Macromolecular NanotechnologyIn-situ synthesis of polyacrylate grafted carboxymethyl guargum–carbon nanotube membranes for potential application in controlled drug delivery
Graphical abstract
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)
- et al.
Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems
J. Controlled Release
(2014) - et al.
Nanotech approaches to drug delivery and imaging
Drug Discovery Today
(2003) - et al.
Effective use of transdermal drug delivery in children
Adv. Drug Delivery Rev.
(2014) - et al.
Polymeric microdevices for transdermal and subcutaneous drug delivery
Adv. Drug Delivery Rev.
(2012) - et al.
Poly(2-hydroxy-3-phenoxypropylacrylate, 4 hydroxybutyl acrylate, dibutyl maleate) membrane controlled clonidine zero-order release
Eur. J. Pharm. Biopharm.
(2007) - et al.
Synthesis of PVA-CAP-based biomaterial in situ dispersed with Cu nanoparticles and carbon micro-nanofibers for antibiotic drug delivery applications
Biochem. Eng. J.
(2014) - et al.
Sequential design of a novel PVA-based crosslinked ethylenic homopolymer for extended drug delivery
Int. J. Pharm.
(2005) - et al.
A transdermal diltiazem hydrochloride delivery device using multi-walled carbon nanotube/poly(vinyl alcohol) composites
Carbon
(2013) - et al.
Herceptin conjugated PLGA-PHis-PEG pH sensitive nanoparticles for targeted and controlled drug delivery
Int. J. Pharm.
(2015) - et al.
PH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery
Biomaterials
(2013)
Lipid-like trifunctional block copolymers of ethylene oxide and propylene oxide: effective and cytocompatible modulators of intracellular drug delivery
Int. J. Pharm.
Poly(ethylene oxide)–poly(propylene oxide) block copolymer micelles as drug delivery agents: improved hydrosolubility, stability and bioavailability of drugs
Eur. J. Pharm. Biopharm.
Polysaccharides in colon-specific drug delivery
Int. J. Pharm.
Prospective of guar gum and its derivatives as controlled drug delivery systems
Int. J. Biol. Macromol.
Synthesis and characterization of agar-based silver nanoparticles and nanocomposite film with antibacterial applications
Bioresour. Technol.
Interaction of calcium sulfate with xanthan gum: effect on in vitro bioadhesion and drug release behavior from xanthan gum based buccal discs of buspirone
Colloids Surf., B
Influence of mechanical activation on the graft copolymerization of sugarcane bagasse and acrylic acid
Polym. Degrad. Stab.
Cited by (19)
Applications of guar gum polysaccharide for pharmaceutical drug delivery: A review
2024, International Journal of Biological MacromoleculesCarboxymethyl guar gum: A review of synthesis, properties and versatile applications
2022, European Polymer JournalCitation Excerpt :Literature also points to a number of studies relevant to CMGG graft copolymers for biomedical applications, in general and drug delivery, in particular. CMGG grafted poly (diethylene glycol dimethacrylate) / carboxylated-MCNT hydrogels were fabricated for the transdermal delivery of DCF-Na [74]. The pharmaco-kinetics study revealed a burst release of DCF-Na from native CMGG which amounted to about 65% of release within 20 h. However, the hybrid hydrogels clearly retarded the drug release where the most hydrophobic formulation (1 wt% of carboxylated-MCNT) released a mere 16.4% of DCF-Na even after 20 h.
Guar gum-based nanomaterials in drug delivery and biomedical applications
2021, Biopolymer-Based Nanomaterials in Drug Delivery and Biomedical ApplicationsEtherified Moringa oleifera gum as rapid and effective dye adsorbents
2020, Chemical Engineering JournalCitation Excerpt :These have rich pool of various functional groups such as hydroxyl, carboxylic, amines, etc., which act as sites for modification by polymer analogous reactions [4–6] viz. acetylation [7], acryloylation [8,9], etherification [10–12], thiolation [13,14], oxidation [15,16], grafting and crosslinking [17,18], to develop various functional materials with different properties for use in various applications [19–25]. Plant gums, an abundant class of polysaccharides, and their functionalized materials have been reported as adsorbents [3,26–34], drug delivery devices [8,35–42], support materials [43–45], food packaging materials [46,47], additives [48,49], edible coating [50], etc. Though the use of plant gums has continued over the last decades in various applications but there are still several plant gums including Moringa oleifera gum (MOG) that have not been much investigated so far [51–53].
Synthesis and characterization of biopolymer based hybrid hydrogel nanocomposite and study of their electrochemical efficacy
2019, International Journal of Biological MacromoleculesCitation Excerpt :Last few decades, scientists all over the world oriented their research towards the development of biopolymer based hybrid nanocomposites because of their low toxicity and high biodegradability. High natural abundance and low toxicity of biopolymers open different application windows, like biomedical [1], sensor [2], supercapacitor [3], tissue engineering [4], drug delivery [5] etc. Several classes of biopolymer which are in the frontier position of polymer research, out of them polysaccharides are gaining interest for their immense scope of modification and applicability.
Guar gum and its composites as potential materials for diverse applications: A review
2018, Carbohydrate Polymers