Abstract
Silk fibroin/xanthan composite was investigated as a suitable biomedical material for controlled drug delivery, and blending ratios of silk fibroin and xanthan were optimized by response surface methodology (RSM) and artificial neural network (ANN) approach. A non-linear ANN model was developed to predict the effect of blending ratios, percentage swelling and porosity of composite material on cumulative percentage release. The efficiency of RSM was assessed against ANN and it was found that ANN is better in optimizing and modeling studies for the fabrication of the composite material. In-vitro release studies of the loaded drug chloramphenicol showed that the optimum composite scaffold was able to minimize burst release of drug and was followed by controlled release for 5 days. Mechanistic study of release revealed that the drug release process is diffusion controlled. Moreover, during tissue engineering application, investigation of release pattern of incorporated bioactive agent is beneficial to predict, control and monitor cellular response of growing tissues. This work also presented a novel insight into usage of various drug release model to predict material properties. Based on the goodness of fit of the model, Korsmeyer–Peppas was found to agree well with experimental drug release profile, which indicated that the fabricated material has swellable nature. The chloramphenicol (CHL) loaded scaffold showed better efficacy against gram positive and gram negative bacteria. CHL loaded SFX55 (50:50) scaffold shows promising biocomposite for drug delivery and tissue engineering applications.
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Koh L, Cheng Y, Teng C, Khin Y, Loh X, Tee S, et al. Structures, mechanical properties and applications of silk fibroin materials. Prog Polym Sci. 2015;46:86–110.
Li ZH, Ji SC, Wang YZ, Shen XC, Liang H. Silk fibroin-based scaffolds for tissue engineering. Front Mater Sci. 2013;7:237–47.
Nourmohammadi J, Roshanfar F, Farokhi M, Haghbin Nazarpak M. Silk fibroin/kappa-carrageenan composite scaffolds with enhanced biomimetic mineralization for bone regeneration applications. Mater Sci Eng C Mater Biol Appl. 2017;76:951–8.
Zhou J, Zhang B, Liu X, Shi L, Zhu J, Wei D, et al. Facile method to prepare silk fibroin/hyaluronic acid films for vascular endothelial growth factor release. Carbohydr Polym. 2016;143:301–9.
Li DW, Lei X, He FL, He J, Liu YL, Ye YJ, et al. International journal of biological macromolecules silk fibroin/chitosan scaffold with tunable properties and low inflammatory response assists the differentiation of bone marrow mesenchymal stem cells. Int J Biol Macromol. 2017;105:584–97.
Badwaik HR, Giri TK, Nakhate KT, Kashyap P, Tripathi DK. Xanthan gum and its derivatives as a potential bio-polymeric carrier for drug delivery system. Curr Drug Deliv. 2013;10:587–600.
Khan F, Tanaka M, Ahmad SR. Fabrication of polymeric biomaterials: a strategy for tissue engineering and medical devices. J Mater Chem B Mater Biol Med. 2015;3:8224–49.
Chamoli S. ANN and RSM approach for modeling and optimization of designing parameters for a V down perforated baffle roughened rectangular channel. Alexandria Eng J. 2015;54:429–46.
Zaki MR, Varshosaz J, Fathi M. Preparation of agar nanospheres: comparison of response surface and artificial neural network modeling by a genetic algorithm approach. Carbohydr Polym. 2015;122:314–20.
Gubskaya AV, Khan IJ, Valenzuela LM, Lisnyak YV, Kohn J. Investigating the release of a hydrophobic peptide from matrices of biodegradable polymers: an integrated method approach. Polymer (Guildf). 2013;54:3806–20.
McGinty S. A decade of modelling drug release from arterial stents. Math Biosci. 2014;257:80–90.
Arifin DY, Lee LY, Wang CH. Mathematical modeling and simulation of drug release from microspheres: implications to drug delivery systems. Adv Drug Deliv Rev. 2006;58:1274–325.
Abdulkhani A, Daliri Sousefi M, Ashori A, Ebrahimi G. Preparation and characterization of sodium carboxymethyl cellulose/silk fibroin/graphene oxide nanocomposite films. Polym Test. 2016;52:218–24.
Hu JX, Ran JB, Chen S, Jiang P, Shen XY, Tong H. Carboxylated Agarose (CA)-Silk Fibroin (SF) Dual Confluent Matrices Containing Oriented Hydroxyapatite (HA) Crystals: Biomimetic Organic/Inorganic Composites for Tibia Repair. Biomacromolecules. 2016;17:2437–47.
Kim UJ, Park J, Kim HJ, Wada M, Kaplan DL. Three-dimensional aqueous-derived biomaterial scaffolds from silk fibroin. Biomaterials. 2005;26:2775–85.
Muhsin MD, George G, Beagley K, Ferro V, Wang H, Islam N. Effects of chemical conjugation of l-leucine to chitosan on dispersibility and controlled release of drug from a nanoparticulate dry powder inhaler formulation. Mol Pharm. 2016;13:1455–66.
Vatankhah E, Semnani D, Prabhakaran MP, Tadayon M, Razavi S, Ramakrishna S. Artificial neural network for modeling the elastic modulus of electrospun polycaprolactone/gelatin scaffolds. Acta Biomater. 2014;10:709–21.
Bukzem AL, Signini R, Dos Santos DM, Lião LM, Ascheri DP. Optimization of carboxymethyl chitosan synthesis using response surface methodology and desirability function. Int J Biol Macromol. 2016;85:615–24.
Dwtest. http://in.mathworks.com/help/stats/dwtest.html. Accessed 12 May 2017.
Bukhari SMH, Khan S, Rehanullah M, Ranjha NM. Synthesis and characterization of chemically cross-linked acrylic acid/gelatin hydrogels: effect of pH and composition on swelling and drug release. Int J Polym Sci. 2015;2015:187961.
Takeno H, Kimura Y, Nakamura W. Mechanical, swelling, and structural properties of mechanically tough clay-sodium polyacrylate blend hydrogels. Gels. 2017;3:10.
Yadav AK, Malik H, Chandel SS. Selection of most relevant input parameters using WEKA for artificial neural network based solar radiation prediction models. Renew Sustain Energy Rev. 2014;31:509–19.
Singh P, Shera SS, Banik J, Banik RM. Optimization of cultural conditions using response surface methodology versus artificial neural network and modeling of l-glutaminase production by Bacillus cereus MTCC 1305. Bioresour Technol. 2013;137:261–9.
Cabezas LI, Gracia I, de Lucas A, Rodríguez JF. Novel model for the description of the controlled release of 5-fluorouracil from PLGA and PLA foamed scaffolds impregnated in supercritical CO2. Ind Eng Chem Res. 2014;53:15374–82.
Nayak AK, Pal D. Development of pH-sensitive tamarind seed polysaccharide-alginate composite beads for controlled diclofenac sodium delivery using response surface methodology. Int J Biol Macromol. 2011;49:784–93.
Perez RA, Shin SH, Han CM, Kim HW. Bioactive injectables based on calcium phosphates for hard tissues: a recent update. Tissue Eng Regen Med. 2015;12:143–53.
Carbinatto FM, de Castro AD, Evangelista RC, Cury BSF. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices. Asian J Pharm Sci. 2014;9:27–34.
Karuppuswamy P, Venugopal JR, Navaneethan B, Laiva AL, Ramakrishna S. Polycaprolactone nanofibers for the controlled release of tetracycline hydrochloride. Mater Lett. 2015;141:180–6.
Dash S, Murthy PN, Nath L, Chowdhury P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm. 2010;67:217–23.
Siepmann J, Peppas NA. Higuchi equation: derivation, applications, use and misuse. Int J Pharm. 2011;418:6–12.
Fu Y, Kao WJ. Drug release kinetics and transport mechanisms from semi-interpenetrating networks of gelatin and poly (ethylene glycol) diacrylate. Pharm Res. 2009;26:2115–24.
Siepmann J, Siepmann F. Fundamentals and Applications of Controlled Release Drug Delivery. In: Siepmann J, Siegel RA, Rathbone MJ, editors. Swelling controlled drug delivery system. Advances in delivery science and technology. New York: Springer; 2012. p. 153–70.
Bueno VB, Bentini R, Catalani LH, Petri DF. Synthesis and swelling behavior of xanthan-based hydrogels. Carbohydr Polym. 2013;92:1091–9.
Chung HJ, Min D, Kim JY, Lim ST. Effect of minor addition of xanthan on cross-linking of rice starches by dry heating with phosphate salts. J Appl Polym Sci. 2007;105:2280–6.
Chavda H, Patel C. Effect of crosslinker concentration on characteristics of superporous hydrogel. Int J Pharm Investig. 2011;1:17–21.
Klose D, Siepmann F, Elkharraz K, Krenzlin S, Siepmann J. How porosity and size affect the drug release mechanisms from PLGA-based microparticles. Int J Pharm. 2006;314:198–206.
Acknowledgements
The authors are grateful to School of Biochemical Engineering, Indian Institute of Technology (Banaras Hindu University) and Ministry of Human Resource and Development, Government of India, for providing financial support in terms of fellowship, research facilities, and infrastructure for carrying out the present research work.
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Shera, S.S., Sahu, S. & Banik, R.M. Preparation of Drug Eluting Natural Composite Scaffold Using Response Surface Methodology and Artificial Neural Network Approach. Tissue Eng Regen Med 15, 131–143 (2018). https://doi.org/10.1007/s13770-017-0100-z
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DOI: https://doi.org/10.1007/s13770-017-0100-z