Controlled release of amoxicillin and antioxidant potential of gold nanoparticles-xanthan gum/poly (Acrylic acid) biodegradable nanocomposite

Highlights

• MW assisted AuNPs/XG/Poly(AA) biodegradable nanocomposite is synthesized successfully.

• This hydrogel nanocomposite can be used for application of controlled release of amoxicillin.

• The resultant nanocomposite shows good releasing profile.

• The synthesized nanocomposite is pH responsive, the diffusion rate is tune with pH.

• Synthesis method provides the nanocomposite for controlled drug delivery having antioxidant potential.

Abstract

In the present study, the green microwave assisted synthesis of gold nanoparticles imbedded in XG/Poly(AA) biodegradable nanocomposite for controlled delivery of amoxicillin has been reported. The evidence of in-situ synthesis of gold nanoparticles by plant extract of Nepeta leucophylla as reducing agent inside the polymer matrix, grafting of acrylic acid (AA) onto backbone XG, surface morphology, crystallinity, thermal properties and loading of amoxicillin inside the MW-AuNPs/XG/Poly(AA) nanocomposite are investigated using various characterization techniques, such as, UV–Vis, XRD, FTIR, TGA/DSC, FE-SEM, EDX, TEM, DLS and Nitrogen adsorption-desorption isotherms (BET studies). The biodegradation test of synthesized nanocomposite has been performed by soil burial method for 75 days. The evidence of biodegradability of MW-AuNPs/XG/Poly(AA) nanocomposite is confirmed by FTIR and FE-SEM micrographs. The release profiles of amoxicillin drug from synthesized nanocomposite has been investigated for different pH (2.4, 7.0 and 9.2) at 37$°C$ using Korsmeyer–Peppas model. Here, the maximum drug loading efficiency is found to be about 85% and release of drug is large in basic medium as compare to acidic and neutral. It is expected that the present work may provide a noble method for synthesis of biodegradable nanocomposite with decent antioxidant potential for controlled release of amoxicillin.

Introduction

The development of stimuli-responsive smart hydrogels nanocomposite for the controlled release of drug delivery is an emergent field of research due to their sensitivity towards, temperature, light, pH, electric and magnetic stimulus. However, pH is the most significant factor for drug release in the human body. Polysaccharides based hydrogels are played a significant role in drug release due to their distinct properties, such as, hydrophilicity, biocompatibility, biodegradability, elasticity and admirable water uptake capacity [1,2]. The poor mechanical strength and enormous solubility is the chief disadvantage of these materials. Hence, synthesis of mechanically strong smart hydrogel is required. Grafting of these polymer with synthetic monomers and incorporation of metal nanoparticles inside the polymer matrix is an effective technique for improving its strength. Metal nanoparticles-biopolymer nanocomposites are some imperative categories of these materials which show amazing properties [3].

Gold is one of the first metals to have been discovered and used for medicinal purposes since ancient time till now. Colloidal gold has been used for the cure of various diseases, such as syphilis, leprosy, plague, epilepsy and diarrhea [[4], [5], [6]]. Gold nanoparticles (AuNPs) show tremendous behaviour with a reduction in size and they possess a large specific surface area, a high fraction of surface atoms and large surface energy. Also, they have Surface Plasmonic Resonance effect, stability in biological media, adsorption of near infrared light and large adsorptive potential [7,8]. These nanoparticles are providing the strong linkage of drug molecules with polymer for further maximizing the efficiency of drug release at the desired site, minutest side effects and lower dosing frequency [9,10]. The antioxidant property of AuNPs has recently became a fascinating research area, which makes it an appropriate candidate as compare to synthetic antioxidants. Pooja et al., 2014 [11], reported the use of xanthan gum for the synthesis of the gold nanoparticles. The synthesized AuNPs is used as drug delivery carrier for doxorubicin hydrochloride and its toxicity studies revealed its biocompatible and non-toxic nature. These distinctive properties of metal nanoparticles motivate us for the synthesis of biopolymer nanocomposites for the antioxidant potential and controlled drug delivery.

Amoxicillin ($\alpha$ -amino-hydroxybenzylpenicillin) is an extensively used semisynthetic, orally absorbed antibiotic and its chemical structure is shown in Fig. 1(a) [12]. The residency time of amoxicillin in stomach is very short, duo to its degradation in gastric acid (pH 1.2). The $\beta$ -lactam ring present in structure in is more susceptible to hydrolytic degradation when the pH is significantly lower than isoelectric point (pH 4.8). Hence, amoxicillin capsules are unable to deliver the drug at desired site with effective concentration. In order to overcome this drawback, the drug is encapsulated inside polymer nanocomposite and taken by following oral administration route. This route has been considered to be most suitable due to its ease of administration, high patient compliance, least sterility constraints and flexibility in the design of the dosage form [13,14].

A lot of efforts have been made by researchers for the formation of these nanocomposite and tailoring of the properties of natural polysaccharides for controlled drug delivery application [[15], [16], [17], [18], [19], [20]]. Till dates, various synthesis methods of polymerization, such as, thermal [21], redox, E-beams [22], ultra violet (UV) [23] and $\gamma$ -rays [24] are available in literature. The high energy of $\gamma$ -ray having large penetration depth causes radiolysis and small penetration depth of ultra violet (UV) is limited to only surface grafting. Due to this reason, the ultra violet and gamma ray's methods are not effective for grafting the backbone material with synthetic monomers. Currently, the application of microwave irradiation for synthesis of polymer nanocomposite is an emerging polymerization technique as compare to other conventional methods [25,26]. This is due to the, large penetrating ability, quicker heating, large reaction rate, high efficiency and productivity and significantly enriched properties of products [27]. Hence, microwave assisted synthesis is promising for effective synthesis of polymeric nanocomposite.

Xanthan gum (XG) is an anionic, natural edible polysaccharide derived from Xanthomonas campestris and its chemical structure is shown in Fig. 1(b). It has been extensively used in the pharmaceutical industries because of their excellent properties such as high molecular weight, high solubility, pH stability, nontoxicity, and gelling characteristics [28]. Acrylic acid (AA) is a prospective monomer used in preparation of the grafted copolymer. The number of studies have been reported which direct towards the usage of natural polysaccharides polymer matrix and its composite for drug delivery applications [[29], [30], [31], [32], [33]]. The chemical structure of polysaccharides reveal that they have functional groups, such as, –OH, –NH₂, –CONH₂, –COOH, and –SO₃, which make them active.

From above discussion, it can be concluded that a lot of efforts have been made in the past by many researchers to synthesize the polymer and its nanocomposite as a controlled device. In the present study, an attempt has been made to fabricate microwave assisted biodegradable nanocomposite based on XG using gold nanoparticles as multifunctional agents by using quite innovative MW irradiation technique. The in-situ synthesis of gold nanoparticles has been carried out by novel plant extract, i.e., Nepeta leucophylla, which enriched the synthesized nanocomposite with good antioxidant potential. Then, the application of MW-XG/Poly(AA)/AuNPs nanocomposite hydrogel as device for controlled release of Amoxicillin is demonstrated. The drug loaded hydrogel nanocomposite is allowed to load the drug through swelling and to release the drug through deswelling by placing them into double deionized water. Biodegradation test of synthesized nanocomposite has been also carried out by soil burial method. It is expected that the present study may provide the biodegradable nanocomposite with decent antioxidant potential for controlled release of amoxicillin.