Synthesis and Characterisation of Novel Temperature and pH Sensitive Physically Cross-Linked Poly (N-vinylcaprolactam-co-itaconic Acid) Hydrogels for Drug Delivery.

Fallon Fallon,Pezzoli Pezzoli,Higginbotham Higginbotham,Geever Geever,Halligan Halligan

doi:10.3390/gels5030041

Abstract

Previous studies involving poly N-vinylcaprolactam (PNVCL) and itaconic acid (IA) have synthesised the hydrogels with the presence of a solvent and a crosslinker, producing chemically crosslinked hydrogel systems. In this study, however, temperature sensitive PNVCL was physically crosslinked with a pH-sensitive comonomer IA through ultraviolet (UV) free-radical polymerization, without the presence of a solvent, to produce hydrogels with dual sensitivity. The attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy indicated successful polymerisation of the hydrogels. The temperature and pH sensitivity of the hydrogels was investigated. The lower critical solution temperature (LCST) of the gels was determined using the UV spectrometry and it was found that the incorporation of IA decreased the LCST. Rheology was conducted to investigate the mechanical and viscoelastic properties of the hydrogels, with results indicating IA that enhances the mechanical properties of the gels. Swelling studies were carried out at ~20 °C and 37 °C in different buffer solutions simulating the gastrointestinal tract (pH 2.2 and pH 6.8). In acidic conditions, the gels showed gradual increase in swelling while remaining structurally intact. While in basic conditions, the gels had a burst in swelling and began to gradually degrade after 30 min. Results were similar for drug release studies. Acetaminophen was incorporated into the hydrogels. Drug dissolution studies were carried out at 37 °C in pH 2.2 and pH 6.8. It was found that <20% of acetaminophen was released from the gels in pH 2.2, whereas the maximum drug released at pH 6.8 was 74%. Cytotoxicity studies also demonstrated the hydrogels to be highly biocompatible. These results indicate that physically crosslinked P(NVCL-IA) gels possess dual pH and temperature sensitive properties, which may be beneficial for biomedical applications such as drug delivery.

Highlights

Hydrogels that can respond to a number of different environmental factors are commonly referred to as stimuli sensitive hydrogels
Stimuli sensitive polymers are an attractive option for the development of “smart” delivery devices for a wide number of active pharmaceutical ingredients (API) capable of synchronizing their release according to changes in the metabolic states of the body [1]
Crosslinked poly N-vinylcaprolactam (PNVCL) based hydrogels were synthesised via free-radical photopolymerisation based on methods used by Halligan et al (2017) [12]

Summary

Introduction

Hydrogels that can respond to a number of different environmental factors are commonly referred to as stimuli sensitive hydrogels. Gels 2019, 5, 41 the presence of a pH sensitive monomer together with a temperature sensitive monomer allow for the hydrogel to undergo volume changes in response to the pH and temperature [2] This results in a tailored release of the hydrogel to meet specific process or system needs which require the temperature and pH as a factor, such as anti-cancer treatments [3]. Cross-linked gels are of greater interest in modern biomedical applications due to the ability of the gels to degrade and eventually disintegrate and dissolve over time This allows for a less invasive treatment for the patient as the medical device does not need to be removed after use [4]

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Conclusion