Preparation and physicochemical assessment of rutin-loaded gelatin nanoparticles

Research Article

Shahriar Shahi ¹, Elham Ahmadian ², Nazanin Fathi ³, Aziz Eftekhari ⁴, Rovshan Khalilov^5,6, * , Solmaz Maleki Dizaj ^1,*

¹Dental and Periodontal Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

²Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

³Immonology Research Center, Tehran University of Medical Sciences

⁴Pharmacology and Toxicology Department, Maragheh University of Medical Sciences, Maragheh, Iran

⁵Joint Ukrainian-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych Ukraine & Baku, Azerbaijan

⁶ Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan

Abstract

The encapsulation technique is one of the most prevalent strategies to preserve the natural ingredients, like rutin. Actually, this strategy can enhance the flavonoid content as well as create an appropriate compound that possesses new physical and functional characteristics. The objective of the current study is preparation and also evaluation of rutin-loaded gelatin nanoparticles. Based on the obtained results, the prepared nanoparticles presented the suitable physicochemical properties accompanied with high drug encapsulation efficiency. Accordingly, rutin-incorporated gelatin nanoparticles can be as an effective alternative for this compound.

Keywords: Rutin, Gelatin, Nanoparticles, Physicochemical properties

1. Introduction

During recent years, natural products like curcumin, rutin, quercetin, resveratrol have been increasingly investigated in biomedicine owing to their high safety, cost-effectiveness and extensive biological effects. Among the different existed groups in the natural products, flavonoids are as widespread groups in these materials that have indicated favorable impacts to treat the various human diseases (1). Various plant kingdoms contain flavonoids which encompass benzo-pyrone derivatives (2). The diverse segments of the plants including seeds, roots, fruits and flowers possess different levels of flavonoids. The therapeutic properties of flavonoids like reactive oxygen scavenging, anti-inflammatory, immunomodulatory, antimicrobial and cancer treating activities has turned them into valuable potential drugs (3, 4). It well documented that various therapeutic effects of these compounds can be attributed to their chemical structure and reducing specifications has been shown to be responsible for. In addition to the mentioned properties, flavonoids could exhibit synergistic effects in combination with other antioxidants including vitamins and carotenoids (5).

The chemical structure of rutin (2-(3,4-dihydroxyphenyl)-4,5-dihydroxy-3-[3,4,5trihydroxy-6-[(3,4,5-trihydroxy-6 methyl-oxan-2-yl)oxymethyl]oxan-2-yl]oxy-chromen-7-one (Figure 1) is produced from the combination of flavonol quercetin and disaccharide rutinose (6). In general, it is found in vegetables, citrus fruits and plant-derived beverages. It was reported that rutin is also a compound with antioxidant activity, which has capacity of the reducing in the case of different oxidizing species such as superoxide, peroxy and hydroxyl radicals (7). Furthermore, it possesses pharmacological effects, for example, anticancer, antimicrobial, anti-inflammatory effects (8).  Rutin has shown superiorities in diabetes, hypolipidemia and different tumors, as well (9). It has been shown that rutin counteracts against some flavonoids which exert prooxidant activities because of catalyzing oxygen radical generation (10). Moreover, rutin offers advantages rather than aglycones that create cytotoxic and mutagenic effects and thus their pharmacological use is restricted. Regarding, rutin is considered a non-oxidizable and non-toxic chemical that could be useful in biomedical applications.

Recently, the design of a novel drug delivery system using nanotechnology has opened new perspectives for the future of the pharmaceutical industry. Decreased cytotoxicity, as well as increased bioavailability of active ingredients, are the major advantages of the nanoparticulate drug delivery systems (11-13). In this research, our group is concentrated on the preparation and physicochemical evaluation of rutin-loaded gelatin nanoparticles.

Figure 1. Chemical structure of rutin.

2. Materials and methods

Materials

Gelatin, Rutin, Glutaraldehyde were provided from Sigma-Aldrich (St. Louis, United States), and Acetone was obtained from Temad Kala (Tehran, Iran). All other reagents were in analytical grade.

2.1. Preparing of rutin-gelatin nanoparticles

The synthesis of rutin-gelatin nanoparticles was conducted through the precipitation method. First, 1 g of gelatin was dissolved in 13 ml of distilled water at 40 ° C. Then, 13 ml of acetone was gradually added to the solution as anti-solvent and in this step, the pH of the solution was adjusted at 11 using sodium hydroxide, as well. In the next stage, 6 mg of rutin was added to the solution. After that, 80 ml acetone was added dropwise into the solution. Finally, 100 µl of glutaraldehyde was added as cross-linker and accordingly, gelatin-rutin nanoparticles precipitated.

3. Characterization of rutin-gelatin nanoparticles

3.1. Particle size distribution and surface charge measurements

A Zeta-sizer Nano ZS (Malvern Instruments, Worcestershire, U.K.) was employed to measure the mean particle sizes, polydispersity indexes (PDI) as well as zeta-potentials (surface charge) of the prepared nanoparticles.

3.2. Encapsulation efficiency

Encapsulation efficiency (EE) was calculated using equations 1. In equation 1, the total amount of rutin (mg) is the rutin amount applied to fabricate the nanoparticle and the free rutin amount was measured via the supernatant found after nanoparticle fabrication. A calibration curve was plotted at 354 nm. It needs to considerate that rutin amount in the upper phases was obtained after centrifugation through the calibration curve.

3.3. In vitro release measurements

In vitro release investigations were conducted in phosphate buffered saline (PBS) at 37 °C, pH =7.4.

3.4. Statistical analysis

The results were presented as mean ± standard deviation.

4. Results and discussion

As mentioned in the Introduction section, the encapsulation of active agents in polymeric nanoparticles could create opportunities including protection of sensitive bioactive compounds, increase of their solubility, improvement of their bioavailability (14, 15). Moreover, the factors that inhibit the use of bioflavonoids is found in abundance in fruits and vegetables consumed in daily human life, such as poor water solubility, instability, absorption, and permeability, were aimed to be overcome by encapsulating polymeric nanoparticles in this research.

The nanoparticles with a particle size of 260 nm (Figure 2), negative zeta potential of -23 mV (Figure 3) and EE of 95 % were obtained. Based on the thermal analysis data, an interaction occurred between rutin and gelatin through a crosslinking reaction, this role could be ascribed to the synergic association of rutin and the UV filters. As well, a sustained release profile was produced during 96 h for rutin-loaded nanoparticles compared to pure rutin (Figures 4 and 5).

Figure 2. Particle size distribution for rutin-loaded gelatin nanoparticles.	Figure 3. Zeta potential amount for rutin-loaded gelatin nanoparticles.
Figure 4. The release profile for pure rutin.	Figure 5. The release profile for rutin-loaded gelatin nanoparticles.

4. Conclusion

In the current research study, the encapsulation approach was employed to produce rutin-laded gelatin nanoparticles with the object of bioavailability improvement. Based on the obtained results, rutin-encapsulated gelatin nanoparticles can be an effective alternative for this compound.

Acknowledgments

This article was written based on a dataset from a thesis registered at Dental and Periodontal Research Center, Tabriz University of Medical Sciences (number 61355). The Vice Chancellor for Research at Tabriz University of Medical Sciences provided financial support for this research that is greatly acknowledged.

Conflict of interest

The author has no conflict of interest in this paper.

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HOW TO CITE

Shahi, S., Ahmadian, E., Fathi, N., Eftekhari, A., Khalilov, R., & Maleki Dizaj, S. (2019). Preparation and physicochemical assessment of rutin-loaded gelatin nanoparticles. Journal of Advanced Chemical and Pharmaceutical Materials (JACPM), 2(2), 138-142. Retrieved from http://advchempharm.ir/journal/index.php/JACPM/article/view/91

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