Abstract
Amoxicillin is commonly used to treat a wide range of infections, but its use is limited by a relatively short biological half-life. This study developed a controlled-release amoxicillin nanoformulation and evaluated its antibacterial activity. The nanoparticles were synthesized by ionic gelation method assisted by sonication and characterized by Fourier transformed infrared, scanning electron microscopy and dynamic light scattering. The antibacterial effect was studied using micro-dilution method to determine the minimum inhibitory concentration of nanoparticles. Inhibition zone diameters of nanoformulation were also compared to those of the free amoxicillin. Sonication reduced the average size of nanoparticles by 70%. The encapsulation efficiency was 95 ± 2%. In vitro release studies showed the initial burst release in the first 10 h and continuous slow release up to the end. The antimicrobial results indicated that the amoxicillin-loaded chitosan nanoparticles were more effective than free amoxicillin against methicillin-susceptible- and methicillin-resistant forms of Staphylococcus aureus. The results highlight that the chitosan and sodium tripolyphosphate concentration and the sonication has a significant influence on nanoparticle size. The optimized chitosan nanoparticles with proper size and controlled release of β-lactam antibiotics may be a good candidate for treating antibiotic-resistant Staphylococcus aureus infections.
Similar content being viewed by others
References
Arora S, Gupta S, Narang RK, Budhiraja RD (2011) Amoxicillin loaded chitosan–alginate polyelectrolyte complex nanoparticles as mucopenetrating delivery system for H. pylori. Sci Pharm 79:673–694
Athar M, Das AJ (2014) Therapeutic nanoparticles: state-of-the-art of nanomedicine. Adv Mater Rev 1:25–37
Aydin R, Pulat M (2012) 5-Fluorouracil encapsulated chitosan nanoparticles for pH-stimulated drug delivery: evaluation of controlled release kinetics. J Nanomater 2012:42–52
Belal F, El-Kerdawy M, El-Ashry S, El-Wasseef D (2000) Kinetic spectrophotometric determination of ampicillin and amoxicillin in dosage forms. Farmaco 55:680–686
Calvo P, Remunan-Lopez C, Vila-Jato J, Alonso M (1997) Novel hydrophilic chitosan-polyethylene oxide nanoparticles as protein carriers. J Appl Polym Sci 63:125–132
Chattopadhyay D, Inamdar M (2012) Studies on synthesis, characterization and viscosity behaviour of nano chitosan. Res J Eng Sci 1:9–15
Cho H, Uehara T, Bernhardt TG (2014) Beta-lactam antibiotics induce a lethal malfunctioning of the bacterial cell wall synthesis machinery. Cell 159:1300–1311
Costelloe C, Metcalfe C, Lovering A, Mant D, Hay AD (2010) Effect of antibiotic prescribing in primary care on antimicrobial resistance in individual patients: systematic review and meta-analysis. BMJ 340:c2096
Dai T, Tanaka M, Huang YY, Hamblin MR (2011) Chitosan preparations for wounds and burns: antimicrobial and wound-healing effects. Expert Rev Anti Infect Ther 9:857–879
David MZ, Daum RS (2010) Community-associated methicillin-resistant Staphylococcus aureus: epidemiology and clinical consequences of an emerging epidemic. Clin Microbiol Rev 23:616–687
Elzoghby AO, Samy WM, Elgindy NA (2012) Albumin-based nanoparticles as potential controlled release drug delivery systems. J Control Rel 157:168–182
Esmaeilzadeh-Gharedaghi E, Faramarzi MA, Amini MA, Rouholamini Najafabadi A, Rezayat SM, Amani A (2012) Effects of processing parameters on particle size of ultrasound prepared chitosan nanoparticles: an Artificial Neural Networks Study. Pharm Dev Technol 17:638–647
Farokhzad OC, Langer R (2009) Impact of nanotechnology on drug delivery. ACS Nano 3:16–20
Floris A, Meloni MC, Lai F, Marongiu F, Maccioni AM, Sinico C (2013) Cavitation effect on chitosan nanoparticle size: a possible approach to protect drugs from ultrasonic stress. Carbohydr Polym 94:619–625
Gao P, Nie X, Zou M, Shi Y, Cheng G (2011) Recent advances in materials for extended-release antibiotic delivery system. J Antibiot (Tokyo) 64:625–634
Gibot L, Chabaud S, Bouhout S, Bolduc S, Auger FA, Moulin VJ (2015) Anticancer properties of chitosan on human melanoma are cell line dependent. Int J Biol Macromol 72:370–379
Gresser U (2001) Amoxicillin-clavulanic acid therapy may be associated with severe side effects-review of the literature. Eur J Med 6:139–149
He C, Hu Y, Yin L, Tang C, Yin C (2010) Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials 31:3657–3666
Höltje JV (1995) From growth to autolysis: the murein hydrolases in Escherichia coli. Arch Microbiol 164:243–254
Jayakumar R, Menon D, Manzoor K, Nair S, Tamura H (2010) Biomedical applications of chitin and chitosan based nanomaterials—a short review. Carbohydr Polym 82:227–232
Ji J, Hao S, Wu D, Huang R, Xu Y (2011) Preparation, characterization and in vitro release of chitosan nanoparticles loaded with gentamicin and salicylic acid. Carbohydr Polym 85:803–808
Klein E (2007) Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999–2005. Emerg Infect Dis 13:1840–1846
Kulkarni SA, Feng SS (2013) Effects of particle size and surface modification on cellular uptake and biodistribution of polymeric nanoparticles for drug delivery. Pharm Res 30:2512–2522
Kumar MNR (2000) A review of chitin and chitosan applications. React Funct Polym 46:1–27
Kumar D, Dharmendra S, Jhansee M, Shrikant N, Pandey SP (2011) Development and characterization of chitosan nanoparticles loaded with amoxicillin. Int Res J Phar 2:145–511
Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces 75:1–18
Pandey R, Zahoor A, Sharma S, Khuller G (2003) Nanoparticle encapsulated antitubercular drugs as a potential oral drug delivery system against murine tuberculosis. Tuberculosis 83:373–378
Portero A, Remunan-Lopez C, Criado M, Alonso M (2002) Reacetylated chitosan microspheres for controlled delivery of anti-microbial agents to the gastric mucosa. J Microencapsul 19:797–809
Qi L, Xu Z, Jiang X, Hu C, Zou X (2004) Preparation and antibacterial activity of chitosan nanoparticles. Carbohydr Res 339:2693–2700
Rinaudo M (2006) Chitin and chitosan: properties and applications. Prog Polym Sci 31:603–632
Sarwar A, Katas H, Zin NM (2014) Antibacterial effects of chitosan–tripolyphosphate nanoparticles: impact of particle size molecular weight. J Nanopart Res 16:1–14
Tavares W (2000) Problem Gram-positive bacteria: resistance in staphylococci, enterococci, and pneumococci to antimicrobial drugs. Rev Soc Bras Med Trop 33:281–301
Tiyaboonchai W (2003) Chitosan nanoparticles: a promising system for drug delivery. Naresuan Univ J 11:51–66
Yen MT, Yang JH, Mau JL (2008) Antioxidant properties of chitosan from crab shells. Carbohydr Polym 74:840–844
Younes I, Rinaudo M (2015) Chitin and chitosan preparation from marine sources. Structure properties and applications. Mar Drugs 13:1133–1174
Zagari RM, Bianchi-Porro G, Fiocca R, Gasbarrini G, Roda E, Bazzoli F (2007) Comparison of 1 and 2 weeks of omeprazole, amoxicillin and clarithromycin treatment for Helicobacter pylori eradication: the HYPER Study. Gut 56:475–479
Acknowledgements
Financial assistance from Iran National Science Foundation (INSF), Grant no. 94014310 is gratefully acknowledged. The authors sincerely thank Mrs. Zahra Zahedi for help with the DLS experiments.
Author information
Authors and Affiliations
Contributions
MH contributed in conception of the work, study design, conducting the study, manuscript preparation, revising the draft, approval of the final version of the manuscript, and agreed for all aspects of the work. AT contributed in conception of the work, conducting the study, data analysis, revising the draft, approval of the final version of the manuscript, and agreed for all aspects of the work.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Hadizadeh, M., Toraji, A. Amoxicillin-Loaded Polymeric Nanoparticles of Less than 100 nm: Design, Preparation and Antimicrobial Activity Against Methicillin-Resistant Staphylococcus aureus. Iran J Sci Technol Trans Sci 43, 379–386 (2019). https://doi.org/10.1007/s40995-017-0346-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40995-017-0346-2