Abstract
Projecting optimal composition for hydrogel blends, while designing sustained release formulation of hydrophilic drug, is of paramount importance. In present study, composite hydrogel incorporating ciprofloxacin (0.2% w/w) was prepared by sequential addition of polyvinyl alcohol (PVA) (20–95% w/w), starch (0–75% w/w), citric acid (5–80% w/w) as cross-linker in a heat-induced gelatinization process. A constrained simplex mixture design was adopted to rationalize the proportion of ingredients in hydrogel composition while modelling the time required for 50% drug release from the hydrogel under in-vitro conditions. Prepared hydrogels were also characterized for swelling ratio, tensile strength, and antimicrobial disc-diffusion assay. Decreasing proportion of starch relative to PVA results in a transparent hydrogel, with a high degree of equilibrium swelling (up to 104%). Drug release from all hydrogel blend arguably followed Korsmeyer-Peppas release kinetics with quasi-Fickian to non-Fickian release behaviour. The time required for 50% drug release and the hydrogel dissolution was proportional, indicating disintegration-controlled release rate. Reduced cubic-model based on the forward selection offered good agreement with experimental data (R2, 0.98 and adjusted R2 of 0.91). Optimal blend projection by the model with a mass ratio of 0.38:0.21:0.41 for PVA: Starch: citric acid was verified to be reasonably correct.
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References
Boateng J, Catanzano O (2015) Advanced Therapeutic Dressings for Effective Wound Healing—A Review. J Pharm Sci 104:3653–3680. https://doi.org/10.1002/jps.24610
Serra R, Grande R, Butrico L et al (2015) Chronic wound infections: the role of Pseudomonas aeruginosa and Staphylococcus aureus. Expert Rev Anti Infect Ther 13:605–613. https://doi.org/10.1586/14787210.2015.1023291
Roy DC, Tomblyn S, Burmeister DM et al (2015) Ciprofloxacin-Loaded Keratin Hydrogels Prevent Pseudomonas aeruginosa Infection and Support Healing in a Porcine Full-Thickness Excisional Wound. Adv Wound Care 4:457–468. https://doi.org/10.1089/wound.2014.0576
Liu X, Nielsen LH, Kłodzińska SN et al (2018) Ciprofloxacin-loaded sodium alginate/poly (lactic-co-glycolic acid) electrospun fibrous mats for wound healing. Eur J Pharm Biopharm 123:42–49. https://doi.org/10.1016/j.ejpb.2017.11.004
Unnithan AR, Barakat NAM, Tirupathi Pichiah PB et al (2012) Wound-dressing materials with antibacterial activity from electrospun polyurethane–dextran nanofiber mats containing ciprofloxacin HCl. Carbohydr Polym 90:1786–1793. https://doi.org/10.1016/j.carbpol.2012.07.071
Vermeulen H, Ubbink DT, de Zwart F et al (2007) Preferences of patients, doctors, and nurses regarding wound dressing characteristics: A conjoint analysis. Wound Repair Regen 15:302–307. https://doi.org/10.1111/j.1524-475X.2007.00230.x
Fu Y, Kao WJ (2010) Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opin Drug Deliv 7:429–444. https://doi.org/10.1517/17425241003602259
Peppas NA (2000) Hydrogels in pharmaceutical formulations. Eur J Pharm Biopharm 50:27–46. https://doi.org/10.1016/S0939-6411(00)00090-4
Jiang S, Liu S, Feng W (2011) PVA hydrogel properties for biomedical application. J Mech Behav Biomed Mater 4:1228–1233. https://doi.org/10.1016/j.jmbbm.2011.04.005
Shitole AA, Raut PW, Khandwekar A et al (2019) Design and engineering of polyvinyl alcohol based biomimetic hydrogels for wound healing and repair. J Polym Res 26:201. https://doi.org/10.1007/s10965-019-1874-6
Hoffman AS (2012) Hydrogels for biomedical applications. Adv Drug Deliv Rev 64:18–23. https://doi.org/10.1016/J.ADDR.2012.09.010
Hoare TR, Kohane DS (2008) Hydrogels in drug delivery: Progress and challenges. Polymer (Guildf) 49:1993–2007. https://doi.org/10.1016/J.POLYMER.2008.01.027
Bajpai SK, Sonkusley J (2002) Hydrogels for oral drug delivery of peptides: Synthesis and characterization. J Appl Polym Sci 83:1717–1729. https://doi.org/10.1002/app.10097
Tang X, Alavi S (2011) Recent advances in starch, polyvinyl alcohol based polymer blends, nanocomposites and their biodegradability. Carbohydr Polym 85:7–16. https://doi.org/10.1016/J.CARBPOL.2011.01.030
Ibrahim MM, El-Zawawy WK, Nassar MA (2010) Synthesis and characterization of polyvinyl alcohol/nanospherical cellulose particle films. Carbohydr Polym 79:694–699. https://doi.org/10.1016/J.CARBPOL.2009.09.030
Sinha Ray S, Bousmina M (2005) Biodegradable polymers and their layered silicate nanocomposites: In greening the 21st century materials world. Prog Mater Sci 50:962–1079. https://doi.org/10.1016/J.PMATSCI.2005.05.002
Majdzadeh-Ardakani K, Nazari B (2010) Improving the mechanical properties of thermoplastic starch/poly(vinyl alcohol)/clay nanocomposites. Compos Sci Technol 70:1557–1563. https://doi.org/10.1016/j.compscitech.2010.05.022
Liu Q, Chen N, Bai S, Li W (2018) Effect of silver nitrate on the thermal processability of poly(vinyl alcohol) modified by water. RSC Adv 8:2804–2810. https://doi.org/10.1039/C7RA12941F
Bueno VB, Bentini R, Catalani LH, Petri DFS (2013) Synthesis and swelling behavior of xanthan-based hydrogels. Carbohydr Polym 92:1091–1099. https://doi.org/10.1016/j.carbpol.2012.10.062
Shi R, Bi J, Zhang Z et al (2008) The effect of citric acid on the structural properties and cytotoxicity of the polyvinyl alcohol/starch films when molding at high temperature. Carbohydr Polym 74:763–770. https://doi.org/10.1016/j.carbpol.2008.04.045
Park H-R, Chough S-H, Yun Y-H, Yoon S-D (2005) Properties of Starch/PVA Blend Films Containing Citric Acid as Additive. J Polym Environ 13:375–382. https://doi.org/10.1007/s10924-005-5532-1
Das A, Uppaluri R, Das C (2019) Feasibility of poly-vinyl alcohol/starch/glycerol/citric acid composite films for wound dressing applications. Int J Biol Macromol 131:998–1007. https://doi.org/10.1016/j.ijbiomac.2019.03.160
Ounkaew A, Kasemsiri P, Kamwilaisak K et al (2018) Polyvinyl Alcohol (PVA)/Starch Bioactive Packaging Film Enriched with Antioxidants from Spent Coffee Ground and Citric Acid. J Polym Environ 26:3762–3772. https://doi.org/10.1007/s10924-018-1254-z
Wu Z, Wu J, Peng T et al (2017) Preparation and Application of Starch/Polyvinyl Alcohol/Citric Acid Ternary Blend Antimicrobial Functional Food Packaging Films. Polymers (Basel) 9:102. https://doi.org/10.3390/polym9030102
Chin SF, Romainor ANB, Pang SC, Lihan S (2019) Antimicrobial starch-citrate hydrogel for potential applications as drug delivery carriers. J Drug Deliv Sci Technol 54:101239. https://doi.org/10.1016/j.jddst.2019.101239
Sridach W, Jonjankiat S, Wittaya T (2013) Effect of citric acid, PVOH, and starch ratio on the properties of cross-linked poly(vinyl alcohol)/starch adhesives. J Adhes Sci Technol 27:1727–1738. https://doi.org/10.1080/01694243.2012.753394
Laçin NT (2014) Development of biodegradable antibacterial cellulose based hydrogel membranes for wound healing. Int J Biol Macromol 67:22–27. https://doi.org/10.1016/j.ijbiomac.2014.03.003
Bagri LP, Bajpai J, Bajpai AK (2011) Evaluation of starch based cryogels as potential biomaterials for controlled release of antibiotic drugs. Bull Mater Sci 34:1739–1748. https://doi.org/10.1007/s12034-011-0385-9
Korsmeyer RW, Gurny R, Doelker E et al (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
Higuchi T (1963) Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci 52:1145–1149. https://doi.org/10.1002/jps.2600521210
Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67:217–223
Mabrouk M, Mostafa AA, Oudadesse H et al (2014) Effect of ciprofloxacin incorporation in PVA and PVA bioactive glass composite scaffolds. Ceram Int 40:4833–4845. https://doi.org/10.1016/j.ceramint.2013.09.033
Pal K, Banthia AK, Majumdar DK (2008) Effect of heat treatment of starch on the properties of the starch hydrogels. Mater Lett 62:215–218. https://doi.org/10.1016/j.matlet.2007.04.113
Zou G-X, Qu J-P, Zou X-L (2007) Optimization of water absorption of starch/PVA composites. Polym Compos 28:674–679. https://doi.org/10.1002/pc.20333
Ghorpade VS, Dias RJ, Mali KK, Mulla SI (2019) Citric acid crosslinked carboxymethylcellulose-polyvinyl alcohol hydrogel films for extended release of water soluble basic drugs. J Drug Deliv Sci Technol 52:421–430. https://doi.org/10.1016/j.jddst.2019.05.013
Zhou X-H, Wei D-X, Ye H-M et al (2016) Development of poly(vinyl alcohol) porous scaffold with high strength and well ciprofloxacin release efficiency. Mater Sci Eng C 67:326–335. https://doi.org/10.1016/j.msec.2016.05.030
Sreedhar B, Sairam M, Chattopadhyay DK et al (2005) Thermal, mechanical, and surface characterization of starch-poly(vinyl alcohol) blends and borax-crosslinked films. J Appl Polym Sci 96:1313–1322. https://doi.org/10.1002/app.21439
Xu F, Lu T (2011) Experimental Characterization of Skin Biothermomechanics. Introduction to Skin Biothermomechanics and Thermal Pain. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 267–323
Mahdavinia GR, Karimi MH, Soltaniniya M, Massoumi B (2019) In vitro evaluation of sustained ciprofloxacin release from κ-carrageenan-crosslinked chitosan/hydroxyapatite hydrogel nanocomposites. Int J Biol Macromol 126:443–453. https://doi.org/10.1016/j.ijbiomac.2018.12.240
Ounkaew A, Kasemsiri P, Jetsrisuparb K et al (2020) Synthesis of nanocomposite hydrogel based carboxymethyl starch/polyvinyl alcohol/nanosilver for biomedical materials. Carbohydr Polym 248:116767. https://doi.org/10.1016/j.carbpol.2020.116767
Uliniuc A, Hamaide T, Popa M, Băcăiță S (2013) Modified Starch-Based Hydrogels Cross-Linked with Citric Acid and their use as Drug Delivery Systems for Levofloxacin. Soft Mater 11:483–493. https://doi.org/10.1080/1539445X.2012.710698
Marani PL, Bloisi GD, Petri DFS (2015) Hydroxypropylmethyl cellulose films crosslinked with citric acid for control release of nicotine. Cellulose 22:3907–3918. https://doi.org/10.1007/s10570-015-0757-1
Negi P, Singh B, Sharma G et al (2016) Phospholipid microemulsion-based hydrogel for enhanced topical delivery of lidocaine and prilocaine: QbD-based development and evaluation. Drug Deliv 23:941–957. https://doi.org/10.3109/10717544.2014.923067
Pang SC, Chin SF, Tay SH, Tchong FM (2011) Starch–maleate–polyvinyl alcohol hydrogels with controllable swelling behaviors. Carbohydr Polym 84:424–429. https://doi.org/10.1016/j.carbpol.2010.12.002
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David, J., Mahanty, B. Optimized ciprofloxacin release from citric acid crosslinked starch-PVA hydrogel film: modelling with mixture design. J Polym Res 28, 20 (2021). https://doi.org/10.1007/s10965-020-02397-7
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DOI: https://doi.org/10.1007/s10965-020-02397-7