically stronger and easier to handle than typical hydrogels of the same composition and dimensions [7]. In addition, they can induce alignment for cells seeded on or within the polymer matrix to increase cells adhesion, migration and orientation in the field of tissue regeneration. Wang et al. have investigated cells which are randomly oriented in non-stretched hydrogels. Under the effect of orientation, the growth of cells are aligned almost perpendicularly to the stretching direction [8]. Furthermore, the highly orientated hydrogels exhibit Hixson-Crowell drug release kinetics. This model is normally used to evaluate the dissolution rate and is proportional to the surface area of spherical particles or tablets. It interprets the drug release rate of immediate-release products [9].

The effect of stretching after the formation of freeze/thawed PVA films have been investigated as a function of the stretching ratio by Fukumori and Nakaoki [10], the stretched PVA after annealing at 130 °C shows that the molecular morphology of extended-chain crystals can further improve its tensile strength and Young’s modulus. However, the research indicates that the effect of stretching of PVA hydrogels in between freeze-thawing cycles can exhibit important parameters and physical aspects for modulation of drug delivery as well as mechanical properties. As stretching occurs the polymer chains have a tendency to align in the direction of the stretching and in between the freeze-thawing cycles, physical crosslinking occurs throughout this orientation. In addition, the mechanical and chemical properties of PVA hydrogels are tuneable. The number of F/T cycles, temperature domain of freezing and thawing, stretching ratio and rate, concentration of PVA and drug, as well as molecular weight of PVA can all alter the polymer structure if the aim is to analyse this behaviour [[11], [12], [13]].

For these reasons, in this study, the development of PVA hydrogels have acted as a drug carrier, while caffeine is utilised as a model drug. Caffeine is used to prepare fast dissolving drug delivery systems due to its high water solubility [14,15]. It is widely used as an analgesic adjuvant/mild stimulant in combination with analgesic (e.g. paracetamol, ibuprofen, and aspirin). This type of medicines can augment their bioavailability and deliver rapid onset of action [16,17]. The resultant PVA/CAF hydrogel samples have undergone detailed characterisation of chemical, polymer orientation, mechanical and thermal properties. A drug release study and swelling study were undertaken and compared with the pure PVA hydrogel samples.