Design and optimization of metformin released from ZnO/Chitosan nanocomposite

Document Type : Original Research

Authors

Shahryar Branch, Islamic Azad University

Abstract
Metformin enhances insulin's effect and increases cells’ sensitivity to insulin. In this paper, nanocomposite was designed and used in the metformin release system, which was able to release the required drug in a controlled manner. In this research, nanoparticles of zinc oxide (ZnO) were prepared via the sol-gel method. The experimental design central composite response surface method was applied for the optimization of the nanoparticles based on varied variables such as the weight of zinc acetate (gr) (X 1) and the volume of triethanolamine (ml) (X2). The particle size of the optimized nanoparticle was reported to be 28 ± 21.27 nm; zeta potential and PdI were 25.54 ± 1.64 mV, 0.168 ± 0.05 respectively. The chitosan polymer was used to improve environmental compatibility and increase drug release control; finally, metformin was loaded on the optimized nanocomposite. Structural properties were analyzed using scanning electron microscopy (SEM) X-Ray Diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and Dynamic Light Scattering (DLS). The SEM images showed that the average nanocomposite size was 40 nm. The results of XRD patterns and SEM images were also consistent with each other and the average particle size was the same. Infrared spectrophotometry showed the presence of chitosan used to coat nanoparticles on their surfaces and confirmed the loading of metformin. An in-vitro metformin release from the nanocomposite was conducted in PBS (pH=7.4) and analyzed by a spectrophotometer at 233 nm. Metformin has a high solubility in water, and since it is difficult to prepare a slow release form of high-solubility drugs, the aim of this study was to design a slow-release formulation of metformin with a suitable profile that could control release without explosive release for up to 120 hours.

Keywords

Subjects


[1] Mausam, M.و D, Allen-Gipsona., Shyam, M., Mark, Kindya., Alya, L. Study on the therapeutic index and synergistic effect of Chitosan-zinc oxide nanomicellar composites for drug-resistant bacterial biofilm inhibition. Int. J. Pharm. 2019. 565, 472–480.
[2] Sadhukhan, P.; Kundu, M.; Chatterjee, S.; Ghosh, N.; Manna, P.; Das, J.; Sil, P.C. Targeted delivery of quercetin via pH-responsive zinc oxide nanoparticles for breast cancer therapy. MAT SCI ENG C-MATER. 2019, 100, 129-140.
[3] Boateng, J. S.; Matthews, K. H.; Stevens, H. N.; Eccleston, G. M. Wound healing dressings and drug delivery systems: a review. J. Pharm. Sci. 2008, 97, 2892-2923.
[4] Khorasani M.T., Joorabloo A., Adeli H., Mansoori-Moghadam Z., Moghaddam A. Design and optimization of process parameters of polyvinyl (alcohol)/chitosan/nano zinc oxide hydrogels as wound healing materials, Carbohydr polym, 207, 542-554, 2019.
[5] Samad A., Sultana Y., Aqil M. Liposomal drug delivery systems: an update review. Curr drug deliv, 4, 297-305, 2007.
[6] Arora S., Ali J., Ahuja A., Khar R. K., Baboota S. Floating drug delivery systems: a review. Aps Pharm Sci Tech, 6, 372-390, 2015.
[7] Sun C., Lee J. S., Zhang M. Magnetic nanoparticles in MR imaging and drug delivery. Adv. drug deliv. Rev, 60, 1252-1265, 2008.
[8] Schmaljohann D. Thermo-and pH-responsive polymers in drug delivery. Adv. drug deliv. Rev, 58, 1655-1670, 2006.
[9] Sastry S. V., Nyshadham J. R., Fix J. A. Recent technological advances in oral drug delivery–a review. Pharm sci& tech today, 3, 138-145, 2000.
[10] Slowing I. I., Vivero-Escoto J. L., Wu C. W., Lin V. S. Y. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv. drug deliv. Rev, 60, 1278-1288, 2008.
[11] Gahlawat G., Choudhury A. R. A review on the biosynthesis of metal and metal salt nanoparticles by microbes. RSC Adv, 9, 12944-12967, 2019.
[12] Reddy C. V., Reddy K. R., Shetti N. P., Shim J., Aminabhavi T. M., Dionysiou D. Hetero-nanostructured metal oxide-based hybrid photocatalysts for enhanced photoelectrochemical water splitting–A review. INT J HYDROGEN ENERG, 36, 1-17, 2019.
[13] Ong C. B., Ng L. Y., Mohammad A. W. A review of ZnO nanoparticles as solar photocatalysts: synthesis, mechanisms and applications. RENEW SUST ENERG REV, 81, 536-551, 2018.
[14] Amjadi S., Emaminia S., Davudian S.H., Pourmohammad S., Hamishehkar H. ,Roufegarinejad L. Preparation and characterization of gelatin-based nanocomposite containing chitosan nanofiber and ZnO nanoparticles. Carbohydr polym, 216, 376-384, 2019.
[15] García-González C. A., Alnaief M., Smirnova I. Polysaccharide-based aerogels—Promising biodegradable carriers for drug delivery systems. Carbohydrate Polymers, 86, 1425-1438, 2011.
[16] Ghosh P., Han G., De M., Kim C. K., Rotello V. M. Gold nanoparticles in delivery applications. Adv. drug deliv. Rev, 60, 1307-1315, 2008.
[17] Mehta M., Allen-Gipson D., Mohapatra S., Kindy M., Limayem A. Study on the therapeutic index and synergistic effect of Chitosan-zinc oxide nanomicellar composites for drug-resistant bacterial biofilm inhibition. Int. J.Pharm, 565, 472-480, 2019.
[18] Bhattarai N., Gunn J., Zhang M. Chitosan-based hydrogels for controlled, localized drug delivery. Adv. drug deliv. Rev, 62, 83-99, 2010.
[19] Ashour A. H., El-Batal A. I., Maksoud M. A., El-Sayyad G. S., Labib S., Abdeltwab E., El-Okr M. Antimicrobial activity of metal-substituted cobalt ferrite nanoparticles synthesized by sol–gel technique. Particuology, 40, 141-151, 2018.
[20] Omri K., El Ghoul J., Lemine O.M., Bououdina M., Zhang B., El Mir L. Magnetic and optical properties of manganese doped ZnO nanoparticles synthesized by sol–gel technique. SUPERLATTICE MICROST, 60, 139-147, 2013.
[21] Veith M., Haas M., Huch V. Single source precursor approach for the sol− gel synthesis of nanocrystalline ZnFe2O4 and zinc− iron oxide composites. Chem. Mater, 17, 95-101, 2005.
[22] Hasnidawani J. N., Azlina H. N., Norita H., Bonnia N. N., Ratim S., Ali E. S. Synthesis of ZnO nanostructures using sol-gel method. Procedia Chem, 19, 211-216, 2016.
[23] Dananjaya S. H. S., Kumar R. S., Yang M., Nikapitiya C., Lee J., De Zoysa M. Synthesis, characterization of ZnO-chitosan nanocomposites and evaluation of its antifungal activity against pathogenic Candida albicans. Int. J. Biol. Macromol, 108, 1281-1288, 2018.
[24] Cahyana A. H., Fitria D., Ardiansah B., Rahayu D. U. C. Preparation of Fe3O4/SiO2-guanidine organobase catalyst for 1, 5-diphenylpenta-2, 4-dien-1-one synthesis. Mater. Sci. Eng, 188, 1-6, 2017.
[25] Suganthi K.S., Rajan K.S. Temperature induced changes in ZnO–water nanofluid: zeta potential, size distribution and viscosity profiles. Int. J. Heat Mass Transf, 55, 7969-7980, 2012.
[26] Shahsavari, Sh., Vasheghani-Farahani, E., Ardjmand, M., Abedin Dorkoosh, F. Design and Characterization of Acyclovir Loaded Nanoparticles for Controlled Delivery System. Current. Nano. 10, 521-531, 2014.
[27] Nava O. J.,Luque P. A., Gomez-Gutierrez C. M., Vilchis-Nestor A. R., Castro-Beltran A., Mota-Gonzalez M. L., Olivas A. Influence of Camellia sinensis extract on Zinc Oxide nanoparticle green synthesis. J. Mol. Struct, 1134, 121-125, 2017.
[28] Li L. H., Deng J. C., Deng H. R., Liu Z. L., Xin L. Synthesis and characterization of chitosan/ZnO nanoparticle composite membranes. Carbohydr. Res, 345, 994-998, 2010.
[29] Das A., Nikhil S. K., Nair R. G. Influence of surface morphology on photocatalytic performance of zinc oxide: A review. Nano-Struct & Nano-Obj, 19, 100353, 2019.
[30] Carvalho V. V., Gonçalves J. O., Silva A., Cadaval T. R., Pinto L. A., Lopes T. J. Separation of anthocyanins extracted from red cabbage by adsorption onto chitosan films. Int. J. Biol. Macromol, 131, 905-911, 2019.
[31] Yang J., Dahlström C., Edlund H., Lindman B., Norgren, M. pH-responsive cellulose–chitosan nanocomposite films with slow release of chitosan. Cellulose, 26, 3763-3776, 2019.
[32] Ganesh M., Ubaidulla U., Rathnam G., Jang H. T. Chitosan-telmisartan polymeric cocrystals for improving oral absorption: In vitro and in vivo evaluation. Int. J. Biol. Macromol, 131, 879-885, 2019.
[33] Divya K., Rana D., Alwarappan S., Saraswathi M. S., Nagendran A. Investigating the usefulness of chitosan based proton exchange membranes tailored with exfoliated molybdenum disulfide nanosheets for clean energy applications. Carbohydr polym, 208, 504-512, 2019.
[34] Panda B. P. Impact of statistical central composite face centered design approach on method and process optimization of metformin hydrochloride loaded PLGA nanoformulation. Micro. Nano. Sys, 9, 55-71, 2017.