Next Article in Journal
Electrochemical Capacitance of CNF–Ti3C2Tx MXene-Based Composite Cryogels in Different Electrolyte Solutions for an Eco-Friendly Supercapacitor
Previous Article in Journal
Alginate–Gelatin Hydrogel Scaffold Model for Hypoxia Induction in Glioblastoma Embedded Spheroids
Previous Article in Special Issue
A Multifunctional γ-Polyglutamic Acid Hydrogel for Combined Tumor Photothermal and Chemotherapy
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Gels
Volume 11
Issue 4
10.3390/gels11040264
gels-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Investigation of PVA Matrix Hydrogel Loaded with Centaurea cyanus Extract for Wound Dressing Applications: Morphology, Drug Release, Antibacterial Efficiency, and In Vitro Evaluation

by
Melis Abahuni Ucar
1,
Enis Muhammet Gul
2,
Deniz Uygunoz
2,
Emek Moroydor Derun
2,* and
Mehmet Burcin Piskin
1
1
Department of Bioengineering, Yildiz Technical University, Istanbul 38000, Turkey
2
Department of Chemical Engineering, Yildiz Technical University, Istanbul 38000, Turkey
*
Author to whom correspondence should be addressed.
Gels 2025, 11(4), 264; https://doi.org/10.3390/gels11040264
Submission received: 10 March 2025 / Revised: 21 March 2025 / Accepted: 24 March 2025 / Published: 2 April 2025
(This article belongs to the Special Issue Hydrogels, Microgels, and Nanogels: From Fundamentals to Applications (2nd Edition))
Browse Figures
Versions Notes

Abstract

:
A polyvinyl alcohol (PVA) matrix hydrogel loaded with Centaurea cyanus extract was created for transdermal wound healing. Secondary metabolites, antibacterial properties, and the cytotoxicity of C. cyanus extract were investigated. The secondary metabolite profiles of the extract were determined by liquid chromatography–mass spectrometry (LC-MS) technique. It was determined that the extract has metabolites such as quinic acid, caffeoylquinic acid, kaempferol, etc., which contribute to the steps of wound healing. The extract had significant activity against Staphylococcus aureus when compared with ampicillin antibiotic and showed an inhibition zone of 16.9 mm ± 0.8, whereas ampicillin’s inhibition zone was 15.8 mm ± 0.8. The extract did not exhibit cytotoxic effects on 3T3-L1 (CL173) healthy skin fibroblasts, maintained cell viability for 72 h, and exhibited a 19% proliferative effect. Fourier-transform infrared spectroscopy, scanning electron microscopy, ultraviolet visible spectrophotometer, tensile strength analyses, in vitro release, and physicochemical tests were conducted. It was seen that the surfaces of the samples are smooth and homogeneous, patches had a significant amount of water absorption capacity, and 79% of the extract was released within the first 24 h of application; consequently, these results indicate that C. cyanus might be used in wound healing with its antibacterial, growth-promoting properties.

1. Introduction

Wound healing is a physiological, biochemical, and cellular process that involves all body systems that comprise the following four interacting steps: hemostasis, inflammation (1–4 days), proliferation (4–21 days), and tissue remodeling (21 days–2 years), respectively [1,2,3,4]. Wound treatment has always had an important role in the health field. Wounds that do not heal require long treatments and decrease the quality of life for the patient. Current methods, such as negative pressure therapy and surgery, are not always efficient treatments [5]; however, traditional dry wound dressings do not provide a moist environment for wound healing and do not have high antibacterial properties. An ideal wound dressing should be biocompatible and provide a moist environment to the wound. It should be easily removed from the tissue and must ensure adequate gas exchange and maintain an adequate wound surface temperature [6]. Transdermal skin patches are modern ideal wound dressings that meet these preferred features. Transdermal drug delivery systems, also known as transdermal patches, are dosage forms designed to deliver a therapeutically effective amount of active ingredient to the patient’s skin and, thus, to the bloodstream over time [7,8,9]. Plant extracts are preferred because they are natural and provide active ingredients [10].
Asteraceae is one of the plant families most used in wound treatment. Plants belonging to the Asteraceae family have ethnopharmacological importance in many societies, such as India, Turkey, Nigeria, Nepal, South Africa, Britain, and Ireland [11]. Due to this importance, various plants from this family have been studied for their pharmacological activities, such as anti-inflammatory, antimicrobial, and healing activities [12,13,14]. The therapeutic potential of some species, such as Calendula officinalis L., Achillea millefolium L., and Neurolaena lobata (L.), in wound care has been reported in the literature [15,16]. It has been stated that their activities are related to their ability to promote the proliferation of keratinocytes and, thus, the remodeling of the extracellular matrix [17,18]. Although there are various studies in the literature on other species belonging to the Asteraceae family, there is limited information about Centaurea cyanus. The following information is generally related to the determination of bioactive components, taxonomic classification, and antioxidant, antimicrobial, and anti-inflammatory properties of C. cyanus [19,20,21,22,23,24,25,26]. C. cyanus has traditionally been used in areas such as eye care and wound healing. In one study, the upper and lower parts of the capitulum of C. cyanus were examined and compared in terms of their chemical composition and bioactive properties. It has been observed that the flower parts are rich in tocopherol, citric acid, and apigenin derivatives, while the lower parts are rich in quinic acid and syringic acid. As a result, the lower part of the plant has been shown to exhibit antioxidant and antibacterial properties that can be used in different food or pharmaceutical formulations [27].
To the best of our knowledge, the published literature did not provide information on a therapeutic transdermal patch containing C. cyanus extract; therefore, the aim of the present study was to design a polyvinyl alcohol (PVA) matrix transdermal patch involving C. cyanus extract. The developed transdermal patches and the plant extract used were subjected to a series of analyses comprising liquid chromatography mass spectrometry (LC-MS), antibacterial tests, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), ultraviolet visible spectrophotometer (UV-Vis), tensile strength tests, and several of other physicochemical tests.

2. Results and Discussion

2.1. LC-MS Results

It was observed that the effectiveness of the hypericin and hyperforin components was minimal (Table 1). It was concluded that the effectiveness of C. cyanus extract was derived from the quinic acid, kaempferol, quercetin-O-(O-galloyl)-hexoside, caffeoylquinic acid, hyperoside, and adhyperforin components observed at m/z = 191, 285, 615, 353, 463, and 549, respectively, when compared with that in the literature [28,29,30,31,32,33,34] (Figure 1).
These metabolites have the potential to positively affect the phases of wound healing. The coagulating property of quinic acid contributes to the hemostasis phase. Kaempferol exhibits high antioxidant properties, interacts with reactive oxygen species (ROS) that cause tissue damage, and reduces the ROS rate. In a study conducted using rats, it has been reported that the quercetin component contributes to dermal wound healing by increasing growth factors and also forms a collagen matrix; therefore, because of the quercetin component in C. cyanus extract, it would develop new tissue consisting of collagen and the extracellular matrix, as a contribution to the formation of new tissue in the proliferative phase. Because caffeoylquinic acid has anti-inflammatory and antihyperlipidemic properties, it is predicted to have a positive effect during wound healing by preventing inflammation [35,36,37,38].

2.2. MTT Results

According to the results of the cytotoxicity experiment performed to evaluate the plant extract interaction in skin tissue, the IC50 value for the analyzed sample was determined to be >20 µg/mL. The results of evaluating the sample for three different time periods and six different concentrations are shown separately in Figure 2.
According to MTT analysis results, C. cyanus extract did not cause 50% cell viability inhibition at the studied concentrations and was not considered toxic within the studied concentration range. Compared with the control group, a 19% proliferative effect was observed at a concentration of 10 µg/mL and 15% at a concentration of 20 µg/mL. This shows that C. cyanus extract may have positive effects on the wound healing process.

2.3. Antibacterial Activity Results

Figure 3 shows the inhibition zone formations of C. cyanus extract on E. coli and S. aureus cultures, and the diameters of the inhibition zones were measured. It was shown in Table 2.
The results showed that the extract had antibacterial activity on both E. coli and S. aureus. It was also observed that the extract had more antibacterial activity on S. aureus than on the ampicillin, which was the control group. This antibacterial activity resulted from the antimicrobial and antibacterial properties of the quinic acid, kaempferol, quercetin, hyperforin, and hypericin metabolites of C. cyanus extract [39,40,41].

2.4. Characterization of Herbal Transdermal Patch

2.4.1. SEM

It was observed that the surfaces of the samples were smooth and homogeneous, and shown in Figure 4. It was observed that the herbal formulation exhibited a porous structure, which contributes to tissue healing by ensuring oxygen permeability, absorbing wound exudate, creating entry and exit pathways for water and active substances, and providing a moist environment to the wound [42].

2.4.2. FTIR

FTIR spectra of the pure and herbal transdermal patches were determined using FTIR and shown in Figure 5. The pure PVA transdermal patch spectrum exhibited characteristic peaks at 3272, 2939, 1654, 1416, 1094, and 849 cm−1, which are related to O-H, C-H, C=O, C-H, C-O, and C-C stretching [43,44]. After adding C. cyanus extract, the characteristic peaks of PVA were still observed, which meant that the extract did not affect the main molecular structure of PVA. In addition, with the addition of the extract, new peaks were observed at 1567 and 1237 cm−1 wavelengths, which correspond to C=C and C-C stretching vibrations in the aromatic ring of flavonoids [45,46,47]. In general, it was observed by FTIR analysis that the extract was successfully incorporated into the PVA hydrogel.

2.4.3. Tensile Strength Test

The results of the tensile strength test are shown in Figure 6. The breaking tensile strength of the pure PVA transdermal patch was 1.87 MPa, and that of the herbal transdermal patch was 1.37 MPa. This situation occurs as a result of the decrease in the polymer solution ratio in the formulation and the increase in porosity with the addition of the plant extract.

2.4.4. Determination of Transdermal Patch Thickness

The thicknesses of synthesized samples are shown in Table 3. The average thickness of the pure PVA transdermal patch was 0.147 ± 0.03 mm, and that of the herbal transdermal patch was 0.16 ± 0.03 mm. It was clearly observed that herbal patch thickness was greater than that of the pure patch.

2.4.5. Weight Uniformity

The weights of the synthesized samples are shown in Table 3. It was observed that the weights of both the pure PVA transdermal patch and the herbal patch were uniform throughout the transdermal patch.

2.4.6. Moisture Content Percentage

The moisture contents of the synthesized samples are shown in Table 3. The percent moisture content of transdermal films may vary depending on the amount of polymer solution in their formulation. In addition, the plant extracts they contain and their amounts are also factors that affect the moisture content in the formulation. In this context, the data obtained were found to be compatible with those in the literature [48,49].

2.4.7. Percentage of Dehumidification

The percentages of dehumidification of the synthesized samples are shown in Table 3. It was determined that the moisture absorption percentage of the formulation containing the plant extract was relatively higher than that of the pure patch. The data obtained were compatible with those in the literature [50].

2.4.8. Percent Swelling Rate

The percent swelling ratio test findings of the optimum synthesized samples are shown in Figure 7. For skin renewal and wound healing to occur, the wound area must be moist, and the wound dressing must absorb wound fluid and exudate; therefore, the swelling feature is important. Pure PVA transdermal patches exhibited considerable water absorption capacity between 108.2 and 148.5%, and the herbal transdermal patches exhibited water absorption capacity between 97.4 and 135.2%, which suggested an important potential for these patches in applications that require substantial moisture retention. It was observed that the resistance of transdermal films to swelling increased in the herbal formulation. This positive result was created from the interaction between the polymer and plant extract in the formulation. The findings obtained are close to those in the literature.

2.4.9. Determination of Surface pH

The pH of each synthesized sample is shown in Table 3. It was observed that the average pH of both samples was comparable and compatible with skin pH.

2.4.10. In Vitro Release Profile

The standard curve of the extract was obtained using different concentrations of C. cyanus and the UV-Vis spectrophotometer, and shown in Figure 8.
The cumulative release amount of extract is shown in Figure 9. A burst release at first and then a linear and balanced release graph was observed. Extract release within the first 60 min was 19.17%, 70.83% at 360 min, and at the 24th hour, it was 79%. The 70% release that occurred within the first 6 h plays an important role in preventing bacterial growth and reducing the effect of ROS in the initial phase of wound healing [51,52].

3. Conclusions

In the present study, a PVA matrix transdermal wound dressing containing C. cyanus extract was successfully fabricated and evaluated for its wound-care potential. It was observed that the extract has secondary metabolites, such as quinic acid, caffeoylquinic acid, and kaempferol, which contributed to the steps in wound healing. In addition, it was observed that the extract had significant activity against S. aureus as well as ampicillin antibiotic, which has an inhibition zone of 15.8 mm ± 0.8 and an inhibition zone of 16.9 mm ± 0.8. The extract did not exhibit cytotoxic effects on 3T3-L1 (CL173) healthy skin fibroblasts, did not cause 50% cell viability inhibition at the studied concentrations, maintained cell viability for 72 h, and exhibited 19% proliferative effect at a concentration of 10 µg/mL and 15% at a concentration of 20 µg/mL. According to FTIR results, the PVA functional groups were confirmed for both the pure and extract-loaded samples. SEM analysis showed that the extract-loaded formulation had a porous structure. The tensile test revealed the durability of the synthesized sample. Physicochemical test results showed compatibility with that in the literature. In addition, it was observed that the patches had a significant amount of water absorption capacity. Moreover, 79% of the extract was released within the first 24 h, and 70% release occurred within the first 6 h, which plays an important role in preventing bacterial growth and reducing the effect of ROS in the initial phase of wound healing. In light of this information, it was suggested that the material was successfully synthesized and that C. cyanus might be used in wound healing because of its antibacterial, growth-promoting properties, and would be a new alternative to today’s wound treatments. In conclusion, the wound healing potential of PVA matrix hydrogel loaded with Centaurea cyanus extract was demonstrated in this study. These findings underline the need for further research and development in this area.

4. Materials and Methods

4.1. Materials

Centaurea cyanus plants were obtained from a local sapling market in Istanbul, Turkey. The microorganism strains of Staphylococcus aureus (ATCC 25923) and Escherichia coli (ATCC 25922) were used as test bacteria. Nutrient agar, nutrient broth, and absolute ethanol (C2H5OH) with a purity of >99.8% and molecular weight of 46 g/mol were purchased from Merck (Darmstadt, Germany). PVA with a purity of 99%+ hydrolized and molecular weight of Mw 85,000–124,000 was obtained from Sigma-Aldrich (Burlington, MA, USA). Glycerine with a purity of 99.5% and molecular weight of 92.10 g/mol was supplied from Tekkim (Bursa, Istanbul). Phosphate buffer solution (PBS) at pH 7.4 was retrieved from Nacalai Tesque (Kyoto, Japan). Distilled water was used throughout all experiments.

4.2. Synthesis Procedure

4.2.1. Plant Extract

The dried plants were ground using a grinding device. Soxhlet extraction using a Velp Scientifica Ser 148, Italy, was used as the preferred extraction method. Ethanol was used as the extraction solvent. The device consisted of the following three steps: (1) 60 min immersion, (2) 60 min washing, and (3) 10 min recovery at 210 °C. In the first step, the plants were soaked in the boiling extraction solvent. In the second step, the plants were removed from the solvent and washed with hot ethanol. In the final step, a large proportion of the solvent was recovered by distillation. The resulting plant extract was stored in amber glass bottles at room temperature in a desiccator.

4.2.2. Fabrication of Herbal Transdermal Patch

The transdermal patches were prepared using the solvent-casting method. Pure PVA solution was prepared using the appropriate temperature and 750 rpm stirring speed. Homogenization was achieved by taking a certain amount of PVA solution according to the formulation and adding the appropriate amount of plasticizer (glycerin). Then, 1.5 mL of the plant extract was added to the solution, mixed (30 min at 750 rpm), and set into an ultrasonic bath. The prepared samples were placed in Petri dishes and left to dry in an oven.

4.3. Characterization

4.3.1. LC-MS Method

LC-MS was used to determine the hypericin and hyperforin, phytochemical components in the plant extracts that are the most common metabolites in Asteraceae, according to the literature [53]. The C. cyanus extract was analyzed using an Agilent 6530 LC MS-TOF system, Santa Clara, CA, USA. Standard samples of hypericin and hyperforin were used, and their quantitative determination was performed using tandem mass spectrometry (MS/MS) operated in negative mode. The quantification was based on the quantity and purity values indicated on the standard sample certificates. The amount of hypericin in the analytical standard sample was 10 mg with 88.90% purity. The amount of hyperforin in the analytical standard was 250 µg with >85% purity. The hypericin and hyperforin analytes were determined using a C. cyanus (02-MK) sample. An ACE 3 µm Sil column was used, and the mobile phases comprised phase A (100 mM ammonium formate in distilled water [pH 3]/acetonitrile [19:1 v/v]) and Phase B (100 mM ammonium formate in distilled water [pH 3]/acetonitrile [1:19 v/v]). The column temperature was 40 °C.

4.3.2. MTT Test

MTT analysis was conducted to evaluate the cytotoxicity of the desired extract. 3T3-L1 (CL173) healthy skin fibroblast systems were used. The live broadcast rate was run using quantitative colorimetry with a spectrophotometer with a microplate reader. After the cells were incubated in an oven with 5% CO2 at 37 °C for 24 h, six different concentrations of the samples were prepared with the new medium (final distribution 20–0.5 µg/mL) and repeated in at least two technical and three biological replicates. It was applied and incubated for 24, 48, and 72 h. The percent viability fractions of the concentration were calculated based on the control group. The one-half maximal inhibitory concentration (IC50) values were calculated by probit analysis using the GraphPad Prism 5 program (Windows 5.04). One-way analysis of variance and Tukey’s post hoc test were used for statistical analyses.

4.3.3. Antibacterial Activity

The antibacterial activity of C. cyanus extract was determined using the disc diffusion method. E. coli ATCC 25922, a gram-negative bacterium, and S. aureus ATCC 25923, a gram-positive bacterium, were used for the study, along with an ampicillin antibiotic disc as a control.

4.3.4. Characterization of Herbal Transdermal Patch

SEM

The surface morphology of the patches was analyzed using SEM, and a Zeiss EVO LS 10, Oberkochen, Germany, at 5.00 kX magnification with an accelerating voltage of 10 kV was used for analyses.

FTIR

FTIR analysis was conducted to gather information about the structure of the raw materials used in the formulation and forming of the developed transdermal patches. The analysis was conducted using the attenuated total reflectance technique on the Perkin Elmer-Spectrum 100 device, Waltham, MA, USA, at a wave range of 4000–650 cm−1.

Tensile Strength Test

The Instron 5982 Electromechanical Universal Testing Machine, Wycombe, UK, was used for the analysis. The sample reference length was determined to be 10 mm, and the cross-head speed was determined to be 10 mm/min.

Determination of Film Thickness

The thickness of the developed transdermal films was measured using a digital micrometer by taking samples from three different points on the film. The average thickness was then determined along with the standard deviation [54,55].

Weight Uniformity

Circular sections with a diameter of 2 cm were taken from three different regions of the prepared patches and weighed on an analytical balance. The average weight was then determined along with the standard deviation [56].

Moisture Content Percentage

The moisture content of the produced transdermal patches was determined using the Radwag brand moisture analyzer, Poland. The moisture content of the transdermal films was determined by the initial weight of the sample before drying, which was calculated as the percentage difference between the sample weights before and after drying. The average percent moisture content was calculated for three replicates along with the standard deviation [56].

Percentage of Dehumidification

The prepared transdermal patch formulations were weighed on an analytical balance and kept in a desiccator containing saturated potassium chloride solution for 24 h to ensure 84% Rhesus factor, after which the transdermal formulations were weighed again, and the moisture absorption percentages were determined using Equation 1 as follows [56]:
Moisture absorption percentage (%) = (final weight − initial weight)/initial weight × 100

Percent Swelling Rate

Circular sections of 2 cm in diameter were cut from three different parts of the produced patches and weighed on an analytical balance, after which the samples were placed in Petri dishes containing distilled water and subjected to swelling tests at 10 min intervals for a total of 30 min. The average swelling ratio was determined for three different samples [56].

Determination of Surface pH

Circular sections with a diameter of 2 cm were taken from the developed transdermal films, and the pH was measured using a digital pH meter. All tests were repeated three times, and the average was calculated along with the standard deviation.

In Vitro Release Profile

For the in vitro release study, a Franz diffusion cell was used with cellulose acetate membrane, using a PBS solution with a pH of 7.4 as the release medium and a temperature of 37 ± 1 °C [57]. Ultraviolet measurements were made by taking samples at specific time intervals (0, 15, and 30 min and 1, 2, 3, 4, 5, 6, and 24 h), and the concentrations of the samples was calculated using a calibration curve. The calibration curve was created by determining the values of the extract at different concentrations corresponding to 206 nm, which is the wavelength at the maximum absorption point.

Author Contributions

Conceptualization, M.A.U.; methodology, M.A.U., E.M.G., D.U., E.M.D. and M.B.P.; validation, E.M.D. and M.B.P.; formal analysis, M.A.U., E.M.G., D.U., E.M.D. and M.B.P.; investigation, M.A.U., E.M.G. and D.U.; resources, M.A.U., E.M.G., D.U., E.M.D. and M.B.P.; data curation, M.A.U., E.M.G., D.U., E.M.D. and M.B.P.; writing—original draft preparation, M.A.U.; writing—review and editing, M.A.U., E.M.G. and D.U.; visualization, M.A.U., E.M.G. and D.U.; supervision, E.M.D. and M.B.P.; project administration, E.M.D. and M.B.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by Yıldız Technical University Scientific Research Project Coordination Research Fund, grant number FBA-2022-5005.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions of this study are included in the article. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Liang, Y.; He, J.; Guo, B. Functional Hydrogels as Wound Dressing to Enhance Wound Healing. ACS Nano J. 2021, 15, 12687–12722. [Google Scholar] [CrossRef]
  2. Elias, P.M.; Feingold, K.R. Skin Barrier; Taylor & Francis: New York, NY, USA, 2006. [Google Scholar]
  3. Dąbrowska, A.K.; Spano, F.; Derler, S.; Adlhart, C.; Spencer, N.D.; Rossi, R.M. The Relationship between skin function, barrier properties, and body-dependent factors. Ski. Res. Technol. 2018, 24, 165–174. [Google Scholar] [CrossRef]
  4. Montagna, W. The Structure and Function of Skin; Elsevier: Amsterdam, The Netherlands, 2012. [Google Scholar]
  5. Eming, S.A.; Martin, P.; Tomic-Canic, M. Wound repair and regeneration: Mechanisms, signaling, and translation. Sci. Transl. Med. 2014, 6, 265sr6. [Google Scholar] [CrossRef] [PubMed]
  6. Ulusoy, A.; Dikmen, N. Hidrojellerin Tıpta Uygulamaları. Arşiv Kaynak Tarama Derg. 2020, 29, 129–137. [Google Scholar] [CrossRef]
  7. Prajapati, S.T.; Patel, G.C.; Patel, N.C. Formulation and Evaluation of Transdermal Patch of Repaglinide. ISRN Pharm. 2011, 13, 274–285. [Google Scholar] [CrossRef]
  8. Akhtar, M.F.; Hanif, M.; Ranjha, N.M. Methods of synthesis of hydrogels … A Review. Saudi Pharm. J. 2016, 24, 554–559. [Google Scholar] [CrossRef]
  9. Xu, Y.; Chen, H.; Fang, Y.; Wu, J. Hydrogel Combined with Phototherapy in Wound Healing. Adv. Healthc. Mater. 2022, 11, e2200494. [Google Scholar] [CrossRef]
  10. Gavan, A.; Colobatiu, L.; Hanganu, D.; Bogdan, C.; Olah, N.K.; Achim, M.; Mirel, S. Development and Evaluation of Hydrogel Wound Dressings Loaded with Herbal Extracts. Processes 2022, 10, 242. [Google Scholar] [CrossRef]
  11. Suntar, I. The Medicinal Value of Asteraceae Family Plants in Terms of Wound Healing Activity. FABAD J. Pharm. Sci. 2014, 39, 21–31. [Google Scholar]
  12. George Kallivalappil, G.; Kuttan, G. Evaluation of the anti inflammatory and urotoxicity ameliorative effects of gamma-humulene containing active fraction of Emilia sonchifolia (L.) DC. Inflammopharmacology 2019, 27, 409–420. [Google Scholar] [CrossRef]
  13. Ghaderi, A.; Sonboli, A. Chemical composition and antimicrobial activity of the essential oil of Tanacetum walteri (Anthemideae-Asteraceae) from Iran. Nat. Prod. Res. 2018, 33, 1787–1790. [Google Scholar] [CrossRef] [PubMed]
  14. Ozbilgin, S.; Akkol, E.K.; Ergene Oz, B.; Ilhan, M.; Saltan, G.; Acikara, O.B.; Tekin, M.; Keleş, H.; Suntar, I. In vivo activity assessment of some Tanacetum species used as traditional wound healer along with identification of the phytochemical profile by a new validated HPLC method. Iran. J. Basic Med. Sci. 2018, 21, 145–152. [Google Scholar] [CrossRef] [PubMed]
  15. Parente, L.M.; Lino Junior Rde, S.; Tresvenzol, L.M.; Vinaud, M.C.; DePaula, J.R.; Paulo, N.M. Wound healing and anti-inflammatory effect in animal models of Calendula officinalis L. growing in Brazil. Evid.-Based Complement. Altern. Med. 2012, 2012, 375671. [Google Scholar] [CrossRef]
  16. Nayak, B.S.; Ramlogan, S.; Chalapathi Rao, A.; Maharaj, S. Neurolaena lobata L. promotes wound healing in Sprague Dawley rats. Int. J. Appl. Basic Med. Res. 2014, 4, 106–110. [Google Scholar] [CrossRef]
  17. Speroni, E.; Govoni, P.; Guizzardi, S.; Renzulli, C.; Guerra, M.C. Anti inflammatory and cicatrizing activity of Echinacea pallida Nutt. root extract. J. Ethnopharmacol. 2002, 79, 265–272. [Google Scholar] [CrossRef]
  18. Rosa Ados, S.; Bandeira, L.G.; Monte-Alto-Costa, A.; Romana-Souza, B. Supplementation with olive oil, but not fish oil, improves cutaneous wound healing in stressed mice. Wound Repair Regen. 2014, 22, 537–547. [Google Scholar] [CrossRef]
  19. Takeda, K.; Tominaga, S. The Anthocyanin in Blue Flowers of Centaurea cyanus, The Botanical Magazine. J. Plant Res. 1983, 96, 359–363. [Google Scholar]
  20. Pirvui, L.; Bubueanu, C.; Panteli, M.; Petcu, L.; Coprean, D. Centaurea cyanus L. polysaccharides and polyphenols cooperation in achieving strong rat gastric ulcer protection. Open Chem. 2015, 13, 910–921. [Google Scholar]
  21. Hazırı, A.; Faiku, F.; Rudhani, İ.; Mehmeti, İ.; Motori, D. Antibacterial activity of different extracts of Centaurea cyanus (L.) growing wild in Kosovo. Orient. J. Chem. 2017, 33, 1636–1641. [Google Scholar] [CrossRef]
  22. Denga, C.; Lib, S.; Feng, C.; Honga, Y.; Huanga, H.; Wanga, J.; Wang, L.; Daia, S. Metabolite and gene expression analysis reveal the molecular mechanism for petal colour variation in six Centaurea cyanus cultivars. Plant Physiol. Biochem. 2019, 142, 22–23. [Google Scholar] [CrossRef]
  23. Lockowandt, L.; Pinela, J.; Roriza, C.; Pereira, C.; Abreu, R.; Calhelha, R.; Alves, M.; Barros, L.; Bredol, M.; Ferreira, I. Chemical features and bioactivities of cornflower (Centaurea cyanus L.) capitula: The blue flowers and the unexplored non-edible part. Ind. Crops Prod. 2019, 128, 496–503. [Google Scholar] [CrossRef]
  24. Keyvanloo Shahrestanaki, M.; Bagheri, M.; Ghanadian, M.; Aghaei, M.; Jafari, S.M. Centaurea cyanus extracted 13-O-acetylsolstitialin A decrease Bax/Bcl-2 ratio and expression of cyclin D1/Cdk-4 to induce apoptosis and cell cycle arrest in MCF-7 and MDA-MB-231 breast cancer cell lines. J. Cell. Biochem. 2019, 120, 18309–18319. [Google Scholar] [CrossRef] [PubMed]
  25. Fernandesa, L.; Pereiraa, J.A.; Saraiva, J.A.; Ramalhosa, E.; Casal, S. Phytochemical characterization of Borago officinalis L. and Centaurea cyanus L. during flower development. Food Res. Int. 2019, 123, 771–778. [Google Scholar] [CrossRef]
  26. Haratym, W.; Chmielewska, E.; Konarska, A. Microstructural and histochemical analysis of aboveground organs of Centaurea cyanus used in herbal medicine. Protoplasma 2020, 257, 285–298. [Google Scholar] [CrossRef]
  27. Karamenderes, C.; Khan, S.; Tekwani, B.; Jacob, M.; Khan, I. Antiprotozoal and antimicrobial activities of Centaurea species growing in Turkey. Pharm. Biol. 2006, 44, 534–539. [Google Scholar] [CrossRef]
  28. Khan, A.B.; Khan, A.; Khan, M.K.; Braga, V. Preparation and properties of high sheared poly(vinyl alcohol)/chitosan blended hydrogels films with Lawsonia inermis extract as wound dressing. J. Drug Deliv. Sci. Technol. 2020, 61, 102227. [Google Scholar] [CrossRef]
  29. Andrade, P.; Seabra, M.; Valentao, P.; Areias, F. Simultaneous determination of flavonoids, phenolic acids, and coumarins in seven medicinal species by HPLC/diode-array detector. J. Liq. Chromatogr. Relat. Technol. 1998, 21, 2813–2820. [Google Scholar] [CrossRef]
  30. Mauri, P.; Pietta, P. High performance liquid chromatography/electrospray mass spectrometry of Hypericum perforatum extracts. Rapid Commun. Mass Spectrom. 2000, 14, 95–99. [Google Scholar]
  31. Tatsis, E.; Boeren, S.; Exarchou, V.; Troganis, A.; Vervoort, J.; Gerothanassis, I. Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS. Phytochemistry 2006, 67, 383–393. [Google Scholar] [CrossRef]
  32. Kajdzanoska, M.; Gjamovski, V.; Stefova, M. HPLC-DAD-ESI-MSn identification of phenolic compounds in cultivated strawberries from Macedonia. Maced. J. Chem. Chem. Eng. 2010, 29, 181–194. [Google Scholar] [CrossRef]
  33. Zhang, J.; Zhang, Q.; Li, N.; Wang, Z.; Lu, J.; Qiao, Y. Diagnostic fragment-ion-based and extension strategy coupled to DFIs intensity analysis for identification of chlorogenic acids isomers in Flos Lonicerae Japonicae by HPLC-ESI-MSn. Talanta 2013, 115, 1–9. [Google Scholar] [CrossRef]
  34. Souza, L.; Cipriani, T.; Iacomini, M.; Gorin, P.; Sassaki, G. HPLC/ESI-MS and NMR analysis of flavonoids and tannins in bioactive extract from leaves of Maytenus ilicifolia. J. Pharm. Biomed. Anal. 2008, 47, 59–67. [Google Scholar] [CrossRef] [PubMed]
  35. Saldanha, L.; Vilegas, W.; Dokkedal, A. Characterization of flavonoids and phenolic acids in Myrcia bella Cambess. using FIA-ESI-IT-MSn and HPLC-PAD-ESI-IT-MS combined with NMR. Molecules 2013, 18, 8402–8416. [Google Scholar] [CrossRef] [PubMed]
  36. Aksoy, H.; Özakpınar Bingöl, Ö. Yara iyileşmesi ve oksidatif stres. Marmara Pharm. J. 2014, 18, 153–155. [Google Scholar] [CrossRef]
  37. Gomathi, K.; Gopinath, D.; Ahmed, M.; Jayakumar, R. Quercetin incorporated collagen matrices for dermal wound healing processes in rat. Biomaterials 2003, 24, 2767–2772. [Google Scholar] [CrossRef]
  38. Samancı Dursun, H.M. TGF-β, Hesperidin ve Kuersetinin MCF-7 Hücresinin uPA Aktivitesi Üzerine ve PAI-1 Ekspresyonuna Etkisi. Master’s Thesis, Selçuklu University, Konya, Türkiye, 2015. [Google Scholar]
  39. Mutlubaş, H.; Özdemir, Z.Ö. Hypericum perforatum’un geleneksel tıp alanındaki uygulamaları. J. Integr. Anatol. Med. 2020, 1, 10–22. [Google Scholar]
  40. Yıldırım, M. Effect of kaempferol in medicinal plants on LPS-induced THP-1 macrophages. Mersin Üniversitesi Tıp Fakültesi Lokman Hekim Tıp Tarihi Ve Folk. Tıp Derg. 2023, 13, 118–124. [Google Scholar] [CrossRef]
  41. Wang, S.; Yao, J.; Zhou, B.; Yang, J.; Chaudry, M.T.; Wang, M.; Xiao, F.; Li, Y.; Yin, W. Bacteriostatic effect of quercetin as an antibiotic alternative in vivo and its antibacterial mechanism in vitro. J. Food Prot. 2018, 81, 68–78. [Google Scholar] [CrossRef]
  42. Doersch, K.; Rogers, K. The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression. Exp. Biol. Med. 2017, 242, 1424–1431. [Google Scholar] [CrossRef]
  43. Zheng, Y.; Liang, Y.; Zhang, D.; Sun, X.; Liang, L.; Li, J.; Liu, Y.-N. Gelatin-based hydrogels blended with gellan as an injectable wound dressing. ACS Omega 2018, 3, 4766–4775. [Google Scholar] [CrossRef]
  44. Alrowaili, Z.A.; Ezzeldien, M.; Mohammed, M.I.; Yahia, I.S. Design of a low-cost laser cut-off filter using carmine dye-doped PVA polymeric composite films. Results Phys. 2020, 16, 103203. [Google Scholar] [CrossRef]
  45. Jabbar, W.A.; Habubi, N.F.; Chiad, S.S. Optical characterization of silver-doped poly (vinyl alcohol) films. J. Ark. Acad. Sci. 2010, 64, 120–125. [Google Scholar]
  46. Mohan, P.R.; Sreelakshmi, G.; Muraleedharan, C.V.; Joseph, R. Water soluble complexes of curcumin with cyclodextrins: Characterization by FT-Raman spectroscopy. Vib. Spectrosc. 2012, 62, 77–84. [Google Scholar] [CrossRef]
  47. Rozylo, R.; Szymanska-Chargor, M.; Gawlik-Gziki, U.; Dziki, D. Spectroscopic, mineral, and antioxidant characteristics of blue-colored powders prepared from cornflower aqueous extracts. Food Chem. 2021, 346, 128889. [Google Scholar] [CrossRef]
  48. Chopra, H.; Bibi, S.; Kumar, S.; Khan, M.S.; Kumar, P.; Singh, I. Preparation and evaluation of chitosan/PVA-based hydrogel films loaded with honey for wound healing application. Gels 2022, 8, 111. [Google Scholar] [CrossRef]
  49. Kanjani, B.; Rai, G.; Gilhotra, R.; Kohli, S.; Pandey, V.; Khalsa, R. Formulation design, optimization, and characterization of herbal bioactive-loaded transdermal patch: The state of the art. SGVU J. Pharm. Res. Educ. 2018, 3, 279–288. [Google Scholar]
  50. Saleem, M.N.; Idris, M. Formulation design and development of a Unani transdermal patch for antiemetic therapy and its pharmaceutical evaluation. Scientifica 2016, 2016, 7602347. [Google Scholar] [CrossRef]
  51. Tuntiyasawasdikul, S.; Sripanidkulchai, B. Development and clinical trials on anti-inflammatory effect of transdermal patch containing a combination of Kaempferia parviflora and Curcuma longa extracts. J. Drug Deliv. Sci. Technol. 2022, 68, 103093. [Google Scholar] [CrossRef]
  52. Lan, X.; Liu, Y.; Wang, Y.; Tian, F.; Miao, X.; Wang, H.; Tang, Y. Coaxial electrospun PVA/PCL nanofibers with dual release of tea polyphenols and ε-poly (L-lysine) as antioxidant and antibacterial wound dressing materials. Int. J. Pharm. 2021, 601, 120525. [Google Scholar] [CrossRef]
  53. Biberoglu, G. Mass spectrometry and medically usage. Türkiye Klin. J. Med. Sci. 2003, 23, 491–498. [Google Scholar]
  54. Patel, A.V.; Shah, B.N. Transdermal drug delivery system: A review. Int. J. Pharm. Sci. 2018, 9, 378–390. [Google Scholar]
  55. Sutheesh, T. Formulation and Evaluation of Transdermal Patch of Aqueous Extract of Azadirachta Indica a Juss. Master’s Thesis, The Tamil Nadu Dr. M.G.R. Medical University, Chennai, India, 2017. [Google Scholar]
  56. Monton, C.; Sampaopan, Y.; Pichayakorn, W.; Panrat, K.; Suksaeree, J. Herbal transdermal patches made from optimized polyvinyl alcohol blended film: Herbal extraction process, film properties, and in vitro study. J. Drug Deliv. Sci. Technol. 2022, 69, 103170. [Google Scholar] [CrossRef]
  57. Malaiya, M.K.; Jain, A.; Pooja, H.; Jain, A.; Jain, D. Controlled delivery of rivastigmine using transdermal patch for effective management of Alzheimer’s disease. J. Drug Deliv. Sci. Technol. 2018, 45, 408–414. [Google Scholar] [CrossRef]
Gels 11 00264 g001
Figure 1. (a–d) The liquid chromatography mass spectrometry results obtained for the components of Centaurea Cyanus.
Figure 1. (a–d) The liquid chromatography mass spectrometry results obtained for the components of Centaurea Cyanus.
Gels 11 00264 g001
Gels 11 00264 g002
Figure 2. (A) Effects of the sample on NIH-3T3 cell viability after 24 h of exposure, (B) effects of the sample on NIH-3T3 cell viability after 48 h of exposure, and (C) effects of the sample on NIH-3T3 cell viability after 72 h of exposure. Notes: Data are mean ± standard deviation, * p < 0.05, and *** p < 0.001 versus the control group.
Figure 2. (A) Effects of the sample on NIH-3T3 cell viability after 24 h of exposure, (B) effects of the sample on NIH-3T3 cell viability after 48 h of exposure, and (C) effects of the sample on NIH-3T3 cell viability after 72 h of exposure. Notes: Data are mean ± standard deviation, * p < 0.05, and *** p < 0.001 versus the control group.
Gels 11 00264 g002
Gels 11 00264 g003
Figure 3. Interaction of Centaurea cyanus extract on Staphylococcus aureus (A) and Escherichia coli (B) cultures.
Figure 3. Interaction of Centaurea cyanus extract on Staphylococcus aureus (A) and Escherichia coli (B) cultures.
Gels 11 00264 g003
Gels 11 00264 g004
Figure 4. Scanning electron microscopy of (A) Pure polyvinyl alcohol transdermal patch image (5 KX), (B) herbal transdermal patch image (5 KX), and (C) post-release image of herbal transdermal patch after 24 h of dissolution (5 KX).
Figure 4. Scanning electron microscopy of (A) Pure polyvinyl alcohol transdermal patch image (5 KX), (B) herbal transdermal patch image (5 KX), and (C) post-release image of herbal transdermal patch after 24 h of dissolution (5 KX).
Gels 11 00264 g004
Gels 11 00264 g005
Figure 5. Fourier-transform infrared spectroscopy results of pure polyvinyl alcohol transdermal patch and herbal transdermal patch.
Figure 5. Fourier-transform infrared spectroscopy results of pure polyvinyl alcohol transdermal patch and herbal transdermal patch.
Gels 11 00264 g005
Gels 11 00264 g006
Figure 6. Tensile strength results of (A) pure polyvinyl alcohol transdermal patch and (B) herbal transdermal patch.
Figure 6. Tensile strength results of (A) pure polyvinyl alcohol transdermal patch and (B) herbal transdermal patch.
Gels 11 00264 g006
Gels 11 00264 g007
Figure 7. Percent swelling rate test. Notes: n = 3, mean ± SD.
Figure 7. Percent swelling rate test. Notes: n = 3, mean ± SD.
Gels 11 00264 g007
Gels 11 00264 g008
Figure 8. The standard calibration curve of the extract.
Figure 8. The standard calibration curve of the extract.
Gels 11 00264 g008
Gels 11 00264 g009
Figure 9. The cumulative release profile of the extract.
Figure 9. The cumulative release profile of the extract.
Gels 11 00264 g009
Table 1. Determination of hypericin and hyperforin of Centaurea cyanus extract.
Table 1. Determination of hypericin and hyperforin of Centaurea cyanus extract.
PlantHypericin Amount (ng mL−1) Hyperforin (ng mL−1)
Centaurea cyanus12.5 ± 5.2 *43.2 ± 0.7 *
* n = 3, mean ± SD.
Table 2. Inhibition zone diameter created by Centaurea cyanus extract on Escherichia coli and Staphylococcus aureus.
Table 2. Inhibition zone diameter created by Centaurea cyanus extract on Escherichia coli and Staphylococcus aureus.
SampleE. coli (mm)S. aureus (mm)
Centaurea cyanus8.2 ± 0.5 *16.9 ± 0.8 *
Ampicillin17.1 ± 0.6 *15.8 ± 0.8 *
* n = 3, mean ± SD.
Table 3. Physicochemical test results.
Table 3. Physicochemical test results.
ParametersPure PVA PatchHerbal Patch
Patch thickness (mm)0.147 ± 0.03 *0.16 ± 0.03 *
Weight uniformity (g)0.0555 ± 0.01 *0.0775 ± 0.01 *
Moisture content percentage (%)8.33 *10.87 *
Humidification percentage (%)2.73 *3.91 *
Surface pH6.87 ± 0.03 *6.92 ± 0.03 *
* n = 3, mean ± SD.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Abahuni Ucar, M.; Gul, E.M.; Uygunoz, D.; Derun, E.M.; Piskin, M.B. Investigation of PVA Matrix Hydrogel Loaded with Centaurea cyanus Extract for Wound Dressing Applications: Morphology, Drug Release, Antibacterial Efficiency, and In Vitro Evaluation. Gels 2025, 11, 264. https://doi.org/10.3390/gels11040264

AMA Style

Abahuni Ucar M, Gul EM, Uygunoz D, Derun EM, Piskin MB. Investigation of PVA Matrix Hydrogel Loaded with Centaurea cyanus Extract for Wound Dressing Applications: Morphology, Drug Release, Antibacterial Efficiency, and In Vitro Evaluation. Gels. 2025; 11(4):264. https://doi.org/10.3390/gels11040264

Chicago/Turabian Style

Abahuni Ucar, Melis, Enis Muhammet Gul, Deniz Uygunoz, Emek Moroydor Derun, and Mehmet Burcin Piskin. 2025. "Investigation of PVA Matrix Hydrogel Loaded with Centaurea cyanus Extract for Wound Dressing Applications: Morphology, Drug Release, Antibacterial Efficiency, and In Vitro Evaluation" Gels 11, no. 4: 264. https://doi.org/10.3390/gels11040264

APA Style

Abahuni Ucar, M., Gul, E. M., Uygunoz, D., Derun, E. M., & Piskin, M. B. (2025). Investigation of PVA Matrix Hydrogel Loaded with Centaurea cyanus Extract for Wound Dressing Applications: Morphology, Drug Release, Antibacterial Efficiency, and In Vitro Evaluation. Gels, 11(4), 264. https://doi.org/10.3390/gels11040264

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop