DEGRADATION AND INACTIVATION OF CIPROFLOXACIN BY PHOTOCATALYSIS USING TIO2NANOPARTICLES
Imran Hayder, Ishtiaq A.Qazi, M.Ali Awan, Muhammad Arshad Khan,Aftab Turabi
1 Institute of Environmental Science and Engineering, School of Civil and Environmental Engineering,National University of Science & Technology(NUST), Islamabad, Pakistan. 2 Department of Pharmacology, Islam Medical College, Pasroor road, Sialkot, Pakistan
Keywords: Antibiotics, Ciprofloxacin,Bacterial activity, Photocatalysis, TiO2, Nanoparticles.
Abstract

To compare Ciprofloxacin attenuation efficiency, Ciprofloxacin solutions mixed with TiO2nanoparticles were irradiated with two different light sources: a UV lamp and ordinary electric bulb. Insignificant degradation was witnessed when irradiations were made in absence of TiO2. In contrast, prominent Ciprofloxacin degradation was detected in the presence of 0.01 mg/ml of TiO2. Close to 90 % and 70 % of its original concentration was eradicated in 120 minutes when the irradiation basis used was a UV lamp and Ordinary electric bulb respectively. Without the use of TiO2 nanoparticles, irradiation by UV lamp sources was also significant. The antibactacterial activity of chosen microorganisms was radically inhibited when exposed to Ciprofloxacin solution treated with photocatalyst for the short periods of irradiation.

Article Information

Identifiers and Pagination:
Year:2012
Volume:4
First Page:45
Last Page:55
Publisher Id:JAppPharm (2012 ). 4. 45-55
Article History:
Received:September 25, 2011
Accepted:December 9, 2011
Collection year:2011
First Published:January 12, 2012

1.  INTRODUCTION          

  Potential ecological impacts of pharmaceuticals on environment have been detected by recent advancement in analytical chemistry. (Halling-Sørensen et al., 1998).  Antibiotics reach the environment through intentional disposal of surplus drugs to sewage, release to sewage through urine and feces, leaching from landfills and discharges from sewage treatment plants or confined animal farming operations (Daughton, 2000).

Ciprofloxacin is frequently detected class of antibiotics in the environment. It inhibit both Gram-positive (GP) and Gram-negative (GN) bacteria, and commonly used to treat tuberculosis, digestive and urinary tract infections and anthrax Environmental risk studies have estimated environmental loadings of ciprofloxacin from European sewage treatment plants to be as high as 186.2 tones per year in 1999 (Halling-Sorensen, 2000).Monitoring surveys have detected antibiotics in aquatic ecosystems ranging from ng l-1 to mg l-1 concentrations (Giger et al., 2003).  Several studies on ciprofloxacin sorption to clays and minerals have been published (Seremet and MacKay, 2003; Gu and Karthikeyan, 2005).

Ciprofloxacin and levofloxacin account for 65% of the total fluoroquinolone use and represent 3.3 billion dollars in global sales (Datamonitor Strategic Report, 2004). Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class Ciprofloxacin has 69 % bioavailability, 4 hours half life  and renal excretion.

Heterogeneous photocatalysis is an Advanced Oxidation Process(AOPs), can be  utilized to remove many different of pollutants in different phases like liquid and gas  (Hoffmann et al., 1995; Stafford et al., 1996; Hager et al., 2000; Deng et al., 2002; Dunlop et al., 2002; Balasubramanian et al., 2004). The TiO2 (commonly known as titania) is preferentially used for the photocatalytic degradation of organic material due to its different suitable properties such as non-toxicity, low-cost and photochemical stability. The principle of photocatalysis is the formation of nonselective and highly reactive radicals (i.e. hydroxyl radicals (OH.) and the superoxide radical anions (O2·–), which are the primary materials of the oxidative degradation. TiO2 suspension in aqueous environment under irradiation causes an oxidative degradation of many pollutants and mineralizes organic materials into their building blocks i.e. CO2, H2O, and other related inorganic components (Kim et al., 2002; Carp et al., 2004; Florêncio et al., 2004).

The Ultraviolet (UV) radiation enhances the  photocatalytic degradation of organic substrates using TiO2 looks  to be mediated by a number  of reactions initiated by these primary oxidizing radicals, mostly OH. radicals (Ilisz et al., 2002; Kaneco et al., 2004; Chen et al., 2005; Bizani et al., 2006). The photocatalytic efficiency of the UV/TiO2 process is based on a number of factors, e.g. the organic substrate,, light intensity, photoreactor design ,solution composition, and the photocatalyst surface composition (Augugliaro et al., 1995; Chhor et al., 2004). Futhermore, the adsorption of organic substrates onto the surface of TiO2 plays vital role in the photocatalytic degradation (Schmelling et al., 1997; Grzechulska and Morawski, 2002; Uyguner and Bekbölet, 2004).

In this article, Pure TiO2 and Ag doped TiO2 nanoparticles were prepared by Liquid Impregnation technique.  (Sahoo et al., 2005).These nano particles were then studied  for the Ciprofloxacin  as a model drug and  the photocatalytic degradation of the drug by Pure TiO2 and Ag doped TiO2 (i.e 1%, 2%, 3%, 4% & 5%) nanoparticles were examined by UV Spectrophotometer, HPLC and Microbiologically.

 

Fig 1: Chemical structure of Ciprofloxacin HCl

  

2. MATERIAL & METHODS

    2.1 Material

In this study   TiO2 (GPR, BDH Chemicals Ltd. Poole England) was used as TiO2 source for preparing the nanoparticles, and AgNO3 (GR, Merck, Germany) Ciprofloxacin HCl (GR, Merck, Germany) was used as the target  compounds for degradation in this study. TiO2 of Riedel-de-Haen Sigms-Aldrich Lab was purchased.

    2.2  Nanoparticles synthesis

2.2.1 Pure titania nanoparticles

For pure titania nanoparticles, titania (GPR) was taken in a clean china dish. It was placed in a furnace to be calcined at 500oC for 3 hr. The calcined titania was then allowed to cool down slowly so as to attain the nanosized crystal structure.

         2.2.2  Ag- TiO2 Nanoparticles

           Ag-TiO2 nanoparticles were prepared by the Liquid Impregnation Method (Sahoo, et al., 2005). For 1% Ag- TiO2 : 50 gm of TiO2 was poured  into 100 ml dionized water in a 500 ml Pyrex beaker. 1.03 gm of AgNO3 was also added to the suspension for 1% silver doping(molar ratio). Vigorous stirring was used mix the resulting slurry thoroughly and allowed to settle, at room temperature, over night.The  obtained  liquid was dried in an oven at 100oC for 12 hr to evaporate the remaining moisture. The solid material resulting from this step was calcined, at 500oC for 3 hr in a furnace. This resulted in fine particles of silver doped TiO2,  herein after referred to as Ag-TiO1%.

       For 2%, 3%,4% & 5% Ag- TiO2 . 50 gm of TiO2 was poured  into 100 ml dionized water in a 500 ml Pyrex beaker. 2.06 g,.3.09 g, 4.12 g &5.15 g of AgNO3 was also added to the suspension for 2%,3%,4% &5% silver doping(molar ratio) respectively . Vigorous stirring was used mix the resulting slurry thoroughly and allowed to settle, at room temperature, over night.The  obtained  liquid was dried in an oven at 100oC for 12 hr to evaporate the remaining moisture. The solid material resulting from this step was calcined, at 500oC for 3 hr in a furnace. This resulted in fine particles of silver doped TiO2,  herein after referred to as Ag-TiO2%,3%,4% &5% respectively.

2.3  The Photocatalysis Experiment

     The schematic diagram of the experimental setup of photocatalysis experiment is shown in Figure-1.  500mg of high purity Ciprofloxacin HCl powder was dissolved in 100 ml of 0.1 N HCl in a 500 ml beaker and transferred to a 500mL analytical flask. The volume was made up of, with  0.1 N HCl to 500mL to obtain a stock solution of 0.01mg /ml Ciprofloxacin HCl 

    The absorbance reading of this solution was taken by a UV visible spectrophotometer (HACH DR 2400). The absorbance so obtained served as the reference value for \determining the proportionate reduction in the concentration of the Ciprofloxacin, after exposing the solution to UV light and visible light under the conditions of (a) no TiO2, (b) TiO2 and (c) Ag-TiO2 (1%,2%,3%,4% and 5%).

      To 250 ml of the stock solution of Ciprofloxacin HCl, in a china dish, 0.05 g of pure TiO2 nanoparticles or Ag-TiO2 nanoparticles(1%,2%,3%,4% and 5%) were added. The china dish was placed under a UV lamp and allowed to stay exposed to the UV radiation for 2 hours. Its absorbance was then measured at 278 nm on spectrophotometer as described above, while taking into account any dilution effects. In view of the literature reported, experiments were carried out at a pH of 5.8 with UV lamp distance of 5cm from the target surface of the solution in the china dish.Similar experiments were repeated under visible light keeping all other conditions similer.

UV LAMP/Visible light

Figure 2: Experimental Setup for Photocatalysis under UV light/ Visible light

 

2.4. Chemical Analysis

         Samples were taken and absorbance measurements were performed in a Shimadzu UV 1603 spectrophotometer. The ciprofloxacin concentrations was also determined by HPLC using Column 18. Acetonitrile was used as eluent. The ciprofloxacin absorbance was recorded at 278 nm. Total organic carbon was measured in Shimadzu 5000TOC analyzer.

2.5. Antibacterial activity of treated solutions

          Microbiologic assays with irradiated samples were carried out and S.Aureus was used as an assay microorganism.Tripticase agar plates were inoculated with Irradiated Ciprofloxacin samples. After incubation for 24 hours at 37C, the inhibition was noted.

3. Results  & Discussions

    3.1 Ciprofloxacin degradation with TiO2 nanoparticles

          As seen in chart below, a very low ciprofloxascin degradation was observed when it was illuminated in the absence of TiO2.

         In photocatalytic experiments in presence of 0.01 mg/ml , a maximum degradation was obtained under UV lamp illuminations when using Ag-TiO2 nanoparticles. This could be because of the positive effect of silver on the photoactivity of Titania at degradation of Ciprofloxacin that can be clarified by its ability to trap electrons, therefore reducing the recombination of light generated electron-hole pairs at Titania surface.

Figure 2: Degradtion profile of Ciprofloxacin irradiated by presence and absence of TiO2nanoparticles and Ag-TiO2 nanoparticles

 

                 Significant degradation was observed when ciprofloxacin was treated with the TiO2 nanoparticles with the UV lamp but less as compared to the Ag-TiO2 in the presence of UV lamp. It was also observed that by increasing the percentages of silver in Ag-TiO2 i.e from 1% onward, better degradation was noted. Our results encouraged the use of Ag doped TiO2   for the degadation of Ciprofloxacin.

Table 1: Showing the level of degradation

Lamp

Nanoparticles

Degradtion of Ciprofloxacin

Visible

No TiO2 nanoparticels

Insignificant degradation

UV

No TiO2 nanoparticels

Significant degradation

Visbible light

With TiO2 nanoparticles

Major degradation

UV

With Ag-TiO2

Maximum Degradation

 

      Comparative photocatalytic degradation of Ciprofloxacin was also investigated in the presence of UV light.  As it is clear from the chart below, Ag-TiO2 nanoparticles show better results  as compared to pure TiO2 nano particles.

 

 

Figure3: Comparitive photocatalytic degradation of Ciprofloxacin with pure and Ag doped Titania Nanoparticles.

 Similarly, results by HPlC clearly indicate that better degradation was observed with silver doped titania as compared to only Titanai nanoparticles. Compartive descriptive charts below show the detail of results.Same patern confirmed by FTIR results in Figures 7,8 and 9.

Table 2: Degradation of 0.01 ppm Ciprofloxacin by 1-5% Ag doped titania & undoped titania under Uvlight determined by HPLC

Name

# of Peak

Ret. Time

Area

Height

Area %

Ciprofloxacin Stock

1

12.868

625824

24846

100

Ciprofloxacin+UV+TiO2

7

12.986

641290

25502

88.561

Ciproflox+UV+1%Ag-TiO2

10

12.428

46939

2036

28.258

Ciproflox+UV+2%Ag-TiO2

8

12.123

45979

1669

24.430

Ciproflox+UV+3%Ag-TiO2

3

5.024

10046

415

16.212

Ciproflox+UV+4%Ag-TiO2

5

12.614

122159

4855

30.530

Ciproflox+UV+5%Ag-TiO2

6

12.613

145364

5756

52.792

Ciproflox+UV only

6

12.572

123721

9934

22

Table3: Degradation of 0.01 ppm Ciprofloxacin by 1-5% Ag doped titania & undoped titania under Visible light determined by HPLC

Name

# of Peak

Ret.Time

Area

Height

Area %

Ciproflox

1

12.868

625824

24846

100

Cipro+TiO2+Light

6

12.964

205614

8312

61.363

Cipro+1%Ag-TiO2+light

12

12.257

21785

916

10.565

Cipro+2%Ag-TiO2+light

4

12.111

142516

4906

53.085

Cipro+3%Ag-TiO2+light

6

12.653

139568

5526

46.236

Cipro+4%Ag-TiO2+light

6

12.593

132630

5298

38.172

Cipro+5%Ag-TiO2+light

3

12.596

17431

722

17.818

Cipro+light only

3

12.706

52657

1314

17.982

3.2 Effect of the TiO2 photocatalysis on the antibacterial activity

     Experiemnts with selected bacteria (S.aureus) were perfomed to determine the antibacterial activity of ciprofloxacin during photocatalysis. Assays were done on bacterial inoculated agar plates.

Figure3: Zone of inhibition of ciprofloxacin drug

 

                The effect on biological activity for the irradiated sapmes was observed by noting the inhibition halo formed around the drop seed on the agar plate. It was observed that when untreated ciprofloxacin solution was used, inhibition zone of 5.5 cm was observed. But when ciprofloxacin solution treated with TiO2 nanoparticles was used no kind of zone of inhition was noted. And the same with Ag-TiO2, mean no zone of inhihibition was noted when ciprofloxacin solution treated with Ag-TiO2was used. This could be explained that original drug ciprofloxacin has been modified and degraded.

    

Figur4: :FTIR results of  Ciprofloxacin with no TiO2 nanoparticles


Figure5: FTIR results of  Ciprofloxacin with TiO2 nanoparticles

                                                

Figure 6: FTIR results of  Ciprofloxacin with Ag-TiO2 nanoparticles

 

        It is also important to note that even on UV light treated ciprofloxacin solution where minimum amount of drug was degraded, did not show any kind of zone of inhibition. This support the concept that the intermediated product of photocatalytic process do not represent any antibacterial activity.

4. CONCLUSION

      The Ciprofloxacin structure was effectively degraded by TiO2 photocatalysis using different kinds of light sources and TiO2 nanoparticles. More Oxidation was noted when UV lamp along with Ag-TiO2 nanoparticles were used. This could be because of the positive effect of silver on the photoactivity of Titania at degradation of Ciprofloxacin that can be clarified by its ability to trap electrons, therefore reducing the recombination of light generated electron-hole pairs at Titania surface.

     The most remarkable conclusion is that as a result of treatment of ciprofloxacin with TiO2,Ag-TiO2 nanoparticles and UV light, degraded ciprofloxacin and its products do not present antibacterial activity against S.aureus. Successful degradation  of the ciprofloxacin antibiotics was found in this studies. Therefore, TiO2-based photocatalysis is feasible way to inactivate the ciprofloxacin drug, as a pretreatment prior to further biological treatments. 

 

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Prof. Dr. Cornelia M. Keck (Philipps-Universität Marburg)
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Welcome to the research group of Prof. Dr. Cornelia M. Keck in Marburg. Cornelia M. Keck is a pharmacist and obtained her PhD in 2006 from the Freie Universität (FU) in Berlin. In 2009 she was appointed as Adjunct Professor for Pharmaceutical and Nutritional Nanotechnology at the University Putra Malaysia (UPM) and in 2011 she obtained her Venia legendi (Habilitation) at the Freie Universität Berlin and was appointed as a Professor for Pharmacology and Pharmaceutics at the University of Applied Sciences Kaiserslautern. Since 2016 she is Professor of Pharmaceutics and Biopharmaceutics at the Philipps-Universität Marburg. Her field of research is the development and characterization of innovative nanocarriers for improved delivery of poorly soluble actives for healthcare and cosmetics. Prof. Keck is executive board member of the German Association of Nanotechnology (Deutscher Verband Nanotechnologie), Vize-chairman of the unit „Dermocosmetics“ at the German Society of Dermopharmacy, active member in many pharmaceutical societies and member of the BfR Committee for Cosmetics at the Federal Institute for Risk Assessment (BfR).

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