Abstract
In this study, alginate and carboxymethyl cellulose (CMC) were used to create films to serve as materials for wound dressing applications. These films were obtained by casting as monolayer (ML) and bilayer (BL) structures with and without diclofenac (MLD and BLD, respectively). Morphological characteristics of the films, incorporation efficiency, mechanical properties, water behavior properties, and release kinetics in aqueous media were evaluated. In addition, the mass transfer mechanisms were determined by fitting mathematical models to the experimental data. Bilayer films showed higher diclofenac incorporation efficiency (77.3%) than the monolayer films (57.5%), and both morphological structures were homogeneous and cohesive. The incorporation of diclofenac lowered the mechanical properties of the films without modifying the water absorption capacity. The BLD film had a slower release time (600 min) than the MLD (420 min), thus demonstrating the drug-free layer acts as a barrier to mass transfer and reduces the burst effect. The release from both films was influenced by diffusion; the apparent diffusion coefficients were in the order of 10–14 m2 s−1. MLD had pseudo-Fickian diffusion while BLD had anomalous diffusion. This study demonstrated that the alginate and CMC-based matrices have potential to be used as drug-delivery systems for wound dressing applications.
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References
Acuña V, Ginebreda A, Mor JR, Petrovic M, Sabater S, Sumpter J, Barceló D (2015) Balancing the health benefits and environmental risks of pharmaceuticals: diclofenac as an example. Environ Int 85:327–333. https://doi.org/10.1016/j.envint.2015.09.023
Aderibigbe BA, Buyana B (2018) Alginate in wound dressings. Pharmaceutics 10:42. https://doi.org/10.3390/pharmaceutics10020042
AL-Kahtani AA, Sherigara BS (2014) Semi-interpenetrating network of acrylamide-grafted-sodium alginate microspheres for controlled release of diclofenac sodium, preparation and characterization. Colloids Surf B Biointerfaces 115:132–138. https://doi.org/10.1016/j.colsurfb.2013.11.040
ASTM D88-02 (2002) Standard test method for tensile properties of thin plastic sheeting. In: Annual Book of ASTM, American Society for Testing and Materials. Philadelphia, pp 1–11
ASTM E96 / E96M-10 (2010) Standard test methods for water vapor transmission of materials. In: Annual Book of ASTM, American Society for Testing and Materials. Philadelphia, pp 1–10
Bechert K, Abraham SE (2009) Pain management and wound care. J Am Coll Certif Wound Spec 1:65–71. https://doi.org/10.1016/j.jcws.2008.12.001
Bierhalz ACK, Moraes ÂM (2016) Tuning the properties of alginate-chitosan membranes by varying the viscosity and the proportions of polymers. J Appl Polym Sci. https://doi.org/10.1002/app.44216
Bierhalz ACK, Da Silva MA, Kieckbusch TG (2012) Natamycin release from alginate/pectin films for food packaging applications. J Food Eng 110:18–25. https://doi.org/10.1016/j.jfoodeng.2011.12.016
Boateng JS, Matthews KH, Stevens HNE, Eccleston GM (2008) Wound healing dressings and drug delivery systems: a review. J Pharm Sci 97:2892–2923. https://doi.org/10.1002/jps.21210
Boateng JS, Pawar HV, Tetteh J (2013) Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing. Int J Pharm 441:181–191. https://doi.org/10.1016/j.ijpharm.2012.11.045
Bonilla P, Arias EM, Solans C, García-Celma MJ (2018) Influence of crosslinked alginate on drug release from highly concentrated emulsions. Colloids Surf A Physicochem Eng Asp 536:148–155. https://doi.org/10.1016/j.colsurfa.2017.07.026
Costa P, Lobo JMS (2001) Modeling and comparison of dissolution profiles. Eur J Pharm Sci 13:123–133. https://doi.org/10.1016/S0928-0987(01)00095-1
Crank J (1975) The mathematics of diffusion, 2ndd edn. Clarendon Press, Oxford
Eskandarinia A, Kefayat A, Agheb M, Rafienia M, Amini Baghbadorani M, Navid S, Ebrahimpour K, Khodabakhshi D, Ghahremani F (2020) A novel bilayer wound dressing composed of a dense polyurethane/propolis membrane and a biodegradable polycaprolactone/gelatin nanofibrous scaffold. Sci Rep 10:3063. https://doi.org/10.1038/s41598-020-59931-2
Finlay AY, Edwards PH, Harding KG (1989) “Fingertip unit” in dermatology. Lancet 334:155. https://doi.org/10.1016/S0140-6736(89)90204-3
Frescos N (2011) What causes wound pain? J Foot Ankle Res 4:P22. https://doi.org/10.1186/1757-1146-4-S1-P22
Han Y, Yu M, Wang L (2018) Physical and antimicrobial properties of sodium alginate/carboxymethyl cellulose films incorporated with cinnamon essential oil. Food Packag Shelf Life 15:35–42. https://doi.org/10.1016/j.fpsl.2017.11.001
Higuchi T (1961) Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 50:874–875. https://doi.org/10.1002/jps.2600501018
Huang RYM, Pal R, Moon GY (1999) Characteristics of sodium alginate membranes for the pervaporation dehydration of ethanol–water and isopropanol–water mixtures. J Memb Sci 160:101–113. https://doi.org/10.1016/S0376-7388(99)00071-X
Jang J, Seol Y-J, Kim HJ, Kundu J, Kim SW, Cho D-W (2014) Effects of alginate hydrogel cross-linking density on mechanical and biological behaviors for tissue engineering. J Mech Behav Biomed Mater 37:69–77. https://doi.org/10.1016/j.jmbbm.2014.05.004
Jin SG, Kim KS, Kim DW, Kim DS, Seo YG, Go TG, Youn YS, Kim JO, Yong CS, Choi HG (2016) Development of a novel sodium fusidate-loaded triple polymer hydrogel wound dressing: Mechanical properties and effects on wound repair. Int J Pharm 497:114–122. https://doi.org/10.1016/j.ijpharm.2015.12.007
Juneja P, Kaur B, Odeku OA, Singh I (2014) Development of corn starch-neusilin UFL2 conjugate as tablet superdisintegrant: formulation and evaluation of fast disintegrating tablets. J Drug Deliv 2014:1–13. https://doi.org/10.1155/2014/827035
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15:25–35. https://doi.org/10.1016/0378-5173(83)90064-9
Lamoudi L, Chaumeil JC, Daoud K (2016) Swelling, erosion and drug release characteristics of Sodium Diclofenac from heterogeneous matrix tablets. J Drug Deliv Sci Technol 31:93–100. https://doi.org/10.1016/j.jddst.2015.12.005
Lan W, He L, Liu Y (2018) Preparation and properties of sodium carboxymethyl cellulose/sodium alginate/chitosan composite film. Coatings. https://doi.org/10.3390/coatings8080291
Lazarus GS (1994) Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol 130:489–493. https://doi.org/10.1001/archderm.1994.01690040093015
Long CC, Finlay AY (1991) The finger-tip unit-a new practical measure. Clin Exp Dermatol 16:444–447. https://doi.org/10.1111/j.1365-2230.1991.tb01232.x
Ma J, Wang H, He B, Chen J (2001) A preliminary in vitro study on the fabrication and tissue engineering applications of a novel chitosan bilayer material as a scaffold of human neofetal dermal fibroblasts. Biomaterials 22:331–336. https://doi.org/10.1016/S0142-9612(00)00188-5
Manosroi A, Chankhampan C, Manosroi W, Manosroi J (2013) Transdermal absorption enhancement of papain loaded in elastic niosomes incorporated in gel for scar treatment. Eur J Pharm Sci 48:474–483. https://doi.org/10.1016/j.ejps.2012.12.010
Maver T, Hribernik S, Mohan T, Smrke DM, Maver U, Stana-Kleinschek K (2015) Functional wound dressing materials with highly tunable drug release properties. RSC Adv 5:77873–77884. https://doi.org/10.1039/C5RA11972C
Maver T, Gradišnik L, Smrke DM, Stana Kleinschek K, Maver U (2019) Systematic evaluation of a diclofenac-loaded carboxymethyl cellulose-based wound dressing and its release performance with changing pH and temperature. AAPS PharmSciTech 20:29. https://doi.org/10.1208/s12249-018-1236-4
Mi FL, Shyu SS, Wu YB, Schoung JY, Tsai YH, Bin HY, Hao JY (2002) Control of wound infections using a bilayer chitosan wound dressing with sustainable antibiotic delivery. J Biomed Mater Res 59:438–449. https://doi.org/10.1002/jbm.1260
Mogoşanu GD, Grumezescu AM (2014) Natural and synthetic polymers for wounds and burns dressing. Int J Pharm 463:127–136. https://doi.org/10.1016/j.ijpharm.2013.12.015
Momoh FU, Boateng JS, Richardson SCW, Chowdhry BZ, Mitchell JC (2015) Development and functional characterization of alginate dressing as potential protein delivery system for wound healing. Int J Biol Macromol 81:137–150. https://doi.org/10.1016/j.ijbiomac.2015.07.037
Muller J, González-Martínez C, Chiralt A (2017) Poly(lactic) acid (PLA) and starch bilayer films, containing cinnamaldehyde, obtained by compression moulding. Eur Polym J 95:56–70. https://doi.org/10.1016/j.eurpolymj.2017.07.019
Ng S-F, Tan S-L (2015) Development and in vitro assessment of alginate bilayer films containing the olive compound hydroxytyrosol as an alternative for topical chemotherapy. Int J Pharm 495:798–806. https://doi.org/10.1016/j.ijpharm.2015.09.057
Norajit K, Kim KM, Ryu GH (2010) Comparative studies on the characterization and antioxidant properties of biodegradable alginate films containing ginseng extract. J Food Eng 98:377–384. https://doi.org/10.1016/j.jfoodeng.2010.01.015
Oliveira AF, Silveira CB, Ernani PR, Balbinot ES, Soldi V (2011) Potassium Ions release from polysaccharide films. J Braz Chem Soc 22:211–216. https://doi.org/10.1590/S0103-50532011000200004
Oyane A, Kim H-M, Furuya T, Kokubo T, Miyazaki T, Nakamura T (2003) Preparation and assessment of revised simulated body fluids. J Biomed Mater Res 65A:188–195. https://doi.org/10.1002/jbm.a.10482
Pawar HV, Tetteh J, Boateng JS (2013) Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac. Colloids Surf B Biointerfaces 102:102–110. https://doi.org/10.1016/j.colsurfb.2012.08.014
Peppas NA, Sahlin JJ (1989) A simple equation for the description of solute release. III. Coupling of diffusion and relaxation. Int J Pharm 57:169–172. https://doi.org/10.1016/0378-5173(89)90306-2
Peretiatko CDS, Hupalo EA, Campos JRDR, Parabocz CRB (2018) Efficiency of zinc and calcium ion crosslinking in alginate-coated nitrogen fertilizer. Orbital 10:218–225. https://doi.org/10.17807/orbital.v10i3.1103
Pimenta AFR, Ascenso J, Fernandes JCS, Colaço R, Serro AP, Saramago B (2016) Controlled drug release from hydrogels for contact lenses: drug partitioning and diffusion. Int J Pharm 515:467–475. https://doi.org/10.1016/j.ijpharm.2016.10.047
Polo Fonseca L, Trinca RB, Felisberti MI (2018) Amphiphilic polyurethane hydrogels as smart carriers for acidic hydrophobic drugs. Int J Pharm 546:106–114. https://doi.org/10.1016/j.ijpharm.2018.05.034
Ramli NA, Wong TW (2011) Sodium carboxymethylcellulose scaffolds and their physicochemical effects on partial thickness wound healing. Int J Pharm 403:73–82. https://doi.org/10.1016/j.ijpharm.2010.10.023
Rezvanian M, Amin MCIM, Ng S-F (2016) Development and physicochemical characterization of alginate composite film loaded with simvastatin as a potential wound dressing. Carbohydr Polym 137:295–304. https://doi.org/10.1016/j.carbpol.2015.10.091
Rodrigues AP, Sanchez EMS, da Costa AC, Moraes ÂM (2008) The influence of preparation conditions on the characteristics of chitosan-alginate dressings for skin lesions. J Appl Polym Sci 109:2703–2710
Ruela ALM, Perissinato AG, de Lino ME, Mudrik PS, Pereira GR (2016) Evaluation of skin absorption of drugs from topical and transdermal formulations. Braz J Pharm Sci 52:527–544. https://doi.org/10.1590/s1984-82502016000300018
Santana AA, Kieckbusch TG (2013) Physical evaluation of biodegradable films of calcium alginate plasticized with polyols. Braz J Chem Eng 30:835–845. https://doi.org/10.1590/S0104-66322013000400015
Shivakumar H, Desai B, Deshmukh G (2008) Design and optimization of diclofenac sodium controlled release solid dispersions by response surface methodology. Indian J Pharm Sci 70:22. https://doi.org/10.4103/0250-474X.40327
Siepmann J, Podual K, Sriwongjanya M, Peppas NA, Bodmeier R (1999) A new model describing the swelling and drug release kinetics from hydroxypropyl methylcellulose tablets. J Pharm Sci 88:65–72. https://doi.org/10.1021/js9802291
Sim YC, Nam YS, Shin YH, Shin E, Kim S, Chang IS, Rhee JS (2003) Proteolytic enzyme conjugated to SC-glucan as an enzymatic transdermal drug penetration enhancer. Pharmazie 58:252–256
Souza RFB, Souza FCB, Moraes ÂM (2016) Polysaccharide-based membranes loaded with erythromycin for application as wound dressings. J Appl Polym Sci 133:1. https://doi.org/10.1002/app.43428
Sritweesinsub W, Charuchinda S (2015) Alginate/carboxymethyl cellulose hydrogel films in relation to crosslinking with glutaraldehyde and copper sulfate. MATEC Web Conf 30:2–5. https://doi.org/10.1051/matecconf/20153002005
Swamy BY, Yun Y-S (2015) In vitro release of metformin from iron (III) cross-linked alginate–carboxymethyl cellulose hydrogel beads. Int J Biol Macromol 77:114–119. https://doi.org/10.1016/j.ijbiomac.2015.03.019
Thu H-E, Ng S-F (2013) Gelatine enhances drug dispersion in alginate bilayer film via the formation of crystalline microaggregates. Int J Pharm 454:99–106. https://doi.org/10.1016/j.ijpharm.2013.06.082
Thu H-E, Zulfakar MH, Ng S-F (2012) Alginate based bilayer hydrocolloid films as potential slow-release modern wound dressing. Int J Pharm 434:375–383. https://doi.org/10.1016/j.ijpharm.2012.05.044
Tong Q, Xiao Q, Lim L-T (2008) Preparation and properties of pullulan–alginate–carboxymethylcellulose blend films. Food Res Int 41:1007–1014. https://doi.org/10.1016/j.foodres.2008.08.005
Trevisol TC, Fritz ARM, de Souza SMAGU, Bierhalz ACK, Valle JAB (2019) Alginate and carboxymethyl cellulose in monolayer and bilayer films as wound dressings: effect of the polymer ratio. J Appl Polym Sci 136:46941. https://doi.org/10.1002/app.46941
Ulubay M, Yurt KK, Kaplan AA, Atilla MK (2018) The use of diclofenac sodium in urological practice: a structural and neurochemical based review. J Chem Neuroanat 87:32–36. https://doi.org/10.1016/j.jchemneu.2017.02.005
Uz M, Altınkaya SA (2011) Development of mono and multilayer antimicrobial food packaging materials for controlled release of potassium sorbate. LWT Food Sci Technol 44:2302–2309. https://doi.org/10.1016/j.lwt.2011.05.003
Vinklárková L, Masteiková R, Vetchý D, Doležel P, Bernatonienė J (2015) Formulation of novel layered sodium carboxymethylcellulose film wound dressings with ibuprofen for alleviating wound pain. Biomed Res Int 2015:1–11. https://doi.org/10.1155/2015/892671
Willis JV, Kendall MJ, Flinn RM, Thornhill DP, Welling PG (1979) The pharmacokinetics of diclofenac sodium following intravenous and oral administration. Eur J Clin Pharmacol 16:405–410. https://doi.org/10.1007/BF00568201
Ye J, Ma D, Qin W, Liu Y (2018) Physical and antibacterial properties of sodium alginate—sodium carboxymethylcellulose films containing Lactococcus lactis. Molecules 23:2645. https://doi.org/10.3390/molecules23102645
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The authors thank the the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for financial support, the Laboratório Central de Microscopia Eletrônica and Laboratório de Central de Análises of the Department of Chemical and Food Engineering, of Federal University of Santa Catarina.
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Trevisol, T.C., Scartazzini, L., Valério, A. et al. Diclofenac release from alginate/carboxymethyl cellulose mono and bilayer films for wound dressing applications. Cellulose 27, 6629–6642 (2020). https://doi.org/10.1007/s10570-020-03217-3
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DOI: https://doi.org/10.1007/s10570-020-03217-3