Method Article

Development and Characterization of Fusidic Acid-Loaded Alginate-Aloe vera Based Hydrogel Film

1.8K views

⸱

DOI:

10.3791/67068

⸱

December 13th, 2024

 ,  ,  ,  ,  ,  ,  ,  ,  ,  , 
1Faculty of Pharmacy, MAHSA University, 2Radiopharmaceutical Technology Group, Medical Technology Division, Malaysia Nuclear Agency, 3Faculty of Pharmacy, Department of Pharmaceutical Sciences, Aqaba University of Technology, 4Department of Parasitology and Medical Entomology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 5Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, 6Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, 7Department of Zoology, College of Science, King Saud University, 8Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, 9Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, 10Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 11Faculty of Pharmacy, University College of MAIWP International

In This Article

Summary

A formulation of fusidic acid-loaded hydrogel film was developed with different Aloe vera ratios and characterized in this study.

Abstract

A new fusidic acid-loaded hydrogel film was prepared via the solvent casting technique using alginate and Aloe vera. The hydrogel films were optimized using different ratios of sodium alginate, Aloe vera, and glycerin. The films containing 10% glycerin (w/w of alginate) exhibited the best appearance. Incorporating Aloe vera influenced the thickness, swelling behavior, water vapor permeability, and drug release profile of the hydrogel films. Higher Aloe vera content resulted in thicker films (up to a certain ratio), increased swelling, reduced water vapor permeability, and a prolonged drug release of up to 93% over 12 h. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of key functional groups and the interaction between the hydrogel components. The study suggests that the combination of sodium alginate, Aloe vera, and glycerin can improve the mechanical properties and drug release profiles of hydrogel films, making them a promising option for enhanced topical drug delivery and wound healing applications.

Introduction

Fusidic acid is a potent steroidal antibiotic derived from Fusidium coccineum. It is widely used to treat staphylococcal skin infections and impetigo. This drug has high efficacy, even against antibiotic-resistant strains, and low toxicity, making it a suitable option for managing skin infections1. Unlike other topical antibiotics, fusidic acid penetrates deeply into the skin, enhancing its antimicrobial effects, especially in areas where the skin's protective barrier is damaged. Its structure allows for versatile solubility characteristics, enabling widespread distribution throughout body tissues, which is further enhanced in its sodium fusidate form for better water solubility and penetration rates2,3. Fusidic acid can be administered in various ways, including orally, intravenously, and topically, adapting to different treatment needs and making it a flexible choice for various infections4.

Hydrogels, with their high water content and biocompatibility, have emerged as innovative carriers for antibiotics in wound treatment, providing moisture retention, controlled drug release, and improved patient outcomes. They are made from natural or synthetic polymers like alginate, which is favored for its strong biocompatibility, affordability, and gelation properties that mimic natural tissue extracellular matrices5. Alginate-based hydrogels, in particular, offer a moist environment conducive to wound healing, do not adhere to the wound, and allow for easy removal, making them ideal for delivering bioactive substances and supporting tissue regeneration. The development of hydrogels encapsulating antibiotics represents a significant advancement in wound care, ensuring targeted drug delivery and sustained therapeutic effects6,7.

The proposed fusidic acid-loaded alginate/Aloe vera hydrogel aims to overcome fusidic acid's solubility challenges and enhance its dermal penetration. Aloe vera, known for its skin-friendly, moisturizing, and antibacterial properties, also serves as a chemical penetration enhancer, potentially improving the efficacy of fusidic acid in treating skin infections8,9. This innovative formulation leverages the synergistic effects of Aloe vera and alginate hydrogel to create a conducive healing environment, optimize drug delivery, and offer a promising solution for enhanced treatment of skin infections, making the most of fusidic acid's potent antimicrobial activity with improved delivery and healing outcomes10.

Protocol

The details of the reagents and equipment used in this study are listed in the Table of Materials.

1. Preparation of fusidic acid hydrogel films

  1. Prepare solutions of sodium alginate (2.0% w/v) and Aloe vera (1.0% w/v) by dissolving them in distilled water.
  2. Add 200 mg of fusidic acid to the sodium alginate solution and stir for 1 h.
  3. Add glycerol to the alginate solution at concentrations of 10%, 12%, and 14% (w/w, based on the alginate mass).
  4. Combine the alginate and Aloe vera solutions to achieve final alginate/Aloe vera ratios (v/v) of 100:0, 90:10, 80:20, and 75:25.
  5. Cast 25 mL of each mixture into glass Petri dishes (100 mm x 20 mm) and leave to dry at room temperature (25 °C) and controlled humidity (50%) for 2 days.
  6. Immerse the dried films into a calcium chloride (CaCl2) aqueous solution (5.0% w/v) for 5 min to obtain the hydrogel films.
  7. Wash the resulting films with distilled water and dry them at room temperature before use.

2. Determining the film thickness

  1. Use a digital micrometer to measure the thickness of the film11.
  2. Take measurements at five distinct points across the film.
  3. Record the measurements obtained from each point.
  4. Calculate the average film thickness based on the measurements taken.

3. Determining the swelling index

  1. Cut the film samples into 2 cm x 2 cm squares using a lab knife.
  2. Weigh each sample accurately.
  3. Soak the samples in PBS buffer (pH 6.8) at room temperature for 24 h.
  4. Absorb any excess water on the film surface using filter paper.
  5. Weigh the samples again.
  6. Weigh the films at different time intervals. Calculate the swelling capacity using the following equation:
    Swelling percentage formula, Sw(%)=(Wh-Wd)/Wd x 100, used in material science equations.
    NOTE: Wh represents the hydrated weight of the sample, and Wd corresponds to the dry weight of the sample.

4. Water vapor permeability or occlusion test

  1. Cover the opening of a glass beaker containing 50 mL of water with filter paper11.
  2. Apply a film-forming solution to one of the papers and permit it to develop a film.
  3. Store the beaker at room temperature and humidity.
  4. Assess the film's permeability to water based on the decrease in water weight within the beaker.
  5. To determine the evaluation of water vapor permeability for the prepared hydrogel film, use the following formula:
    Percent error formula: F = ((A−B)X100)/A; equation for measurement accuracy.
    NOTE: The occlusivity factor, F, measures the permeability of a film. It is determined by calculating the difference in water weight between a glass beaker covered with filter paper without a film and a glass beaker covered with filter paper coated with the film. A smaller occlusivity factor value indicates greater film permeability.

5. Fourier transform infrared spectroscopy (FTIR)

  1. Place the hydrogel sample onto the ATR crystal of the FTIR spectroscopy machine.
  2. Set the wavenumber range to 4000-400 cm−1.
  3. Set the scan rate to 60 scans per sample.
  4. Set the resolution to 4 cm−1.
  5. Record an air background before each sample run.
  6. Run the analysis for each hydrogel sample individually.
  7. Analyze the FTIR spectra for each hydrogel sample to confirm functional groups and examine interactions among all components12.
  8. Repeat the analysis for raw Aloe vera, sodium alginate, glycerin, and fusidic acid separately.

6. Differential Scanning Calorimetry (DSC)

  1. Use a commercially available thermal analysis instrument to acquire thermal profiles.
  2. Craft the measurement samples from multiple circular pieces cut from the polymer film.
  3. Investigate the temperature range from 25-230 °C.
  4. Set the heating/cooling rate at 20 °C/min.
  5. Carry out temperature and enthalpy calibration using standard indium with compatible software.

7. Drug release test

  1. Prepare a solution of 50 mL PBS (pH = 7.4) as the dissolution medium.
  2. Immerse the hydrogel films in PBS at 37 °C for 24 h while stirring at a rate of 50 rpm.
  3. At predetermined intervals, collect 2 mL of the samples.
  4. Dilute and filter the collected samples through a syringe filter.
  5. Promptly replenish an equivalent volume of PBS.
  6. Assess the concentrations of fusidic acid released using a UV spectrophotometer, measuring absorption at 285 nm.
  7. Evaluate the release kinetics of fusidic acid using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models4.

Results

Preparation of alginate/Aloe vera hydrogel film
Different ratios of sodium alginate, Aloe vera, and glycerin were used to prepare the formulation of hydrogel film. The final preparation and assessment of the formulations were carried out only with 10% glycerin (w/w of alginate). Figure 1 shows the hydrogel film with different Aloe vera ratios. This selection was made because other glycerin ratios did not provide the necessary adhesiveness and flexibility, leading to improperly formed films. The strong adhesion and elasticity of the films were due to the presence of sodium alginate and glycerin. The addition of Aloe vera did not alter the appearance but affected the viscosity of the solutions during preparation.

Thickness
The thickness results are presented in Table 1. The control sample A, which contained only alginate, had a thickness of 0.11 mm. As the proportion of Aloe vera increased in samples B and C, the film thickness increased, measuring 0.13 mm and 0.12 mm, respectively. However, sample D, which had the highest proportion of Aloe vera, had the thinnest film at 0.09 mm. Based on these results, it appears that the addition of Aloe vera may have some effect on the film thickness to a certain extent.

Swelling index
Assessing the capacity of hydrogels to absorb various liquids is a key aspect of this research. The focus is on understanding the ability of polymers to swell under different conditions. As illustrated in Figure 2, the swelling index results over time reveal the influence of varying Aloe vera concentrations on the water absorption capacity of alginate-based films. The film with 0% Aloe vera (A) exhibited the lowest swelling index after 24 h (364.8%). In contrast, samples with increasing Aloe vera content showed progressively higher swelling indices, with the 25:75 film (D) reaching the highest value of approximately 549%. These results indicate that the hydrophilic properties of Aloe vera play a significant role in enhancing the swelling behavior of the films. Figure 3 shows the hydrogel film before and after swelling.

Water vapor permeability or occlusion test
The water vapor permeability of the films was assessed by comparing the amount of water in a beaker with and without the films. According to the results shown in Table 2, the control sample with no Aloe vera showed no occlusion effect, while the other samples exhibited an increase in the occlusivity factor upon the addition of Aloe vera. Sample B had an occlusivity factor of 13.2, while samples C and D had the highest occlusivity factor of 20. This indicates that the addition of Aloe vera helped decrease the water vapor permeability (WVP) of the alginate films.

Structural analysis by FTIR
Figure 4 demonstrates the FTIR spectra of hydrogel formulations containing fusidic acid, along with the spectra of raw materials, including sodium alginate, Aloe vera, glycerin, and fusidic acid. The spectra of the hydrogel formulation show a broad absorption band around 3200-3400 cm−1 and a band at approximately 1636 cm−1, which correspond to the stretching of O-H groups attributed to sodium alginate, Aloe vera, and glycerin, as well as the asymmetric stretching vibration of alginate COO groups, respectively13. Additionally, the absorption peak at around 1330-1340 cm−1 reflects the bending vibration of the C-H group, while the peak at 1171 cm−1 is related to the C-O stretching vibration of sodium alginate.

Differential Scanning Calorimetry (DSC)
Differential Scanning Calorimetry (DSC) was used to analyze the thermal behavior of sodium alginate, Aloe vera, pure fusidic acid, and drug-loaded hydrogel film. The thermogram of sodium alginate showed an endothermic peak at approximately 132 °C (as demonstrated in Figure 5). On the other hand, the Aloe vera thermogram displayed multiple peaks. The DSC analysis of pure fusidic acid showed a sharp and well-defined endothermic peak at 184.5 °C. For the drug-loaded hydrogel film, only a broad peak was detected between 103 °C and 170 °C, lacking any melting peaks for the components or the drug.

Drug release
The in vitro drug release was examined for all samples over 24 h using PBS solution at pH 7.4. The film samples showed a gradual release of the drug, likely due to the compact hydrogel structure. The samples containing Aloe vera displayed 89.7% to 93% of fusidic acid release within 12 h, while the control film with no Aloe vera released all of the drugs after 12 h, as shown in Figure 6. Different release kinetic models were evaluated for the fusidic acid. The results are presented in Table 3. The drug release results were best fitted with the zero-order release model, which exhibited the highest R2 values.

Polymer blend film comparison; 100:0, 90:10, 80:20, 75:25; material composition analysis.
Figure 1: Physical appearance of fusidic acid-loaded hydrogel films. Photographs of fusidic acid-loaded alginate/Aloe vera hydrogel films at various ratios: (A) 100:0, (B) 90:10, (C) 80:20, and (D) 75:25, observed under 4x magnification. Please click here to view a larger version of this figure.

Swelling index over time graph; polymers (0:100, 10:90, 20:80, 25:75) absorption analysis.
Figure 2: Swelling index of hydrogel films. The swelling index percentage of fusidic acid-loaded alginate/Aloe vera hydrogel films at different ratios: (A) 100:0, (B) 90:10, (C) 80:20, and (D) 75:25. The error bars represent standard deviation (SD), n = 3. Please click here to view a larger version of this figure.

Polymer film comparison; two samples labeled A and B; visual texture analysis.
Figure 3: Hydrogel film before and after swelling. Comparison of a hydrogel film (A) before and (B) after swelling, illustrating the changes in physical appearance due to the swelling process. Please click here to view a larger version of this figure.

FTIR spectra diagram; displays wavenumber absorption patterns for chemical analysis, spectral fitting.
Figure 4: FTIR spectrum analysis. FTIR spectra of various components and formulations: (A) fusidic acid, (B) sodium alginate, (C) Aloe vera, (D) glycerin, (E) formulation 100:0, (F) formulation 90:10, (G) formulation 80:20, and (H) formulation 75:25. Please click here to view a larger version of this figure.

Heat flow vs. temperature graph; DSC analysis of hydrogels, fusidic acid, aloe vera, alginate.
Figure 5: DSC Thermogram of hydrogel formulations. Differential scanning calorimetry (DSC) thermograms of the hydrogel formulation, fusidic acid, alginate, and Aloe vera, showing thermal properties and transitions. Please click here to view a larger version of this figure.

Cumulative drug release graph over time for different concentration ratios; data trend analysis.
Figure 6: Cumulative drug release from hydrogel films. Cumulative drug release from fusidic acid-loaded alginate/Aloe vera hydrogel films at different ratios: (A) 100:0, (B) 90:10, (C) 80:20, and (D) 75:25. The error bars represent standard deviation (SD), with n = 3. Please click here to view a larger version of this figure.

Film samplesThickness (mm)
A (100:0)0.11 ± 0.01
B (90:10)0.13 ± 0.01
C (80:20)0.12 ± 0.01
D (75:25)0.09 ± 0.01

Table 1: Thickness of hydrogel film formulations. Measurements of the thickness of various alginate/Aloe vera hydrogel film formulations, with n = 3.

SamplesReduction in water volume (mL)Occlusivity factor
Control2.50 ± 0.00-
A (100:0)2.50 ± 0.410
B (90:10)2.17 ± 0.2413.2 ± 0.5
C (80:20)2.00 ± 0.1120.0 ± 0.3*
D (75:25)2.00 ± 0.0220.0 ± 0.21*

Table 2: Reduction in water volume and occlusivity factor. Data on the reduction in water volume (mL) and occlusivity factor of the alginate/Aloe vera hydrogel film formulations, with n = 3. *p≤ 0.005.

Zero OrderFirst OrderKorsmeyer-PeppasHiguchi
F1 (100:0)R20.9950.66070.99250.9142
F2 (90:10)R20.9950.6670.99170.9141
F3 (80:20)R20.9950.66740.99170.9141
F4 (75:25)R20.9950.66740.99170.9141

Table 3: Release kinetics of fusidic acid. Correlation coefficients and release kinetics of fusidic acid from the hydrogel formulations, demonstrating the mathematical models used in the analysis.

Discussion

Fusidic acid was incorporated in alginate hydrogel films with various ratios of Aloe vera and glycerin. The presence of Aloe vera did not affect the appearance, but a decrease in viscosity was observed in the solutions containing Aloe vera during preparation. The findings from thickness testing suggest that the inclusion of Aloe vera may have some impact on film thickness to a certain extent, but it is not considered significant. In general, there is not a single ideal thickness that suits all applications. However, research indicated that the adhesive and mechanical properties of films are influenced by thickness, with thinner films potentially leading to faster water vapor transition rates and better maintenance of a moist environment for wound healing14.

The study on the swelling capacity of hydrogels is a key focus of research, as it aims to assess the ability of polymers to absorb different liquids. Findings show that the hydrophilic characteristics of Aloe vera significantly contribute to improving the films' swelling behavior. The increased swelling indices indicate that Aloe vera facilitated greater water absorption, possibly by retaining moisture and creating a hydrated gel-like structure within the film matrix15. The observed swelling behavior of the hydrogel films may be due to the polysaccharide content of Aloe vera. At low levels, polysaccharides may hinder the connection between alginate chains, resulting in a less compact structure and potentially less initial swelling. However, at higher concentrations, these polysaccharides can aid in cross-linking, creating a denser network capable of retaining more water and increasing the swelling index16.

An edible film's water vapor permeability (WVP) is determined by the proportion of hydrophilic and non-hydrophilic groups contained in the film. This ratio plays a major role in how the film matrix interacts with the molecules of water17. The incorporation of Aloe vera reduced the WVP of the alginate films. Similar results were obtained in another study investigating the effect of chitosan and Aloe vera extract concentrations on the physicochemical properties of chitosan biofilms, where a decrease in water vapor permeability was reported with the addition of Aloe vera18. The reduction of WVP may result from the interaction between the large-molecular-size polysaccharides found in Aloe vera and alginate, which minimizes the total intermolecular space available for water movement19. As a result, although the effect is insignificant, the hydrogel films incorporating Aloe vera demonstrated an enhanced occlusive effect compared to the control film. This can create a warmer and moist environment within the wound site, potentially aiding wound healing by reducing tissue necrosis and facilitating cell communication20.

All hydrogel film samples showed a gradual drug release, likely attributed to the compact structure of the hydrogels21. The results demonstrate that an increase in Aloe vera content leads to a minor slowing in drug release, promoting a prolonged drug release effect. This aligns with the findings of Mahmood et al., indicating that utilizing Aloe vera-based polymeric networks offers an effective method for achieving sustained drug delivery22. FTIR analysis is essential for rapidly and efficiently identifying encapsulated chemical molecules. It is particularly valuable for examining chemical alterations within polymers, such as changes in stretching or bending bands resulting from drug incorporation23. All peaks associated with fusidic acid were found to be absent in all fusidic acid-loaded hydrogels, indicating the successful incorporation of the fusidic acid into the hydrogels. According to the findings shown in Figure 4, the hydrogel film loaded with fusidic acid displayed a broad peak between 103 °C to 170 °C, with no evident components or drug melting peaks. This indicates that the drug and components were evenly distributed within the hydrogel at a molecular level, which suggests that the hydrogel system was successfully formed and that the ingredients were well incorporated into the cross-linked rigid polymer network of the hydrogel22. The release kinetic of fusidic acid was determined based on the highest regression coefficient (R2) values23. The findings of R2 values suggest that the zero-order model most accurately describes the release of fusidic acid from the polymer, indicating a consistent release rate independent of the remaining drug quantity. This is consistent with the known applications of zero-order kinetics in modified release systems, such as transdermal patches, where the drug diffuses through a polymer membrane at a constant rate. Zero-order drug delivery systems have the potential to improve patient compliance and reduce adverse side effects due to frequent dosing24,25. Cross-linked alginate/chitosan hydrogel films with 0.5 M of CaCl2 were reported to show zero-order release kinetic previously. Lowering the CaCl2 cross-linking resulted in shifting from zero order to the Korsmeyer-Peppas model26.

Limitations
While solvent casting and cross-linking with CaCl2 offer a simple approach to hydrogel film preparation, they have limitations. Factors such as CaCl2 concentration, alginate composition, and casting conditions can influence cross-linking while achieving precise control can be challenging. Excessive cross-linking with CaCl2 was reported to lead to brittle films prone to cracking or breaking. The mechanical properties (strength, elasticity) of the films might vary depending on the degree of cross-linking achieved, leading to inconsistency27,28. In conclusion, there are a number of limitations related to mechanical strength, water sensitivity, uniformity, processing conditions, adhesion, barrier properties, and environmental impact that should be carefully evaluated depending on the intended application of the films, even though solvent casting with alginate and Aloe vera offers advantages like biocompatibility and potential bioactivity. Furthermore, the solvent casting method's simplicity makes it a good choice for production on a lab scale. Therefore, in order to guarantee appropriate solvent evaporation and film formation over a greater surface area, scaling up can necessitate certain tools and adjustments.

Disclosures

The authors have nothing to disclose.

Acknowledgements

This study was supported by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R30), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia. This research was funded by the Researchers Supporting Project number (RSPD2024R811), King Saud University, Riyadh, Saudi Arabia.

Materials

List of materials used in this article
NameCompanyCatalog NumberComments
Aloe veraLocal supplier, Kuala Lumpur, MalaysiaIt was raw aloe vera bark and prepared the materials in our lab
Calcium ChlorideR&M Chemicals
Differential Scanning CalorimetryNetzsch-GruppeDSC 300 Caliris
FTIR spectroscopyPerkin Elmer107914
Fusidic AcidSigma-Aldrich, St. Louis, MO, USAPHR2810certified reference material, pharmaceutical secondary standard
Glycerin Sigma-Aldrich, St. Louis, MO, USAPHR1020United States Pharmacopeia (USP) Reference Standard
Micrometer Screw GaugeBlomker Industries, Malaysia
NETZSCH proteus software Netzsch-GruppeDSC 300 Caliris
Phosphate Buffer SalineSigma-Aldrich, St. Louis, MO, USAP4417Tablets
Sodium alginateSigma-Aldrich, St. Louis, MO, USAW201502
thermal analysis instrument NETZSCH DSC Caliris
UV-SPECTROPHOTOMETER / UV LINE-9400 SECOMAM/ 8512047

References

  1. Bandyopadhyay, D. Topical antibacterials in dermatology. Indian J Dermatol. 66 (2), 117-125 (2021).
  2. Williamson, D. A., Carter, G. P., Howden, B. P. Current and emerging topical antibacterials and antiseptics: agents, action, and resistance patterns. Clin Microbiol Rev. 30, 827-860 (2017).
  3. Bonamonte, D., Belloni Fortina, A., Neri, L., Patrizi, A. Fusidic acid in skin infections and infected atopic eczema. G Ital Dermatol Venereol. 149 (4), 453-459 (2014).
  4. Curbete, M. M., Nunes, R. A. Critical review of the properties of fusidic acid and analytical methods for its determination. Crit Rev Anal Chem. 46 (4), 352-360 (2015).
  5. Zhao, C., Zhou, L., Chiao, M., Yang, W. Antibacterial hydrogel coating: Strategies in surface chemistry. Adv Colloid Interface. 285, 102280-102280 (2020).
  6. Ahmed, E. M. Hydrogel- Preparation, characterization, and applications: A review. J Adv Res. 6, 105-121 (2015).
  7. Stan, D., et al. Wound healing applications of creams and "smart" hydrogels. Exp Dermatol. 30 (9), 1218-1232 (2021).
  8. Cole, L., Heard, C. M. Skin permeation enhancement potential of Aloe vera and a proposed mechanism of action based upon size exclusion and pull effect. Int J Pharm. 333 (1-2), 10-16 (2007).
  9. Sharma, K., Mittal, A., Chauhan, N. Aloe vera as penetration enhancer. Int J Drug Dev Res. 7, 31-43 (2015).
  10. Parhi, R., Suresh, P., Mondal, S., Kumar, P. M. Novel penetration enhancers for skin applications: A Review. Curr Drug Deliv. 9 (2), 219-230 (2012).
  11. Hadi, A., Nawab, A., Alam, F., Zehra, K. Alginate/Aloe vera films reinforced with tragacanth gum. Food Chemistry: Mol Sci. 30 (4), 100105(2022).
  12. Gull, N., et al. In vitro study of chitosan-based multi-responsive hydrogels as drug release vehicles: a preclinical study. RSC Adv. 9 (53), 31078-31091 (2019).
  13. Ciarleglio, G., Cinti, F., Toto, E., Santonicola, M. G. Synthesis and characterization of alginate gel beads with embedded zeolite structures as carriers of hydrophobic curcumin. Gels. 9 (9), 714(2023).
  14. Dong, H., et al. Smart polycationic hydrogel dressing for dynamic wound healing. Small. 18 (25), 2201620(2022).
  15. Giz, A. S., et al. A detailed investigation of the effect of calcium cross-linking and glycerol plasticizing on the physical properties of alginate films. Int J Biol Macromol. 148, 49-55 (2020).
  16. Fadhilah, S., Aisyah, N., Mohd, N., Mat, K. A. Sodium alginate film: The effect of crosslinker on physical and mechanical properties. IOP Conf Ser Mater Sci. 509, 012063(2019).
  17. Kudłacik-Kramarczyk, S., et al. Investigations on the impact of the introduction of the Aloe vera into the hydrogel matrix on cytotoxic and hydrophilic properties of these systems considered as potential wound dressings. Mater Sci Eng C. 123, 111977(2021).
  18. Pereira, R., et al. Development of novel alginate based hydrogel films for wound healing applications. Int J Biol Macromol. 52, 221-230 (2013).
  19. Hadi, A., Nawab, A., Alam, F., Zehra, K. Physical, mechanical, optical, barrier, and antioxidant properties of sodium alginate-Aloe vera biocomposite film. J Food Process. 45 (5), e15444(2021).
  20. Yoshida, C. M., et al. Effect of chitosan and Aloe vera extract concentrations on the physicochemical properties of chitosan biofilms. Polymers. 13 (8), 1187(2021).
  21. Nuutila, K., Eriksson, E. Moist wound healing with commonly available dressings. Adv Wound Care. 10 (12), 685-698 (2021).
  22. Naeem, F., et al. pH-responsive cross-linked polymeric matrices based on natural polymers: effect of process variables on swelling characterization and drug delivery properties. BioImpacts: BI. 7 (3), 177(2017).
  23. Mahmood, A., et al. Aloe vera-based polymeric network: A promising approach for sustained drug delivery, development, characterization, and in vitro evaluation. Gels. 9 (6), 474(2023).
  24. Kamaraj, N., Rajaguru, P. Y., Issac, P., Sundaresan, S. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles. Asian J Pharm Sci. 11 (4), 353-362 (2017).
  25. Chalitangkoon, J., Wongkittisin, M., Monvisade, P. Silver loaded hydroxyethylacryl chitosan/sodium alginate hydrogel films for controlled drug release wound dressings. Int J Biol Macromol. 159, 194-203 (2020).
  26. Laracuente, M. L., Yu, M. H., McHugh, K. J. Zero-order drug delivery: State of the art and future prospects. J Control Release. 327, 834-856 (2020).
  27. Wang, Y., et al. A sustained zero-order release carrier for long-acting, peakless basal insulin therapy. J Mater Chem B. 8 (9), 1952-1959 (2020).
  28. Unagolla, J. M., Jayasuriya, A. C. Drug transport mechanisms and in vitro release kinetics of vancomycin encapsulated chitosan-alginate polyelectrolyte microparticles as a controlled drug delivery system. Eur J Pharm Sci. 114, 199-209 (2018).

Reprints and Permissions

Request permission to reuse the text or figures of this JoVE article

Request Permission

Tags

Fusidic Acid HydrogelHydrogel Film PreparationSolvent CastingWound HealingTopical Drug DeliveryTransdermal Drug DeliverySwelling BehaviorWater Vapor PermeabilityFTIR Analysis

Related Articles