Abstract
One of the main reasons infected wounds go untreated is that antibiotic-resistant bacteria mainly cause infection. Vancomycin is an antibiotic used against Gram-positive bacteria, such as MRSA, but it has limited intravenous use due to its toxicity. This study describes using a local drug delivery approach at the wound site. The aim is to prepare a silk dressing containing dialdehyde starch nanoparticles loaded with vancomycin that can cure infection through the controlled release of antibiotics. First, the starch was oxidized by sodium periodate solution and converted to dialdehyde starch. Dialdehyde starch was converted into nanoparticles by the microemulsion method. Simultaneously, with nanoparticle formation, the antibiotic vancomycin (VAN), added to the solution, was loaded into the dialdehyde starch nanoparticles (DASNP). The wound dressing (SF/DASNP/VAN) was prepared by adding nanoparticles containing antibiotics to the silk fibroin (SF) solution, and then, the solution containing the nanoparticles was freeze-dried, and the nanoparticles were placed inside the silk matrix. Drug release of dressings was performed by immersion in phosphate-buffered saline, and cytotoxicity by MTT assay and antibacterial properties of dressings were investigated by the inhibition zone method. The morphology of the SF/DASNP/VAN dressing, its biocompatibility, antibacterial efficiency, and antibiotic release kinetics were assessed. The synthesized dressing has the desired biocompatibility with 69% cell viability and shows antibacterial properties against MRSA with a growth inhibition zone diameter of 12 mm. Also, VAN was successfully incorporated into the dressing, resulting in a 144-h continuous release profile. It may be concluded that the fabricated dressing based on silk and dialdehyde starch nanoparticles opens up a new option for topical administration of antibiotics. We believe its properties can be considered a new dressing for infectious wounds by reducing infection associated with controlled drug delivery.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Zaidi Z, Lanigan SW. Dermatology in Clinical Practice: Springer London; 2010.
Peiman Brouki Milan, Naser Amini, Moein Amoupour, Ali Amadikuchaksaraei, Alireza Rezapour, Farshid Sefat, et al. Scaffolds for regeneration of dermo-epidermal skin tissue. Handbook of Tissue Engineering Scaffolds: Volume Two: Elsevier Science; 2019. p. 193–209.
Boateng J, Catanzano O. Advanced therapeutic dressings for effective wound healing—a review. J Pharm Sci. 2015;104:3653–80.
Forson OA, Ayanka E, Olu-Taiwo M, Pappoe-Ashong PJ, Ayeh-Kumi PJ. Bacterial infections in burn wound patients at a tertiary teaching hospital in Accra. Ghana Ann Burns Fire Disasters. 2017;30:116–20.
Rashid A, Saqib M, Deeba F, Khan JA. Microbial profile of burn wound infections and their antibiotic sensitivity patterns at burn unit of allied hospital Faisalabad. Pak J Pharm Sci. 2019;32:247–54.
Pujji OJS, Nakarmi KK, Shrestha B, Rai SM, Jeffery SLA. The Bacteriological Profile of Burn Wound Infections at a Tertiary Burns Center in Nepal. J Burn Care Res. 2019;40:838–45.
Rezapour-Lactoee A, Yeganeh H, Gharibi R, Milan PB. Enhanced healing of a full-thickness wound by a thermoresponsive dressing utilized for simultaneous transfer and protection of adipose-derived mesenchymal stem cells sheet. J Mater Sci Mater Med. 2020;31:101.
Pulat M, Kahraman AS, Tan N, Gumusderelioglu M. Sequential antibiotic and growth factor releasing chitosan-PAAm semi-IPN hydrogel as a novel wound dressing. J Biomater Sci Polym Ed. 2013;24:807–19.
Boateng JS, Matthews KH, Stevens HN, Eccleston GM. Wound healing dressings and drug delivery systems: a review. J Pharm Sci. 2008;97:2892–923.
el Kenawy R, Worley SD, Broughton R. The chemistry and applications of antimicrobial polymers: a state-of-the-art review. Biomacromol. 2007;8:1359–84.
Dizman B, Elasri MO, Mathias LJ. Novel antibacterial polymers. ACS Symp Ser2009. p. 27–51.
Yari A, Yeganeh H, Bakhshi H. Synthesis and evaluation of novel absorptive and antibacterial polyurethane membranes as wound dressing. J Mater Sci Mater Med. 2012;23:2187–202.
Albaugh KW, Biely SA, Cavorsi JP. The effect of a cellulose dressing and topical vancomycin on methicillin-resistant Staphylococcus aureus (MRSA) and Gram-positive organisms in chronic wounds: a case series. Ostomy Wound Manage. 2013;59:34–43.
Lopez-Iglesias C, Barros J, Ardao I, Monteiro FJ, Alvarez-Lorenzo C, Gomez-Amoza JL, et al. Vancomycin-loaded chitosan aerogel particles for chronic wound applications. Carbohydr Polym. 2019;204:223–31.
Shariati A, Dadashi M, Moghadam MT, van Belkum A, Yaslianifard S, Darban-Sarokhalil D. Global prevalence and distribution of vancomycin resistant, vancomycin intermediate and heterogeneously vancomycin intermediate Staphylococcus aureus clinical isolates: a systematic review and meta-analysis. Sci Rep. 2020;10:12689.
Ziesmer J, Tajpara P, Hempel N-J, Ehrström M, Melican K, Eidsmo L, et al. Vancomycin-Loaded Microneedle Arrays against Methicillin-Resistant Staphylococcus Aureus Skin Infections. Adv Mater Technol 2021;6:2001307-.
Manfredi R, Calza L. The recent evolution of therapeutic weapons against resistant Gram-positive microorganisms. Archivos Venezolanos de Farmacología y Terapéutica. 2008;27:92–104.
Rao S, Kupfer Y, Pagala M, Chapnick E, Tessler S. Systemic absorption of oral vancomycin in patients with Clostridium difficile infection. Scand J Infect Dis. 2011;43:386–8.
Ruszczak Z, Friess W. Collagen as a carrier for on-site delivery of antibacterial drugs. Adv Drug Deliv Rev. 2003;55:1679–98.
Zhang L, Pornpattananangku D, Hu CM, Huang CM. Development of nanoparticles for antimicrobial drug delivery. Curr Med Chem. 2010;17:585–94.
Milan PB, Amini N, Mehrabi A, Mousazadeh S, Ababzadeh S, Rezapour A. Cell Sources in Cardiac Tissue Engineering: Current Choices. Curr Stem Cell Res Ther. 2021;16:745–52.
Rodrigues A, Emeje M. Recent applications of starch derivatives in nanodrug delivery. Carbohyd Polym. 2012;87:987–94.
Song D, Thio YS, Deng Y. Starch nanoparticle formation via reactive extrusion and related mechanism study. Carbohyd Polym. 2011;85:208–14.
Huang Y, Liu M, Gao C, Yang J, Zhang X, Zhang X, et al. Ultra-small and innocuous cationic starch nanospheres: preparation, characterization and drug delivery study. Int J Biol Macromol. 2013;58:231–9.
Xiao S, Liu X, Tong C, Zhao L, Liu X, Zhou A, et al. Dialdehyde starch nanoparticles as antitumor drug delivery system: An in vitro, in vivo, and immunohistological evaluation. Chin Sci Bull. 2012;57:3226–32.
Johnson JL, Yalkowsky SH. Reformulation of a new vancomycin analog: an example of the importance of buffer species and strength. AAPS PharmSciTech. 2006;7:E5.
Chen Y, Hao Y, Ting K, Li Q, Gao Q. Preparation and emulsification properties of dialdehyde starch nanoparticles. Food Chem. 2019;286:467–74.
Liu J, Lu F, Chen H, Bao R, Li Z, Lu B, et al. Healing of skin wounds using a new cocoon scaffold loaded with platelet-rich or platelet-poor plasma. RSC Adv. 2017;7:6474–85.
Wharram SE, Zhang X, Kaplan DL, McCarthy SP. Electrospun silk material systems for wound healing. Macromol Biosci. 2010;10:246–57.
Shpichka A, Butnaru D, Bezrukov EA, Sukhanov RB, Atala A, Burdukovskii V, et al. Skin tissue regeneration for burn injury. Stem Cell Res Ther. 2019;10:94.
Lago K, Decker CF, Chung KK, Blyth D. Difficult to Treat Infections in the Burn Patient. Surg Infect (Larchmt). 2021;22:95–102.
Lee WY, Um IC, Kim MK, Kwon KJ, Kim SG, Park YW. Effectiveness of Woven Silk Dressing Materials on Full-skin Thickness Burn Wounds in Rat Model. Maxillofac Plast Reconstr Surg. 2014;36:280–4.
Farokhi M, Mottaghitalab F, Fatahi Y, Khademhosseini A, Kaplan DL. Overview of Silk Fibroin Use in Wound Dressings. Trends Biotechnol. 2018;36:907–22.
Johari N, Moroni L, Samadikuchaksaraei A. Tuning the conformation and mechanical properties of silk fibroin hydrogels. European Polymer Journal 2020;134:109842.
Wongsagon R, Shobsngob S, Varavinit S. Preparation and physicochemical properties of dialdehyde tapioca starch. Starch-Stärke. 2005;57:166–72.
Chin SF, Azman A, Pang SC. Size controlled synthesis of starch nanoparticles by a microemulsion method. Journal of Nanomaterials 2014;2014.
Pritchard EM, Valentin T, Panilaitis B, Omenetto F, Kaplan DL. Antibiotic-Releasing Silk Biomaterials for Infection Prevention and Treatment. Adv Func Mater. 2013;23:854–61.
Gharibi R, Shaker A, Rezapour-Lactoee A, Agarwal S. Antibacterial and Biocompatible Hydrogel Dressing Based on Gelatin- and Castor-Oil-Derived Biocidal Agent. ACS Biomater Sci Eng. 2021;7:3633–47.
Lan Y, Li W, Jiao Y, Guo R, Zhang Y, Xue W, et al. Therapeutic efficacy of antibiotic-loaded gelatin microsphere/silk fibroin scaffolds in infected full-thickness burns. Acta Biomater. 2014;10:3167–76.
Nematollahi Z, Tafazzoli-Shadpour M, Zamanian A, Seyedsalehi A, Mohammad-Behgam S, Ghorbani F, et al. Fabrication of Chitosan Silk-based Tracheal Scaffold Using Freeze-Casting Method. Iran Biomed J. 2017;21:228–39.
Hivechi A, Milan PB, Modabberi K, Amoupour M, Ebrahimzadeh K, Gholipour AR, et al. Synthesis and Characterization of Exopolysaccharide Encapsulated PCL/Gelatin Skin Substitute for Full-Thickness Wound Regeneration. Polymers (Basel). 2021;13:854.
Yoo JW, Mitragotri S. Polymer particles that switch shape in response to a stimulus. Proc Natl Acad Sci U S A. 2010;107:11205–10.
SALİU O, Olatunji GA, Ajetomobi OO, Olosho AI, ABİODUN İ, Amusan G. Crystalline starch citrate biopolymer nanorods as potential stabilizers in nano and micro emulsions. Journal of the Turkish Chemical Society Section B: Chemical Engineering 2017;1:191–200.
Abbas S, Bashari M, Akhtar W, Li WW, Zhang X. Process optimization of ultrasound-assisted curcumin nanoemulsions stabilized by OSA-modified starch. Ultrason Sonochem. 2014;21:1265–74.
Cong VT, Gaus K, Tilley RD, Gooding JJ. Rod-shaped mesoporous silica nanoparticles for nanomedicine: recent progress and perspectives. Expert Opin Drug Deliv. 2018;15:881–92.
Ahmed A, Getti G, Boateng J. Ciprofloxacin-loaded calcium alginate wafers prepared by freeze-drying technique for potential healing of chronic diabetic foot ulcers. Drug Deliv Transl Res. 2018;8:1751–68.
Usman AH, Salisu AA, Danjani AG. Preparation and characterization of dialdehyde starch urea (DASU) and it’s sorption potential for Co(ii), Pb(ii) and Zn(ii) ions from aqueous solution. Bayero Journal of Pure and Applied Sciences. 2017;9:213.
Elkhodairy KA, Afifi SA, Zakaria AS. A promising approach to provide appropriate colon target drug delivery systems of vancomycin HCL: pharmaceutical and microbiological studies. Biomed Res Int 2014;2014:182197.
Zhang M, Li Z, Liu L, Sun Z, Ma W, Zhang Z, et al. preparation and characterization of vancomycin-loaded electrospun Rana chensinensis skin collagen/poly (L-lactide) nanofibers for drug delivery. Journal of Nanomaterials 2016;2016.
Gaspar LMdAC, Dórea ACS, Droppa-Almeida D, de Mélo Silva IS, Montoro FE, Alves LL, et al. Development and characterization of PLGA nanoparticles containing antibiotics. Journal of Nanoparticle Research 2018;20:1–9.
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This work was supported by the Qom University of Medical Sciences (MUQ) through research Grant No. IR.MUQ.REC.1397.82.
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S.E wrote the main manuscript. M.S carried out data analysis, validated experiments, and wrote the part of the manuscript. A.R supervised the project, prepared figures, and wrote the part of the manuscript with the insights of all other authors. All authors read and approved the final manuscript.
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Einipour, S.K., Sadrjahani, M. & Rezapour, A. Preparation and evaluation of antibacterial wound dressing based on vancomycin-loaded silk/dialdehyde starch nanoparticles. Drug Deliv. and Transl. Res. 12, 2778–2792 (2022). https://doi.org/10.1007/s13346-022-01139-0
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DOI: https://doi.org/10.1007/s13346-022-01139-0