Elsevier

European Polymer Journal

Volume 74, January 2016, Pages 13-25
European Polymer Journal

Macromolecular Nanotechnology
In-situ synthesis of polyacrylate grafted carboxymethyl guargum–carbon nanotube membranes for potential application in controlled drug delivery

https://doi.org/10.1016/j.eurpolymj.2015.11.007Get rights and content

Highlights

Abstract

Sustainable hydrophobic membranes were prepared in-situ from the composites of poly (diethylene glycol dimethacrylate) grafted carboxymethyl guargum (CMG-g-PDEGDMA)/carboxy functionalized multiwalled carbon nanotube (f-MWCNT). The composite membranes were applied for transdermal delivery of hydrophobic diclofenac sodium. The uniform dispersion of f-MWCNT resulted into stronger–matrix filler interaction, particularly at 1 wt.% f-MWCNT concentration. The membrane was most hydrophobic and least drug eluting. At higher f-MWCNT loading i.e. at 2 and 3 wt.% the membranes were less hydrophobic and faster drug eluting as a consequence of relatively poor matrix–filler interaction and copolymer wrapping. The most hydrophobic formulation (1 wt.%) had released 16.4% of the encapsulated drug, while the least (3 wt.%) had released 42% after 20 h study in a Franz diffusion cell under physiological condition.

Introduction

Transdermal delivery or patch therapy has received maximum compliance of a patient because of its elementary, non-invasive approach [1], [2]. Apart from being the mildest drug delivery approach, it further resists secondary infections through obstructing fast pass metabolism and thus eliminates toxicity [3], [4], [5], [6], [7]. The sustained release of the drug molecules eventually reduces therapeutic complications between intra and inter patient variability. A transdermal patch is composed of (i) a liner, which protects the patch during storage and is removed before use, (ii) the drug, which is encapsulated within the patch in the sol state, (iii) an adhesive layer, which adheres the components of the patch together and also adheres the patch to the skin, (iv) the membrane, which encapsulates the drug and controls the release and (v) the backing, which protects the patch from the external environment [8]. Membrane is the key component of a patch since it acts as drug encapsulator cum sustained releaser. Majority of the membranes is prepared from different synthetic polymers such as various acrylates [9], [10], [11], [12], poly (vinyl alcohol) [13], [14], [15], poly (ethylene glycol) [16], [17], and poly (propylene oxide) [18], [19] mainly due to advantages of high mechanical strength and stability. However, due to increased environmental awareness, many biopolymers are experimented of late as an alternate membrane polymer. Some latest example, include guar gum [20], [21], locust bean gum [22], agar agar [23], [24], xanthan gum [25], etc. Although polysaccharides are excellent viscosifiers yet the membranes are not mechanically stable. In addition, the hygroscopic nature of the polysaccharides wanes the level of control over the drug release rate since the absorption of water molecules facilitates faster elution of the drug molecules [26]. So, it is important that the polysaccharide membranes should maintain optimum hydrophobicity for both better drug encapsulation and controlled release. In this project, we have used CMG instead of guargum, due to its higher water solubility than the later, and grafted it with PDEGDMA (CMG-g-PDEGDMA) to impart hydrophobic character. It was apprehended that increase in synthetic content in CMG could improve environmental as well as mechanical stabilities of the membranes [27], [28]. The material world has dramatically changed with the advent of polymer nanotechnology. Addition of various nanofillers in polymers has drastically improved various physico-mechanical properties [29], [30]. f-MWCNT is an important nanofiller which has been used primarily to improve thermal and electrical conductivities in various thermoplastic polymer composites [31], [32], [33]. However, it has not been investigated in the area of medicinal biotechnology so far mainly due to its cytotoxic effects [34]. The reason that we have selected f-MWCNT because the proposed membranes will be used in vitro, in particular, outside the body, where the chances of contamination with cellular masses is minimized. f-MWCNT was added in the grafting stage to facilitate uniform dispersion in the absence of a compatibilizer. f-MWCNT could be an excellent adsorbent for the drug molecules, hence could increase the encapsulation efficacy of the membranes. On top of that, it could further promote the hydrophobicity of the membranes. The newly developed membranes were used to encapsulate and regulate the release of a model hydrophobic drug, diclofenac sodium or only diclofenac. Diclofenac has been the most popular pain killer drug for a long period of time. Withal, it is connected with certain vital issues like limited plasma solubility, extremely low half-life (2.5 h) and chronic side effects from long term administration. Controlled delivery through the skin could resolve most of these problems, in particular, extension of the half-life period of the drug molecules which in turn cuts the effects of drug overload. The noble composite membranes were thoroughly characterized and the release kinetics were investigated in a Franz diffusion cell under physiological condition. The role of both PDEGDMA and f-MWCNT have been discussed in the manuscript for understanding the release data of the drug molecules.

Section snippets

Materials

CMG with a degree of substitution 0.6 was generously supplied by the Hindustan Gums and Chemicals Ltd., Haryana, India. DEGDMA was a gifted sample from Berger Paints India Ltd., Howrah, India. f-MWCNT with 2 wt.% carboxy functionalization (outer diameter 10–20 nm, length 10–30 μm, purity >95 wt.% and ash <1.5 wt.%) was generously supplied by the Cheap Tubes Inc. Barttelboro, USA. Benzoyl peroxide, the grafting initiator and hydroquinone the quencher, of, standard laboratory grades, were purchased

Studies on grafting yield and reduced viscosity

Grafting yield and reduced viscosity of the copolymers formed with different concentrations of benzoyl peroxide are plotted in Fig. 1a. A maximum of 64% yield was achieved at 0.1 wt.% initiator content while after that it decreased with further rise in the peroxide content. Since low initiator concentration favors formation of higher molecular weight polymers, the lowest initiator concentration i.e. 0.1 wt.%, has produced the maximum level of grafting. Further increase in concentration probably

Conclusion

The present investigation demonstrated excellent capability of the hydrogel nanocomposites in controlling the release of a very important painkiller drug diclofenac sodium. It was primarily due to in-situ addition of f-MWCNT which aided good dispersion within the copolymer matrix without any external compatibilizer. Presence of f-MWCNT raised the hydrophobic character of the membranes and resisted faster swelling unlike both neat CMG and CMG-g-PDEGDMA membranes. At 1 wt.% in-situ concentration,

Acknowledgement

The first author (A. Giri) gratefully recognizes the financial support offered by the University of Calcutta under U.R.F. and TEQIP (II) schemes to carry out this research work.

References (35)

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