Optimization of Poly(methyl vinyl ether-co-maleic acid) Electrospun Nanofibers as a Fast-Dissolving Drug Delivery System

Document Type : Original Article

Authors

1 Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Biotechnology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Poly(methyl vinyl ether-maleic acid) (PMVEMA) is a water-soluble, biodegradable polymer used for drug delivery. The aim of the present study was to prepare nanofibers of this polymer as a fast-dissolving carrier for montelukast. Materials and Methods: Polymeric nanofibers were spun by electrospinning method using different ratios of biodegradable polymer of PMVEMA. The processing variables including voltage, distance of the needle to rotating screen, and flow rate of the solution were optimized based on the diameter of the nanofibers, drug content, and release efficiency by a Taguchi design. The morphology, diameter, and diameter distribution of the nanofibers were studied by scanning electron microscopy (SEM). Drug loading and its release rate from the nanofibers were analyzed spectrophotometrically. The possible molecular between the polymer and the drug was characterized with Fourier-transform-infrared spectroscopy. Results: The results showed the best situation for electrospinning of the polymer obtained at the polymer concentration of 37%, the distance of the needle to rotating screen of 19 cm, the voltage of 120 kV, and the rate of injection of 0.2 ml/h. In these situations, the fiber diameter and drug loading efficiency percentage were 273 nm and 83%, respectively. These nanofibers released the total loaded drug within 1–3 s with no residue in the dissolution medium. SEM results showed that the optimized nanofibers were quite smooth and without beads. Conclusions: The results indicated that the nanofibers of PMVEMA could dissolve the drug very rapidly and can be adopted for fast-dissolving dosage forms.

Keywords

1.
Elizondo E, Córdoba A, Sala S, Ventosa N, Veciana J. Preparation of biodegradable poly (methyl vinyl ether-co-maleic anhydride) nanostructured microparticles by precipitation with a compressed antisolvent. J Supercrit Fluids 2010;53:108-14.  Back to cited text no. 1
    
2.
Popescu I, Suflet DM, Pelin IM, Chiţanu GC. Biomedical applications of maleic anhydride copolymers. Rev Roum Chim 2011;56:173-88.  Back to cited text no. 2
    
3.
Wang Y, Chang F, Zhang Y, Liu N, Liu G, Gupta S, et al. Pretargeting with amplification using polymeric peptide nucleic acid. Bioconjug Chem 2001;12:807-16.  Back to cited text no. 3
[PUBMED]    
4.
Varshosaz J, Minaiyan M, Forghanian M. Prolonged hypocalcemic effect by pulmonary delivery of calcitonin loaded poly(methyl vinyl ether maleic acid) bioadhesive nanoparticles. Biomed Res Int 2014;2014:932615.  Back to cited text no. 4
[PUBMED]    
5.
Ali MS, Vijendar C, Sudheer Kumar D, Krishnaveni J. Formulation and evaluation of fast dissolving oral films of diazepam. J Pharmacovigil 2016;4:2329-6887.  Back to cited text no. 5
    
6.
Mahajan A. Formulation & evaluation of fast dissolving buccal films of sertraline. Int J Drug Dev Res 2012;4:220-6.  Back to cited text no. 6
    
7.
Kim SB, Lee JH, Lee J, Shin SH, Eun HS, Lee SM, et al. The efficacy and safety of montelukast sodium in the prevention of bronchopulmonary dysplasia. Korean J Pediatr 2015;58:347-53.  Back to cited text no. 7
[PUBMED]    
8.
Sarasija S, Pandit V, Joshi HP. Preparation and evaluation of mouth dissolving tablets of salbutamol sulphate. Indian J Pharm Sci 2007;69:467-9.  Back to cited text no. 8
    
9.
Khatoon N, Raghavendra Rao NG, Reddy BM. Formulation and evaluation of oral fast dissolving films of montelukast sodium. Int J Pharm Sci Res 2014;5:1780-7.  Back to cited text no. 9
    
10.
Jannesari M, Varshosaz J, Morshed M, Zamani M. Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs. Int J Nanomedicine 2011;6:993-1003.  Back to cited text no. 10
[PUBMED]    
11.
Li X, Kanjwal MA, Lin L, Chronakis IS. Electrospun polyvinyl-alcohol nanofibers as oral fast-dissolving delivery system of caffeine and riboflavin. Colloids Surf B Biointerfaces 2013;103:182-8.  Back to cited text no. 11
[PUBMED]    
12.
Illangakoon UE, Gill H, Shearman GC, Parhizkar M, Mahalingam S, Chatterton NP, et al. Fast dissolving paracetamol/caffeine nanofibers prepared by electrospinning. Int J Pharm 2014;477:369-79.  Back to cited text no. 12
[PUBMED]    
13.
Wu YH, Yu DG, Li XY, Diao AH, Illangakoon UE, Williams GR. Fast-dissolving sweet sedative nanofiber membranes. J Mater Sci 2015;50:3604-13.  Back to cited text no. 13
    
14.
Sill TJ, von Recum HA. Electrospinning: Applications in drug delivery and tissue engineering. Biomaterials 2008;29:1989-2006.  Back to cited text no. 14
[PUBMED]    
15.
Zamani M, Morshed M, Varshosaz J, Jannesari M. Controlled release of metronidazole benzoate from poly epsilon-caprolactone electrospun nanofibers for periodontal diseases. Eur J Pharm Biopharm 2010;75:179-85.  Back to cited text no. 15
[PUBMED]    
16.
Luu YK, Kim K, Hsiao BS, Chu B, Hadjiargyrou M. Development of a nanostructured DNA delivery scaffold via electrospinning of PLGA and PLA-PEG block copolymers. J Control Release 2003;89:341-53.  Back to cited text no. 16
[PUBMED]    
17.
Lee JY, Bashur CA, Goldstein AS, Schmidt CE. Polypyrrole-coated electrospun PLGA nanofibers for neural tissue applications. Biomaterials 2009;30:4325-35.  Back to cited text no. 17
[PUBMED]    
18.
Hsu CM, Shivkumar S. N, N-Dimethylformamide additions to the solution for the electrospinning of poly(e-caprolactone) nanofibers. Macromol Mater Eng 2004;289:334-40.  Back to cited text no. 18
    
19.
Deitzel JM, Kleinmeyer J, Harris D, Tan NC. The effect of processing variables on the morphology of electrospun nanofibers and textiles. Polymer 2001;42:261-72.  Back to cited text no. 19
    
20.
Meechaisue C, Dubin R, Supaphol P, Hoven VP, Kohn J. Electrospun mat of tyrosine-derived polycarbonate fibers for potential use as tissue scaffolding material. J Biomater Sci Polym Ed 2006;17:1039-56.  Back to cited text no. 20
[PUBMED]    
21.
Zhao S, Wu X, Wang L, Huang Y. Electrospinning of ethyl-cyanoethyl cellulose/tetrahydrofuran solutions. J Appl Polym Sci 2004;91:242-6.  Back to cited text no. 21
    
22.
Taylor G. Electrically driven jets. Proc Natl Acad Sci London 1969;313:453-75.  Back to cited text no. 22
    
23.
Megelski S, Stephens JS, Chase DB, Rabolt JF. Micro- and nanostructured surface morphology on electrospun polymer fibers. Macromolecules 2002;35:8456-66.  Back to cited text no. 23
    
24.
Doshi J, Reneker DH. Electrospinning process and applications of electrospun fibers. J Electrostat 1995;35:151-60.  Back to cited text no. 24
    
25.
Jaeger R, Bergshoef MM, Batlle CM, Schonherr H, Vancso GJ. Electrospinning of ultra-thin polymer fibers. Macromol Symp 1998;127:141-50.  Back to cited text no. 25
    
26.
Ramakrishna S, Fujihara K, Teo WE, Lim TC, Ma Z. An Introduction to Electrospinning and Nanofibers. Singapore: World Scientific; 2005. p. 978-81.  Back to cited text no. 26
    
27.
Mit-uppatham C, Nithitanakul M, Supaphol P. Ultrafine electrospun polyamide-6 fibers: Effect of solution conditions on morphology and average fiber diameter. Macromol Chem Phys 2004;205:2327-38.  Back to cited text no. 27