Three porous matrices based on poly(lactic acid) are proposed herein for the controlled release of amikacin. The materials were fabricated by the method of spraying a surface liquid. Description is given as to the possibility of employing a modifier, such as a silica nanocarrier, for prolonging the release of amikacin, in addition to using chitosan to improve the properties of the materials, e.g., stability and sorption capacity. Depending on their actual composition, the materials exhibited varied efficacy for drug loading, as follows: 25.4 ± 2.2 μg/mg (matrices with 0.05% w/v of chitosan), 93 ± 13 μg/mg (with 0.08% w/v SiO2 amikacin modified nanoparticles), and 96 ± 34 μg/mg (matrices without functional additives). An in vitro study confirmed extended release of the drug (amikacin, over 60 days), carried out in accordance with the mathematical Kosmyer-Pepas model for all the materials tested. The matrices were also evaluated for their effectiveness in inhibiting the growth of bacteria such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent research was conducted on the transdermal absorption, morphology, elemental composition, and thermogravimetric properties of the released drug.

Centre of Polymer Systems University Institute Tomas Bata University in Zlín Tomáše Bati 5678 Street 760 01 Zlín Czech Republic

Department of Analytical Chemistry Faculty of Chemistry Gdańsk University of Technology 11 12 G Narutowicza Street 80 233 Gdańsk Poland

Department of Polymer Technology Faculty of Chemistry Gdańsk University of Technology 11 12 G Narutowicza Street 80 233 Gdańsk Poland

Zobrazit více v PubMed

Macha I.J., Muna M.M., Magere J.L. In vitro study and characterization of cotton fabric PLA composite as a slow antibiotic delivery device for biomedical applications. J. Drug Deliv. Sci. Technol. 2018;43:172–177. doi: 10.1016/j.jddst.2017.10.005. DOI

Saghazadeh S., Rinoldi C., Schot M., Kashaf S.S., Sharifi F., Jalilian E., Nuutila K., Giatsidis G., Mostafalu P., Derakhshandeh H., et al. Drug delivery systems and materials for wound healing applications. Adv. Drug Deliv. Rev. 2018;127:138–166. doi: 10.1016/j.addr.2018.04.008. PubMed DOI PMC

Zhang L., Tai Y., Liu X., Liu Y., Dong Y., Liu Y., Yang C., Kong D., Qi C., Wang S., et al. Natural polymeric and peptide-loaded composite wound dressings for scar prevention. Appl. Mater. Today. 2021;25:101186. doi: 10.1016/j.apmt.2021.101186. DOI

Alven S., Aderibigbe B.A. Hyaluronic acid-based scaffolds as potential bioactive wound dressings. Polymers. 2021;13:2102. doi: 10.3390/polym13132102. PubMed DOI PMC

Bialik-Wąs K., Pluta K., Malina D., Barczewski M., Malarz K., Mrozek-Wilczkiewicz A. Advanced SA/PVA-based hydrogel matrices with prolonged release of Aloe vera as promising wound dressings. Mater. Sci. Eng. C. 2021;120 doi: 10.1016/j.msec.2020.111667. PubMed DOI

Liu H., Wang C., Li C., Qin Y., Wang Z., Yang F., Li Z., Wang J. A functional chiosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing. R. Soc. Chem. 2018;8:7533–7549. doi: 10.1039/c7ra13510f. PubMed DOI PMC

Iqbal N., Khan A.S., Asif A., Yar M., Haycock J.W., Rehman I.U. Recent concepts in biodegradable polymers for tissue engineering paradigms: A critical review. Int. Mater. Rev. 2019;64:91–126. doi: 10.1080/09506608.2018.1460943. DOI

Tyler B., Gullotti D., Mangraviti A., Utsuki T., Brem H. Polylactic acid (PLA) controlled delivery carriers for biomedical applications. Adv. Drug Deliv. Rev. 2016;107:163–175. doi: 10.1016/j.addr.2016.06.018. PubMed DOI

Santoro M., Shah S.R., Walker J.L., Mikos A.G. Poly(lactic acid) nanofibrous scaffolds for tissue engineering. Adv. Drug Deliv. Rev. 2016;107:206–212. doi: 10.1016/j.addr.2016.04.019. PubMed DOI PMC

Abdal-Hay A., Hussein K.H., Casettari L., Khalil K.A., Hamdy A.S. Fabrication of novel high performance ductile poly(lactic acid) nanofiber scaffold coated with poly(vinyl alcohol) for tissue engineering applications. Mater. Sci. Eng. C. 2016;60:143–150. doi: 10.1016/j.msec.2015.11.024. PubMed DOI

Wang L., Wang D., Zhou Y., Zhang Y., Li Q., Shen C. Fabrication of open-porous PCL/PLA tissue engineering scaffolds and the relationship of foaming process, morphology, and mechanical behavior. Polym. Adv. Technol. 2019;30:2539–2548. doi: 10.1002/pat.4701. DOI

Abu Ghalia M., Dahman Y. Fabrication and enhanced mechanical properties of porous PLA/PEG copolymer reinforced with bacterial cellulose nanofibers for soft tissue engineering applications. Polym. Test. 2017;61:114–131. doi: 10.1016/j.polymertesting.2017.05.016. DOI

Bi H., Feng T., Li B., Han Y. In vitro and in vivo comparison study of electrospun PLA and PLA/PVA/SA fiber membranes for wound healing. Polymers. 2020;12:839. doi: 10.3390/polym12040839. PubMed DOI PMC

Moghaddam M.A., Di Martino A., Šopík T., Fei H., Císař J., Pummerová M., Sedlařík V. Polylactide/polyvinylalcohol-based porous bioscaffold loaded with gentamicin for wound dressing applications. Polymers. 2021;13:921. doi: 10.3390/polym13060921. PubMed DOI PMC

Glinka M., Filatova K., Kucińska-Lipka J., Bergerova E.D., Wasik A., Sedlařík V. Encapsulation of Amikacin into Microparticles Based on Low-Molecular-Weight Poly(lactic acid) and Poly(lactic acid- co-polyethylene glycol) Mol. Pharm. 2021;18:2986–2996. doi: 10.1021/acs.molpharmaceut.1c00193. PubMed DOI PMC

Chen G., Ushida T., Tateishi T. Development of biodegradable porous scaffolds for tissue engineering. Mater. Sci. Eng. C. 2001;17:63–69. doi: 10.1016/S0928-4931(01)00338-1. DOI

Koosehgol S., Ebrahimian-Hosseinabadi M., Alizadeh M., Zamanian A. Preparation and characterization of in situ chitosan/polyethylene glycol fumarate/thymol hydrogel as an effective wound dressing. Mater. Sci. Eng. C. 2017;79:66–75. doi: 10.1016/j.msec.2017.05.001. PubMed DOI

Bayrakci M., Keskinates M., Yilmaz B. Antibacterial, thermal decomposition and in vitro time release studies of chloramphenicol from novel PLA and PVA nanofiber mats. Mater. Sci. Eng. C. 2021;122:111895. doi: 10.1016/j.msec.2021.111895. PubMed DOI

Hajikhani M., Emam-Djomeh Z., Askari G. Fabrication and characterization of mucoadhesive bioplastic patch via coaxial polylactic acid (PLA) based electrospun nanofibers with antimicrobial and wound healing application. Int. J. Biol. Macromol. 2021;172:143–153. doi: 10.1016/j.ijbiomac.2021.01.051. PubMed DOI

Ramirez M.S., Tolmasky M.E. Amikacin: Uses, resistance, and prospects for inhibition. Molecules. 2017;22:2267. doi: 10.3390/molecules22122267. PubMed DOI PMC

European Medicines Agency . Reflection Paper on Use of Aminoglycosides in Animals in the European Union: Development of Resistance and Impact on Human and Animal Health. Volume 44. European Medicines Agency; Amsterdam, The Netherlands: 2017. pp. 1–42.

Krause K.M., Serio A.W., Kane T.R., Connolly L.E. Aminoglycosides: An Overview. Cold Spring Harb. Perspect. Med. 2016;6:a027029. doi: 10.1101/cshperspect.a027029. PubMed DOI PMC

Duszynska W., Taccone F.S., Hurkacz M., Kowalska-Krochmal B., Wiela-Hojeńska A., Kübler A. Therapeutic drug monitoring of amikacin in septic patients. Crit. Care. 2013;17:cc12844. doi: 10.1186/cc12844. PubMed DOI PMC

Ristuccia A.M., Cunha B.A. An overview of amikacin. Ther. Drug Monit. 1985;7:12–25. doi: 10.1097/00007691-198503000-00003. PubMed DOI

Price J.S., Tencer A.F., Arm D.M., Bohach G.A. Controlled release of antibiotics from coated orthopedic implants. J. Biomed. Mater. Res. 1996;30:281–286. doi: 10.1002/(SICI)1097-4636(199603)30:3<281::AID-JBM2>3.0.CO;2-M. PubMed DOI

Brooks B.D., Sinclair K.D., Davidoff S.N., Lawson S., Williams A.G., Coats B., Grainger D.W., Brooks A.E. Molded polymer-coated composite bone void filler improves tobramycin controlled release kinetics. J. Biomed. Mater. Res. Part B Appl. Biomater. 2014;102:1074–1083. doi: 10.1002/jbm.b.33089. PubMed DOI

López-Calderón H.D., Avilés-Arnaut H., Galán Wong L.J., Almaguer-Cantú V., Laguna-Camacho J.R., Calderón-Ramón C., Escalante-Martínez J.E., Arévalo-Niño K. Cellulose Acetate Bi-Layer Scaffold Loaded with Gentamicin as Possible Wound Dressing. Polymers. 2020;12:2311. doi: 10.3390/polym12102311. PubMed DOI PMC

Merlusca I.P., Matiut D.S., Lisa G., Silion M., Gradinaru L., Oprea S., Popa I.M. Preparation and characterization of chitosan–poly(vinyl alcohol)–neomycin sulfate films. Polym. Bull. 2018;75:3971–3986. doi: 10.1007/s00289-017-2246-1. DOI

Nitanan T., Akkaramongkolporn P., Rojanarata T., Ngawhirunpat T., Opanasopit P. Neomycin-loaded poly(styrene sulfonic acid-co-maleic acid) (PSSA-MA)/polyvinyl alcohol (PVA) ion exchange nanofibers for wound dressing materials. Int. J. Pharm. 2013;448:71–78. doi: 10.1016/j.ijpharm.2013.03.011. PubMed DOI

Bakhsheshi-Rad H.R., Hadisi Z., Ismail A.F., Aziz M., Akbari M., Berto F., Chen X.B. In vitro and in vivo evaluation of chitosan-alginate/gentamicin wound dressing nanofibrous with high antibacterial performance. Polym. Test. 2020;82:106298. doi: 10.1016/j.polymertesting.2019.106298. DOI

Noel S.P., Courtney H.S., Bumgardner J.D., Haggard W.O. Chitosan sponges to locally deliver amikacin and vancomycin: A pilot in vitro evaluation. Clin. Orthop. Relat. Res. 2010;468:2074–2080. doi: 10.1007/s11999-010-1324-6. PubMed DOI PMC

Abbasi A.R., Sohail M., Minhas M.U., Khaliq T., Kousar M., Khan S., Hussain Z., Munir A. Bioinspired sodium alginate based thermosensitive hydrogel membranes for accelerated wound healing. Int. J. Biol. Macromol. 2020;155:751–765. doi: 10.1016/j.ijbiomac.2020.03.248. PubMed DOI

Singh B., Singh J. Rajneesh Application of tragacanth gum and alginate in hydrogel wound dressing’s formation using gamma radiation. Carbohydr. Polym. Technol. Appl. 2021;2:100058. doi: 10.1016/j.carpta.2021.100058. DOI

Prabu P., Dharmaraj N., Aryal S., Lee B.M., Ramesh V., Kim H.Y. Preparation and drug release activity of scaffolds containing collagen and poly(caprolactone) J. Biomed. Mater. Res. Part A. 2006;79:963–973. doi: 10.1002/jbm.a.30715. PubMed DOI

Natarajan S.K., Selvaraj S. Mesoporous silica nanoparticles: Importance of surface modifications and its role in drug delivery. RSC Adv. 2014;4:14328–14334. doi: 10.1039/c4ra00781f. DOI

Nastase S., Bajenaru L., Matei C., Mitran R.A., Berger D. Ordered mesoporous silica and aluminosilicate-type matrix for amikacin delivery systems. Microporous Mesoporous Mater. 2013;182:32–39. doi: 10.1016/j.micromeso.2013.08.018. DOI

Matica M.A., Aachmann F.L., Tøndervik A., Sletta H., Ostafe V. Chitosan as a wound dressing starting material: Antimicrobial properties and mode of action. Int. J. Mol. Sci. 2019;20:5889. doi: 10.3390/ijms20235889. PubMed DOI PMC

Kmetty Á., Litauszki K. Development of poly (lactide acid) foams with thermally expandable microspheres. Polymers. 2020;12:463. doi: 10.3390/polym12020463. PubMed DOI PMC

Gieldowska M., Puchalski M., Szparaga G., Krucińska I. Investigation of the influence of PLA molecular and supramolecular structure on the kinetics of thermal-supported hydrolytic degradation of wet spinning fibres. Materials. 2020;13:2111. doi: 10.3390/ma13092111. PubMed DOI PMC

Bakshi P.S., Selvakumar D., Kadirvelu K., Kumar N.S. Chitosan as an environment friendly biomaterial—A review on recent modifications and applications. Int. J. Biol. Macromol. 2020;150:1072–1083. doi: 10.1016/j.ijbiomac.2019.10.113. PubMed DOI

Menazea A.A., Ismail A.M., Awwad N.S., Ibrahium H.A. Physical characterization and antibacterial activity of PVA/Chitosan matrix doped by selenium nanoparticles prepared via one-pot laser ablation route. J. Mater. Res. Technol. 2020;9:9598–9606. doi: 10.1016/j.jmrt.2020.06.077. DOI

Sogias I.A., Khutoryanskiy V.V., Williams A.C. Exploring the factors affecting the solubility of chitosan in water. Macromol. Chem. Phys. 2010;211:426–433. doi: 10.1002/macp.200900385. DOI

Bonilla J., Fortunati E., Vargas M., Chiralt A., Kenny J.M. Effects of chitosan on the physicochemical and antimicrobial properties of PLA films. J. Food Eng. 2013;119:236–243. doi: 10.1016/j.jfoodeng.2013.05.026. DOI

Chen C., Liu L., Huang T., Wang Q., Fang Y. Bubble template fabrication of chitosan/poly(vinyl alcohol) sponges for wound dressing applications. Int. J. Biol. Macromol. 2013;62:188–193. doi: 10.1016/j.ijbiomac.2013.08.042. PubMed DOI

Li F.J., Zhang S.D., Liang J.Z., Wang J.Z. Effect of polyethylene glycol on the crystallization and impact properties of polylactide-based blends. Polym. Adv. Technol. 2015;26:465–475. doi: 10.1002/pat.3475. DOI

Mitran R.-A., Deaconu M., Matei C., Berger D. Mesoporous Silica as Carrier for Drug-Delivery Systems. Elsevier Inc.; Amsterdam, The Netherlands: 2019.

Berger D., Bajenaru L., Nastase S., Mitran R.A., Munteanu C., Matei C. Influence of structural, textural and surface properties of mesostructured silica and aluminosilicate carriers on aminoglycoside uptake and in vitro delivery. Microporous Mesoporous Mater. 2015;206:150–160. doi: 10.1016/j.micromeso.2014.12.022. DOI

Ovalles J.F., Gallignani M., Brunetto M.R., Rondón R.A., Ayala C. Reagent-free determination of amikacin content in amikacin sulfate injections by FTIR derivative spectroscopy in a continuous flow system. J. Pharm. Anal. 2014;4:125–131. doi: 10.1016/j.jpha.2013.08.001. PubMed DOI PMC

Ferro L., Gojkovic Z., Funk C. Statistical Methods for Rapid Quantification of Proteins, Lipids, and Carbohydrates in Nordic. Molecules. 2019;24:3237. doi: 10.3390/molecules24183237. PubMed DOI PMC

Grumezescu V., Socol G., Grumezescu A.M., Holban A.M., Ficai A., Truşcǎ R., Bleotu C., Balaure P.C., Cristescu R., Chifiriuc M.C. Functionalized antibiofilm thin coatings based on PLA-PVA microspheres loaded with usnic acid natural compounds fabricated by MAPLE. Appl. Surf. Sci. 2014;302:262–267. doi: 10.1016/j.apsusc.2013.09.081. DOI

Chieng B.W., Ibrahim N.A., Yunus W.M.Z.W., Hussein M.Z. Poly(lactic acid)/poly(ethylene glycol) polymer nanocomposites: Effects of graphene nanoplatelets. Polymers. 2014;6:93–104. doi: 10.3390/polym6010093. DOI

Lai S.M., Hsieh Y.T. Preparation and Properties of Polylactic Acid (PLA)/Silica Nanocomposites. J. Macromol. Sci. Part B Phys. 2016;55:211–228. doi: 10.1080/00222348.2016.1138179. DOI

Tang F., Li L., Chen D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012;24:1504–1534. doi: 10.1002/adma.201104763. PubMed DOI

Hashemikia S., Hemmatinejad N., Ahmadi E., Montazer M. A novel cotton fabric with anti-bacterial and drug delivery properties using SBA-15-NH2/polysiloxane hybrid containing tetracycline. Mater. Sci. Eng. C. 2016;59:429–437. doi: 10.1016/j.msec.2015.09.092. PubMed DOI

Pawar V., Bulbake U., Khan W., Srivastava R. Chitosan sponges as a sustained release carrier system for the prophylaxis of orthopedic implant-associated infections. Int. J. Biol. Macromol. 2019;134:100–112. doi: 10.1016/j.ijbiomac.2019.04.190. PubMed DOI

Gomaa S.F., Madkour T.M., Moghannem S., El-Sherbiny I.M. New polylactic acid/cellulose acetate-based antimicrobial interactive single dose nanofibrous wound dressing mats. Int. J. Biol. Macromol. 2017;105:1148–1160. doi: 10.1016/j.ijbiomac.2017.07.145. PubMed DOI

Cui S., Sun X., Li K., Gou D., Zhou Y., Hu J., Liu Y. Polylactide nanofibers delivering doxycycline for chronic wound treatment. Mater. Sci. Eng. C. 2019;104 doi: 10.1016/j.msec.2019.109745. PubMed DOI

Seo K.H., Lee K.E., Yanilmaz M., Kim J. Exploring the Diverse Morphology of Porous Poly(Lactic Acid) Fibers for Developing Long-Term Controlled Antibiotic Delivery Systems. Pharmaceutics. 2022;14:1272. doi: 10.3390/pharmaceutics14061272. PubMed DOI PMC

Chang H.I., Perrie Y., Coombes A.G.A. Delivery of the antibiotic gentamicin sulphate from precipitation cast matrices of polycaprolactone. J. Control. Release. 2006;110:414–421. doi: 10.1016/j.jconrel.2005.10.028. PubMed DOI

Posadowska U., Brzychczy-Włoch M., Pamuła E. Gentamicin loaded PLGA nanoparticles as local drug delivery system for the osteomyelitis treatment. Acta Bioeng. Biomech. 2015;17:41–47. doi: 10.5277/ABB-00188-2014-02. PubMed DOI

Sabaeifard P., Abdi-Ali A., Soudi M.R., Gamazo C., Irache J.M. Amikacin loaded PLGA nanoparticles against Pseudomonas aeruginosa. Eur. J. Pharm. Sci. 2016;93:392–398. doi: 10.1016/j.ejps.2016.08.049. PubMed DOI

Vimala K., Mohan Y.M., Sivudu K.S., Varaprasad K., Ravindra S., Reddy N.N., Padma Y., Sreedhar B., MohanaRaju K. Fabrication of porous chitosan films impregnated with silver nanoparticles: A facile approach for superior antibacterial application. Colloids Surf. B Biointerfaces. 2010;76:248–258. doi: 10.1016/j.colsurfb.2009.10.044. PubMed DOI

Pillai C.K.S., Paul W., Sharma C.P. Chitin and chitosan polymers: Chemistry, solubility and fiber formation. Prog. Polym. Sci. 2009;34:641–678. doi: 10.1016/j.progpolymsci.2009.04.001. DOI

Lewandowska K. Effect of an ionic liquid on the physicochemical properties of chitosan/poly(vinyl alcohol) mixtures. Int. J. Biol. Macromol. 2020;147:1156–1163. doi: 10.1016/j.ijbiomac.2019.10.084. PubMed DOI

Lewandowska K. Miscibility and thermal stability of poly(vinyl alcohol)/chitosan mixtures. Thermochim. Acta. 2009;493:42–48. doi: 10.1016/j.tca.2009.04.003. DOI

Wang N., Yu J., Ma X. Preparation and characterization of thermoplastic starch/PLA blends by one-step reactive extrusion. Polym. Int. 2007;56:1140–1447. doi: 10.1002/pi.2302. DOI

Acosta-Ferreira S., Castillo O.S., Madera-Santana J.T., Mendoza-García D.A., Núñez-Colín C.A., Grijalva-Verdugo C., Villa-Lerma A.G., Morales-Vargas A.T., Rodríguez-Núñez J.R. Production and physicochemical characterization of chitosan for the harvesting of wild microalgae consortia. Biotechnol. Rep. 2020;28:554. doi: 10.1016/j.btre.2020.e00554. PubMed DOI PMC

Nicoli S., Santi P. Transdermal delivery of aminoglycosides: Amikacin transport and iontophoretic non-invasive monitoring. J. Control. Release. 2006;111:89–94. doi: 10.1016/j.jconrel.2005.11.008. PubMed DOI

Pandey H., Parashar V., Parashar R., Prakash R., Ramteke P.W., Pandey A.C. Controlled drug release characteristics and enhanced antibacterial effect of graphene nanosheets containing gentamicin sulfate. Nanoscale. 2011;3:4104–4108. doi: 10.1039/c1nr10661a. PubMed DOI