What are the impacts of gamma irradiation on the sterilization of polymeric mats containing natural extracts?

ABSTRACT

In this study, electrospun polycaprolactone (PCL) mats containing 10% Brazilian red propolis extract were developed and evaluated after exposure to gamma irradiation at 29.91 kGy. The objective was to assess whether irradiation affects the physicochemical properties, structural integrity, thermal behavior, and bioactive compound stability of the composite. A range of characterization techniques was employed, including scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). All measurements were performed in triplicate (n = 3) and expressed as mean ± standard error of the mean. SEM (100 measurements) revealed that the morphology of the nanofibers remained preserved, with diameters of 1173 ± 360 nm (non-irradiated) and 1182 ± 340 nm (irradiated). FTIR results confirmed the chemical stability of PCL. Crystallinity increased from 52.7 ± 1.2% to 85.8 ± 2.5%, and DSC/TGA showed no change in degradation profile. Flavonoid content (15.4 ± 0.3 vs. 15.0 ± 0.4 mg QE/g) and antioxidant activity were maintained. These findings confirm that gamma irradiation preserves both structure and functionality, supporting its use in sterilizable biomaterials based on natural products.

Keywords:
Electrospun; Polycaprolactone; Brazilian red propolis

1. INTRODUCTION

Polycaprolactone (PCL) stands out as a biocompatible, biodegradable, and FDA-approved polymer with remarkable potential for various biomedical applications, including tissue engineering scaffolds, wound dressings, skin substitutes, and other applications [¹,²,³,⁴].

In recent years, Brazilian red propolis has emerged as a highly promising natural resource, particularly abundant in northeastern Brazil, owing to its rich and diverse composition of flavonoids, phenolics, and isoflavonoids [⁵,⁶,⁷]. These compounds exhibit demonstrated anti-inflammatory, antibacterial, and antioxidant activities both in vitro and in vivo, driving considerable interest for incorporation into biomedical materials [⁵, ⁶, ⁸,⁹,¹⁰,¹¹]. However, the therapeutic potential of red propolis critically depends on maintaining the integrity of its bioactive constituents, which can be compromised by conventional sterilization and processing methods [⁵, ⁷, ¹⁰]. The integration of red propolis extract into PCL matrices to create composite biomaterials offers a novel strategy to combine structural support with bioactive functionality [¹²]. Yet, sterilization, an indispensable step for clinical translation, poses a risk to the chemical stability of incorporated natural extracts. Gamma irradiation is widely recognized as an effective, low-temperature sterilization technique capable of inactivating pathogens without direct heat exposure. According to ISO guidelines, the irradiation dose must be rigorously optimized to ensure microbial safety while preserving the biological efficacy of sensitive compounds [¹³,¹⁴,¹⁵]. Although prior reports indicated that a 29 kGy dose does not significantly alter the morphology of electrospun PCL fibers, the impact of this sterilization protocol on the chemical integrity and bioactivity of red propolis remains underexplored [¹]. Assessing whether gamma irradiation triggers degradation of key flavonoids or diminishes antioxidant capacity is essential for advancing these composites toward clinical applications.

Therefore, the present study aims to systematically investigate the effects of 29 kGy gamma irradiation on PCL electrospun mats loaded with Brazilian red propolis extract. Specifically, we will examine changes in the chemical structure of propolis constituents, quantify flavonoid content and antioxidant activity, and evaluate morphology, crystallinity, and thermal behavior. By demonstrating the preservation of bioactive properties post-irradiation, this work seeks to establish a robust foundation for the development of sterilizable, bioactive polymeric scaffolds for wound healing and tissue engineering applications.

2. MATERIAIS E MÉTODOS

2.1. Materials and reagents

PCL (Mw ~ 80,000 g/mol), propolis extract, chloroform, methyl alcohol, ethyl alcohol, aluminum chloride, gallic acid, Folin-Ciocalteu reagent, and quercetin standard. All reagents were of analytical grade.

2.2. Process of obtaining the concentrated red propolis extract

The raw red propolis sample was obtained from the Paripueira apiary (Maceió, Brazil), whose geographical location is at a south latitude of 9º 26.448´, west longitude of 35º 31.710´, and altitude of 4.7 meters. To obtain the concentrated red propolis extract, 80% ethanol was used as the extraction liquid in the proportion of 400 mL to 100 g of the raw red propolis sample. The suspension was left to rest for 48 hours at room temperature (27 ºC), after which the supernatant was removed, and the procedure was repeated three times. The hydroalcoholic extract obtained was filtered through ordinary filter paper and roto evaporated (IKA® RV10, Germany) at 50 ºC [¹⁶].

2.3. Formation of PCL/Red propolis mats

The samples were prepared utilizing 10% dry red propolis extract relative to the total weight (1.8 g) of PCL [¹⁷]. The materials were dissolved in a standardized chloroform/methanol solution (20 mL) in a 4:1 v/v ratio. The solution was stirred at 27°C for 5 hours to ensure complete homogenization of the reagents.

The electrospinning technique produced the mats, applying a voltage of of 18 kV. A 10 mL glass syringe fitted with a 0.8 mm needle was used to load the polymer solution, and the distance between the rotating collector and the needle was maintained at 12 cm. The flow rate was controlled by gravitational force.

2.4. Exposure to gamma irradiation

Polycaprolactone (PCL) mats with red propolis extract were sterilized by gamma irradiation in a Multipurpose Cobalt-60 Irradiator with an accumulated dose of 29.91 kGy. The experiment was conducted at CETER, IPEN, São Paulo.

2.5. Extraction of the irradiated extract

Polycaprolactone (PCL) mats containing 10% w/w by weight red propolis extract, both irradiated and non-irradiated, were prepared as follows (Figure 1). Samples from each mat type were cut, accurately weighed, and placed in tubes containing fixed ethanol volume (8 mL). After 24 hours of incubation, the ethanol was decanted for subsequent characterization of the bioactive compounds. It is important to note that ethanol served solely as a solvent for the red propolis extract while the integrity of the PCL mat remained intact.

Figure 1
Schematic illustration of the solubilization of the red propolis extract contained in the electrospun mat for both irradiated and non-irradiated samples.

2.6. Quantification of flavonoids

A quercetin calibration curve was constructed by preparing a standard quercetin solution (200 μg/mL). Briefly, 0.05 g of quercetin was dissolved in 50 mL of ethanol under mild heating and agitation. After cooling, the solution was transferred to a 250 mL volumetric flask containing 150 mL of absolute ethanol and then diluted to volume at approximately 16 °C. A 5% aluminum chloride (AlCl₃) solution was prepared by dissolving 12.5 g of AlCl₃ in 200 mL of absolute ethanol and diluting it to 250 mL. For the calibration curve, test tubes were prepared with 1 mL of the 5% AlCl₃ solution, varying volumes of the quercetin standard, and absolute ethanol to reach a final volume of 10 mL (see Table 1 for specific concentrations). After 30 minutes, absorbance was measured at 425 nm using a UV-Vis spectrophotometer [¹⁸–²¹].

Table 1
Experimental values of the diffraction angle (2θ), full width at half maximum (FWHM), and interplanar spacing (d-spacing) for the (110) plane of PCL in PCL/Red Propolis Mats.

SAMPLE	2θ (°)	FHWM (°2θ)	D (110) (nm)
Non-irradiated	21.5	0.42	0.41
Irradiated	21.7	0.37	0.41

For the sample analysis, 0.1 g of dried extract was dissolved in 10 mL of absolute ethanol to prepare the ethanolic extract. A 4 mL aliquot of this extract was mixed with 6 mL of absolute ethanol and 1 mL of the 5% AlCl₃ solution. After a 30-minute incubation, absorbance was measured at 425 nm. The total flavonoid content was determined using the calibration curve and expressed as milligrams of quercetin equivalent per gram of sample (mg QE/g) and as a percentage (m/m). As a control, red propolis extract recovered from non-irradiated mats was used for comparison against irradiated samples [¹⁸,¹⁹,²⁰,²¹].

2.7. Determination of antioxidant capacity

The antioxidant capacity was assessed by a modified DPPH (2,2-diphenyl-1-picrylhydrazyl) reduction assay. A 0.1 mM DPPH solution was prepared by dissolving 0.0039 g of DPPH in 3 mL of absolute ethanol, followed by dilution to 100 mL with absolute ethanol. 0.1 g of dried extract was dissolved in 10 mL of absolute ethanol for the extract solution. Aliquots (5, 15, 30, 60, 180, and 400 μL) of this stock solution were transferred into separate 5 mL volumetric flasks. In each flask, 2 mL of the DPPH solution was added, and the volume was adjusted with absolute ethanol to achieve final concentrations of 1, 3, 6, 12, 36, and 80 μg/mL. Absorbance was recorded at 520 nm after sample preparation. The antioxidant activity was calculated using the Equation 1:

(1) $$\text{\% Antioxidant Activity = 100 –}\left[\left(\text{A\_sample – A\_blank}\right)\text{× 100}\right)\text{/A\_control]}$$

Here, A_sample is the absorbance of the DPPH solution with the extract, A_blank is the absorbance of the extract solution without DPPH, and A_control is the absorbance of the DPPH solution with ethanol [¹⁸, ²⁰].

2.8. Instrumentation

Scanning electron microscopy (SEM) analysis determined the membranes’ morphology before and after gamma irradiation. The membranes were carefully sectioned to an approximate size of 3 mm in length and 0.5 mm in width and mounted on an SEM sample holder. Before examination, each sample was coated with platinum using a Quorum evaporator, model Q150T E. An environmental scanning electron microscope from Zeiss, model EVO LS15 was used to analyze the samples (UNESP/FEIS). The free software ImageJ was employed to construct the histogram, with 100 fiber diameters measurements obtained from SEM analyses.

FTIR analysis was performed before and after gamma irradiation to assess changes in the surface functional groups during the process. The FTIR spectra were obtained using a Perkin Elmer Spectro 400 spectrometer, and data were collected over a range of 4000–600 cm−1.

X-ray diffraction (XRD) analysis was performed to understand the changes in crystallinity and structure of the PCL membranes with the bioactive before and after gamma irradiation. The XRD was recorded in the 2h range from 15 to 30 using a Bruker D8-Advance model (Germany), CuKa radiation, whose energy was 8.04 keV and wavelength of 1.54 Aÿ. The applied voltage was 40 kV and the current was 25 mA.

Differential Scanning Calorimetry (DSC) and Thermogravimetric Analysis (TGA) measurements were performed using a simultaneous thermal analyzer (model SDT, TA Instruments). Approximately 2.0 mg of sample was used under a nitrogen atmosphere with with a 100 mL/min flow rate and a heating rate of 10 °C/min, employing an open aluminum pan. The temperature range was set from 30 to 120 °C for DSC and 30 to 600 °C for TGA.

Crystallinity was calculated using the DSC results, following the Equation 2 [²¹]:

(2) $$\text{Crystallinity}\left(\text{\%}\right)\text{=}\left({\text{ΔH}}_{\text{x}}\text{× 100}\right)\text{/}\left({\text{ΔH}}_{\text{0}}\text{× F\_w}\right)$$

Where ΔH_x is the fusion enthalpy of the mats, ΔH₀ is the fusion enthalpy for 100% crystalline PCL (136 J/g, according to Qiu et al., 2005), and F_w is the fraction of polymer present in the mat.

All analyses were conducted in collaboration with the Chemical Catalysis and Reactivity Group (GCaR) – IQB, UFAL.

2.8. Statistical analysis

All measurements were performed in triplicate (n = 3). Results were expressed as mean ± standard error of the mean, based on descriptive statistical analysis.

3. RESULTS AND DISCUSSION

3.1. Scanning electron microscopy (SEM)

The scanning electron microscopy (SEM) analyses, performed in triplicate (n = 3), evaluated both irradiated and non-irradiated PCL mats containing 10% w/w red propolis extract (Figure 2). The fiber diameter distributions, determined from histogram analyses of 100 measurements, revealed that the non-irradiated samples exhibited a mean diameter of 1173 ± 360 nm, while the irradiated fibers had a mean diameter of 1182 ± 340 nm. The SEM images indicate that the surface morphology of the irradiated fibers—compared to the non-irradiated ones—showed no significant changes in roughness, fiber breakage, increased interconnections, or any other defects that might have resulted from the energy input during irradiation. These findings demonstrate that, at this scale, gamma irradiation does not alter the morphology of PCL mats containing red propolis extract.

Figure 2
SEM images and nanofiber diameter distributions of non-irradiated and irradiated samples of PCL/Red Propolis Mats samples. The non-irradiated fibers had a mean diameter of 1173 ± 360 nm, while the irradiated fibers had a mean diameter of 1182 ± 340 nm.

3.2. X-ray diffraction (XRD)

X-ray diffraction (XRD) analysis revealed diffraction peaks characteristic of polycaprolactone (PCL) at 2θ = 21.5–21.7° and 23.75°, corresponding to the (110) and (200) planes of the orthorhombic crystalline phase. These results confirm the preservation of the PCL crystalline structure in all samples, regardless of treatment or additive incorporation, as summarized in Table 1 and illustrated in Figure 3.

Figure 3
Experimental XRD patterns for PCL/Red Propolis Mats non-irradiated and irradiated.

Gamma irradiation resulted in subtle yet measurable modifications in the full width at half maximum (FWHM) of the X-ray diffraction peaks of the PCL/Red Propolis Mats. An average FWHM of 0.42° was observed in the non-irradiated samples, while the irradiated samples exhibited a reduced FWHM of 0.37°. This reduction in FWHM indicates a modest enhancement in crystalline order, likely due to a reorganization of the polymer chains induced by the irradiation process [²², ²³]. The slight narrowing of the diffraction peaks suggests that gamma irradiation can increase the crystallinity of the composite mats, which may have positive implications for their mechanical and thermal properties. Nonetheless, as summarized in Table 1, the overall effect on crystallinity is relatively minor, confirming that the fundamental structure of the PCL matrix is largely maintained following irradiation.

3.3. Thermal analysis

The thermal stability of the PCL/Red Propolis electrospun mats, before and after gamma irradiation, was evaluated by thermogravimetric analysis (TGA) and its derivative thermogravimetry (DTG), within the temperature range of 50 to 600 °C (Figures 4 and 5). The TGA curves (Figure 4) revealed that both non-irradiated and irradiated samples exhibited highly similar thermal decomposition profiles, predominantly characterized by a significant decomposition event between. This major mass loss event can be primarily attributed to the thermal degradation of the polycaprolactone (PCL) polymer matrix.

Figure 4
TGA analysis for PCL/Red Propolis Mats non-irradiated and irradiated.

Figure 5
Derivative Thermogravimetry (DTG) analysis for PCL/Red Propolis Mats non-irradiated and irradiated.

A detailed analysis of the DTG curves (Figure 5) highlighted a distinct decomposition peak centered around 400 °C, consistent with typical degradation temperatures previously reported for PCL-based materials [¹⁷]. Notably, the DTG profiles of irradiated samples closely matched those of the non-irradiated mats, with overlapping thermal degradation behavior and no evidence of additional peaks or shifts. These findings indicate that gamma irradiation at the applied dose (29.91 kGy) does not alter the thermal stability or the degradation profile of the PCL mats containing red propolis. Therefore, gamma irradiation emerges as an effective sterilization method that maintains the essential thermal characteristics and structural integrity required for biomedical applications of PCL/red propolis composite materials.

Differential scanning calorimetry (DSC) analysis was essential to understand the thermal transitions and crystallinity of the PCL polymer. As shown in Figure 6, the samples exhibited a consistent melting peak at 62.1 °C, indicating that although the melting behavior did not changes differences in crystalline organization of PCL occurred due to the introduced modifications. While the melting peak remained around 62.1 °C for both samples, the fusion enthalpies (ΔHf) and crystallinity indices (X%) displayed notable differences. The analysis of ΔHf, which quantifies the energy involved in the fusion process, revealed that the irradiated samples exhibited a significant increase in fusion enthalpy, suggesting increased crystallinity in the treated samples. Table 2 summarizes the ΔHf values and crystallinity percentages (X%) for each sample, highlighting the differences in crystalline properties.

Figure 6
DSC analysis for PCL/Red Propolis Mats non-irradiated and irradiated.

Table 2
DSC analysis results for non-irradiated and irradiated PCL/Red Propolis Mats.

	MASS LOSS (wt.%)
SAMPLE	ΔHf (EXP.) (J/g)	w	X (%)
Non-irradiated	64.5	0.9	52.7 ± 1.2
Irradiated	111.0	0.9	85.8 ± 2.5

The DSC analysis revealed that the non-irradiated sample exhibited 52.7 ± 1.2% crystallinity, whereas the sample subjected to gamma irradiation achieved 85.8 ± 2.5% crystallinity (Table 2). Consistently, the XRD data corroborated this increase by showing a reduction in the full width at half maximum (FWHM) of the diffraction peaks in the irradiated sample, reflecting a higher degree of crystalline order. These findings suggest that gamma irradiation promotes a reorganization of the polymer chains, leading to more efficient molecular packing and a substantial crystallinity enhancement.

Conceptually, this increase in crystallinity can be attributed to the energy imparted by gamma irradiation, which reduces internal stresses and facilitates the transformation of amorphous regions into more ordered crystalline zones. The resulting molecular reorganization not only improves the homogeneity of intermolecular interactions but may also promote the growth of larger crystalline domains at the expense of less ordered regions. This structural refinement is critical, as higher crystallinity is often associated with enhanced mechanical strength, stiffness, and thermal stability—properties that are particularly important for the performance of biomaterials.

These observations, which agree with previous reports [²⁴], underscore the potential of controlled gamma irradiation as a tool for tailoring the microstructural and macroscopic properties of polymeric scaffolds. Modifications in the crystalline structure could be highly advantageous for applications requiring materials with superior durability and resistance to thermal degradation.

3.4. Fourier Transform Infrared spectroscopy (FTIR)

The Fourier Transform Infrared (FTIR) spectrum, illustrated in Figure 7, provides critical insights into the chemical interactions and functional groups present in PCL/Red Propolis Mats.

Figure 7
FTIR spectrum of non-irradiated and irradiated PCL/Red Propolis Mats; red arrows indicate absorption bands characteristic of red propolis, while black arrows denote bands associated with PCL.

In the PCL/Red Propolis Mats, distinct vibrational bands corresponding to the red propolis extract were observed. Notably, absorption in the 3600–3000 cm−1 range is attributed to the extract’s O–H stretching of phenolic groups. Two additional bands at 2971 and 2932 cm−1, corresponding to the symmetric and asymmetric stretching vibrations of CH₂ and CH₃ groups, respectively, were also identified; these bands overlap with the 2944 cm−1 band associated with the same vibrational mode in PCL. Moreover, peaks at 1619 and 1457 cm−1 are related to the C=C stretching in the aromatic rings of flavonoids. It is well established that phenolic and flavonoid compounds generate stretching and bending vibrations within the narrow 1300–1000 cm−1 region, as evidenced by the band at 1109 cm−1 (δC–OH), while the absorption at 840 cm−1 is assigned to out-of-plane bending (γCH) [⁶, ¹⁸, ¹⁹].

Regarding the PCL component, characteristic bands were observed at 2944 and 2862 cm−1 (CH₂ stretching), at 1724 cm−1 (C=O stretching), at 1365 cm−1 (CH₂ bending), at 1294 cm−1 (C–O and C–C stretching), at 1240 cm−1 (asymmetric COC stretching), at 1166 cm−1 (symmetric C–O and C–C stretching), and at 1045 and 959 cm−1 (CH₂ bending). Notably,, no new bands appeared, nor were any bands lost, after gamma irradiation, confirming that the irradiation process did not alter the material’s chemical structure [²⁵, ²⁶].

3.5. Evaluation of bioactive compound degradation

Figure 8 presents the quantification of flavonoids in the red propolis extract recovered from the PCL mats before and after gamma irradiation.

Figure 8
Flavonoid quantification in the extract recovered from PCL/Red Propolis Mats membranes before and after exposure to gamma radiation.

Based on the bar chart, the non-irradiated sample exhibited a flavonoid content of approximately 1.53% (15.4 ± 0.3 mg QE/g), whereas the irradiated sample showed about 1.49% (15.0 ± 0.4 mg QE/g) (Figure 8). Quantification was performed in triplicate (n = 3), and expressed as mean ± standard error of the mean, based on descriptive statistical analysis. The minimal difference between these values suggests that gamma irradiation did not induce notable degradation of the flavonoid compounds in red propolis.

This stability can be attributed to the molecular structure of many flavonoids, which possess conjugated aromatic systems and hydroxyl groups capable of delocalizing the energy absorbed during irradiation [⁵, ⁸]. Such structural features may reduce the likelihood of fragmentation or oxidation under gamma exposure. Additionally, compounds such as vestitol, neovestitol, and medicarpin—commonly found in Brazilian red propolis—have been reported to exhibit considerable resistance to photodegradation and oxidative stress, which may contribute to the overall preservation of bioactivity [¹⁰, ²⁷, ²⁸].

Consequently, these findings support using gamma irradiation as an effective sterilization method for red propolis-based materials without compromising their bioactive properties. This preservation of flavonoid content is critical in biomedical and pharmaceutical applications, where the antioxidant and anti-inflammatory activities associated with these compounds are critical for therapeutic efficacy.

Based on the antioxidant activity curves (Figure 9), which represent the mean of triplicate measurements (n = 3), the irradiated sample exhibits a profile nearly identical to the non-irradiated sample across the evaluated concentration range. This observation indicates that gamma irradiation did not significantly diminish the antioxidant capacity of the propolis extract, suggesting that the bioactive compounds remained chemically stable after exposure. Red propolis from Alagoas is known to be rich in phenolic and flavonoid constituents—including isoflavones, pterocarpans (e.g., medicarpin), neoflavonoids, chalcones, vestitol, and neovestitol—that collectively confer robust free radical scavenging properties [⁶, ¹⁹, ²⁹,³⁰,³¹,³²]. The retention of these compounds post-irradiation supports the development of sterilizable, antioxidant biomaterials incorporating natural bioactives.

Figure 9
Antioxidant activity of red propolis extract recovered from PCL/Red Propolis mats before and after gamma irradiation. Data represent the mean values of triplicate measurements (n = 3) across the evaluated concentration range.

4. CONCLUSION

This study successfully developed and characterized polycaprolactone (PCL) electrospun mats incorporating red propolis extract, evaluating their physicochemical properties before and after gamma irradiation at 29.91 kGy. The morphological analyses via scanning electron microscopy (SEM) demonstrated that the fiber structure remained intact following irradiation, with no significant changes in roughness, fiber breakage, or diameter distribution (1173 ± 360 nm vs. 1182 ± 340 nm, based on descriptive statistical analysis). Fourier-transform infrared spectroscopy (FTIR) confirmed the presence of characteristic absorption bands of both PCL and red propolis, without evidence of new bond formation or degradation. At the same time, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) revealed a clear increase in crystallinity (52.7 ± 1.2% to 85.8 ± 2.5%), likely due to polymer chain reorganization.

Regarding bioactive compound stability, flavonoid quantification demonstrated minimal degradation post-irradiation, with values of 15.4 ± 0.3 mg QE/g and 15.0 ± 0.4 mg QE/g for non-irradiated and irradiated samples, respectively. Likewise, the antioxidant activity of the red propolis extract remained nearly unchanged across the tested concentration range, indicating preservation of its radical-scavenging capacity. These findings underscore the robustness of red propolis as a source of bioactive molecules, even after exposure to sterilization procedures.

Additionally, the evaluation of thermal stability via thermogravimetric analysis (TGA) and derivative thermogravimetry (DTG) confirmed that the mats exhibited a decomposition profile characteristic of PCL, with minor deviations attributable to propolis. These findings further indicate that gamma irradiation did not adversely affect the structural integrity of the composite material.

Overall, the results demonstrate that PCL mats containing red propolis retain both their structural and functional properties after sterilization. This is especially important in the field of natural products, where degradation of bioactive compounds during processing may compromise the therapeutic potential of the final product—making the incorporation of such extracts ineffective. Thus, this study contributes to the development of sterilizable bioactive systems and reinforces the applicability of red propolis in biomaterial design.

5. ACKNOWLEDGEMENTS

The authors gratefully acknowledge the financial support provided by CNPq (grant numbers 429027/2018-4 and 305893/2022-0) and FAPEAL (grant number E:60030.0000001210/2024). Additionally, we express our gratitude to UFAL, UNESP, IPEN, and IFAL for providing the necessary research infrastructure, as well as to Professor Mario R. Meneghetti (UFAL) from the GCAR Group for his valuable contributions to the analyses.

6. BIBLIOGRAPHY

• ^[1] JOSEPH, B., AUGUSTINE, R., KALARIKKAL, N., et al., “Recent advances in electrospun polycaprolactone based scaffolds for wound healing and skin bioengineering applications”, Materials Today. Communications, v. 19, pp. 319–335, Jun. 2019. doi: http://doi.org/10.1016/j.mtcomm.2019.02.009.
  » https://doi.org/10.1016/j.mtcomm.2019.02.009
• ^[2] MOKHENA, T., CHABALALA, M., MAPUKATA, S., et al., “Electrospun PCL‐based materials for health‐care applications: an overview”, Macromolecular Materials and Engineering, v. 308, n. 8, pp. 2300388, 2024. doi: http://doi.org/10.1002/mame.202300388.
  » https://doi.org/10.1002/mame.202300388
• ^[3] MANCIPE, J.M.A., DIAS, M.L., THIRÉ, R.M. S.M., “Morphological evaluation of electrospun polycaprolactone fibers depending on the type of solvent”, Revista Materia, v. 24, n. 3, e12400, 2019. doi: http://doi.org/10.1590/S1517-707620190003.0713.
  » https://doi.org/10.1590/S1517-707620190003.0713
• ^[4] THANGAVEL, S., KANDASAMY, K.T., RATHANASAMY, R., et al., “Enhancing thermal and mechanical properties of polycaprolactone nanofibers with graphene and graphene oxide reinforcement for bio-medical applications”, Matéria, v. 29, n. 3, e20240324, 2024. doi: http://doi.org/10.1590/1517-7076-rmat-2024-0324.
  » https://doi.org/10.1590/1517-7076-rmat-2024-0324
• ^[5] ALDANA-MEJÍA, J.A., CCANA-CCAPATINTA, G.V., SQUARISI, I.S., et al., “Nonclinical toxicological studies of Brazilian red propolis and its primary botanical source Dalbergiaecastaphyllum”, Chemical Research in Toxicology, v. 34, n. 4, pp. 1024–1033, 2021. doi: http://doi.org/10.1021/acs.chemrestox. 0c00356. PubMed PMID: 33720704.
  » https://doi.org/10.1021/acs.chemrestox.0c00356
• ^[6] NASCIMENTO, T.G., SILVA, A.S., LESSA CONSTANT, P.B., et al., “Examen de las actividades fitoquímica, antioxidante y antibacteriana de extractos comerciales de propóleos”, Journal of Apicultural Research, v. 57, n. 2, pp. 246–254, Mar. 2018. doi: http://doi.org/10.1080/00218839.2017.1412563.
  » https://doi.org/10.1080/00218839.2017.1412563
• ^[7] RUFATTO, L., LUCHTENBERG, P., GARCIA, C., et al., “Brazilian red propolis: chemical composition and antibacterial activity determined using bioguided fractionation”, Microbiological Research, v. 214, pp. 74–82, 2018. doi: http://doi.org/10.1016/j.micres.2018.05.003. PubMed PMID: 30031483.
  » https://doi.org/10.1016/j.micres.2018.05.003
• ^[8] BUENO-SILVA, B., ALENCAR, S.M., KOO, H., et al., “Anti-inflammatory and antimicrobial evaluation of neovestitol and vestitol isolated from Brazilian red propolis”, Journal of Agricultural and Food Chemistry, v. 61, n. 19, pp. 4546–4550, 2013. doi: http://doi.org/10.1021/jf305468f. PubMed PMID: 23607483.
  » https://doi.org/10.1021/jf305468f
• ^[9] BUENO-SILVA, B., KAWAMOTO, D., ANDO-SUGUIMOTO, E.S., et al., “Brazilian red propolis effects on peritoneal macrophage activity: nitric oxide, cell viability, pro-inflammatory cytokines and gene expression”, Journal of Ethnopharmacology, v. 207, pp. 100–107, Jul. 2017. doi: http://doi.org/10.1016/j.jep.2017.06.015. PubMed PMID: 28624363.
  » https://doi.org/10.1016/j.jep.2017.06.015
• ^[10] FRANCHIN, M., CÓLON, D.F., CASTANHEIRA, F.V.S., et al., “Vestitol isolated from brazilian red propolis inhibits neutrophils migration in the inflammatory process: elucidation of the mechanism of action”, Journal of Natural Products, v. 79, n. 4, pp. 954–960, Apr. 2016. doi: http://doi.org/10.1021/acs.jnatprod.5b00938. PubMed PMID: 26938776.
  » https://doi.org/10.1021/acs.jnatprod.5b00938
• ^[11] SHEHATA, M.G., AHMAD, F.T., BADR, A.N., et al., “Chemical analysis, antioxidant, cytotoxic and antimicrobial properties of propolis from different geographic regions”, Annals of Agricultural Science, v. 65, n. 2, pp. 209–217, Dec. 2020. doi: http://doi.org/10.1016/j.aoas.2020.12.001.
  » https://doi.org/10.1016/j.aoas.2020.12.001
• ^[12] RAMOS, S.D., BERNARDO, L.R., BÜRCK, M., et al., “Propolis extract: weaving antioxidant power into polymeric composites through electrospinning”, Polymers, v. 16, n. 22, pp. 3230, Nov. 2024. doi: http://doi.org/10.3390/polym16223230. PubMed PMID: 39599321.
  » https://doi.org/10.3390/polym16223230
• ^[13] DE CASSAN, D., HOHEISEL, A.L., GLASMACHER, B., et al., “Impact of sterilization by electron beam, gamma radiation and X-rays on electrospun poly-(ε-caprolactone) fiber mats”, Journal of Materials Science. Materials in Medicine, v. 30, n. 4, pp. 42, Apr. 2019. doi: http://doi.org/10.1007/s10856-019-6245-7. PubMed PMID: 30919082.
  » https://doi.org/10.1007/s10856-019-6245-7
• ^[14] PREEM, L., VAARMETS, E., MEOS, A., et al., “Effects and efficacy of different sterilization and disinfection methods on electrospun drug delivery systems”, International Journal of Pharmaceutics, v. 567, pp. 118450, 2019. doi: http://doi.org/10.1016/j.ijpharm.2019.118450. PubMed PMID: 31229531.
  » https://doi.org/10.1016/j.ijpharm.2019.118450
• ^[15] HANSEN, J.M., FIDOPIASTIS, N., BRYANS, T., et al., “Radiation sterilization: dose is dose”, Biomedical Instrumentation & Technology, v. 54, n. s1, pp. 45–52, 2020. doi: http://doi.org/10.2345/0899-8205-54.s3.45. PubMed PMID: 34169974.
  » https://doi.org/10.2345/0899-8205-54.s3.45
• ^[16] NASCIMENTO, T.G., DA SILVA, P.F., AZEVEDO, L.F., et al., “Polymeric nanoparticles of Brazilian red propolis extract: preparation, characterization, antioxidant and leishmanicidal activity”, Nanoscale Research Letters, v. 11, n. 1, pp. 301, Dec. 2016. doi: http://doi.org/10.1186/s11671-016-1517-3. PubMed PMID: 27316742.
  » https://doi.org/10.1186/s11671-016-1517-3
• ^[17] COSTA, L.M.M., MATTOSO, L.H.C., FERREIRA, M., “Electrospinning of PCL/natural rubber blends”, Journal of Materials Science, v. 48, n. 24, pp. 8501–8508, Dec. 2013. doi: http://doi.org/10.1007/s10853-013-7667-0.
  » https://doi.org/10.1007/s10853-013-7667-0
• ^[18] SILVA, M.C., NASCIMENTO, I., RIBEIRO, V.S., et al., “Avaliação do método de obtenção de scaffolds quitosana/curcumina sobre a estrutura, morfologia e propriedades térmicas”, Matéria, v. 21, n. 3, pp. 560–568, Jul. 2016. doi: http://doi.org/10.1590/S1517-707620160003.0054.
  » https://doi.org/10.1590/S1517-707620160003.0054
• ^[19] ANDRADE, J.K.S., DENADAI, M., ANDRADE, G.R.S., et al., “Development and characterization of microencapsules containing spray dried powder obtained from Brazilian brown, green and red propolis”, Food Research International, v. 109, pp. 278–287, 2018. doi: http://doi.org/10.1016/j.foodres.2018.04.048. PubMed PMID: 29803451.
  » https://doi.org/10.1016/j.foodres.2018.04.048
• ^[20] SÁ, P.G.S., GUIMARÃES, A.L., OLIVEIRA, A.P., et al., “Fenóis totais, flavonoides totais e atividade antioxidante de Selaginellaconvoluta (Arn.) Spring (Selaginellaceae)”, Revista de CiênciasFarmacêuticasBásica e Aplicada, v. 33, n. 4, pp. 561–566, 2012.
• ^[21] DARGAVILLE, B.L., HUTMACHER, D.W., “A quest for revisiting analysis of polycaprolactone crystallinity”, Trends in Chemistry, v. 6, n. 1, pp. 5–13, Jan. 2024. doi: http://doi.org/10.1016/j.trechm. 2023.10.007.
  » https://doi.org/10.1016/j.trechm.2023.10.007
• ^[22] MANAS, D., OVSIK, M., MIZERA, A., et al., “The effect of irradiation on mechanical and thermal properties of selected types of polymers”, Polymers, v. 10, n. 2, pp. 158, Feb. 2018. doi: http://doi.org/10.3390/polym10020158. PubMed PMID: 30966194.
  » https://doi.org/10.3390/polym10020158
• ^[23] ROSENBERG, Y., SIEGMANN, A., NARKIS, M., et al., “Low dose γ‐irradiation of some fluoropolymers: effect of polymer chemical structure”, Journal of Applied Polymer Science, v. 45, n. 5, pp. 783–795, 1992. doi: http://doi.org/10.1002/app.1992.070450504.
  » https://doi.org/10.1002/app.1992.070450504
• ^[24] AUGUSTINE, R., SAHA, A., JAYACHANDRAN, V.P., et al., “Dose-dependent effects of gamma irradiation on the materials properties and cell proliferation of electrospun polycaprolactone tissue engineering scaffolds”, International Journal of Polymeric Materials, v. 64, n. 10, pp. 526–533, Oct. 2015. doi: http://doi.org/10.1080/00914037.2014.977900.
  » https://doi.org/10.1080/00914037.2014.977900
• ^[25] SHARIFI, F., ATYABI, S.M., NOROUZIAN, D., et al., “Polycaprolactone/carboxymethyl chitosan nanofibrous scaffolds for bone tissue engineering application”, International Journal of Biological Macromolecules, v. 115, pp. 243–248, 2018. doi: http://doi.org/10.1016/j.ijbiomac.2018.04.045. PubMed PMID: 29654862.
  » https://doi.org/10.1016/j.ijbiomac.2018.04.045
• ^[26] ELZEIN, T., NASSER-EDDINE, M., DELAITE, C., et al., “FTIR study of polycaprolactone chain organization at interfaces”, Journal of Colloid and Interface Science, v. 273, n. 2, pp. 381–387, May. 2004. doi: http://doi.org/10.1016/j.jcis.2004.02.001. PubMed PMID: 15082371.
  » https://doi.org/10.1016/j.jcis.2004.02.001
• ^[27] FREIRES, I.A., ALENCAR, S.M., ROSALEN, P.L., “A pharmacological perspective on the use of Brazilian Red Propolis and its isolated compounds against human diseases”, European Journal of Medicinal Chemistry, v. 110, pp. 267–279, 2016. doi: http://doi.org/10.1016/j.ejmech.2016.01.033. PubMed PMID: 26840367.
  » https://doi.org/10.1016/j.ejmech.2016.01.033
• ^[28] INUI, S., HATANO, A., YOSHINO, M., et al., “Identification of the phenolic compounds contributing to antibacterial activity in ethanol extracts of Brazilian red propolis”, Natural Product Research, v. 28, n. 16, pp. 1293–1296, Aug. 2014. doi: http://doi.org/10.1080/14786419.2014.898146. PubMed PMID: 24666260.
  » https://doi.org/10.1080/14786419.2014.898146
• ^[29] NASCIMENTO, T.G., SANTOS ARRUDA, R.E., CRUZ ALMEIDA, E.T., et al., “Comprehensive multivariate correlations between climatic effect, metabolite-profile, antioxidant capacity and antibacterial activity of Brazilian red propolis metabolites during seasonal study”, Scientific Reports, v. 9, n. 1, pp. 18293, 2019. doi: http://doi.org/10.1038/s41598-019-54591-3. PubMed PMID: 31797960.
  » https://doi.org/10.1038/s41598-019-54591-3
• ^[30] FERREIRA, L.M.M.C., MODESTO, Y.Y., SOUZA, P.D.Q., et al., “Characterization, biocompatibility and antioxidant activity of hydrogels containing propolis extract as an alternative treatment in wound healing”, Pharmaceuticals, v. 17, n. 5, pp. 575, 2024. doi: http://doi.org/10.3390/ph17050575. PubMed PMID: 38794145.
  » https://doi.org/10.3390/ph17050575
• ^[31] RUFATTO, L.C., LUCHTENBERG, P., GARCIA, C., et al., “Brazilian red propolis: chemical composition and antibacterial activity determined using bioguided fractionation”, Microbiological Research, v. 214, pp. 74–82, Sep. 2018. doi: http://doi.org/10.1016/j.micres.2018.05.003. PubMed PMID: 30031483.
  » https://doi.org/10.1016/j.micres.2018.05.003
• ^[32] DEVEQUI-NUNES, D., MACHADO, B.A.S., BARRETO, G.A., et al., “Chemical characterization and biological activity of six different extracts of propolis through conventional methods and supercritical extraction”, PLoS One, v. 13, n. 12, e0207676, 2018. doi: http://doi.org/10.1371/journal.pone.0207676. PubMed PMID: 30513100.
  » https://doi.org/10.1371/journal.pone.0207676

Publication Dates

• Publication in this collection
  05 Sept 2025
• Date of issue
  2025

History

• Received
  30 Mar 2025
• Accepted
  28 July 2025