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Recent Patents on Drug Delivery & Formulation


ISSN (Print): 1872-2113
ISSN (Online): 2212-4039

Review Article

Nanoantibiotic Formulations to Combat Antibiotic Resistance - Old Wine in a New Bottle

Author(s): Rachna Rana, Rajendra Awasthi*, Bhupesh Sharma and Giriraj T. Kulkarni

Volume 13 , Issue 3 , 2019

Page: [174 - 183] Pages: 10

DOI: 10.2174/1872211313666190911124626


Antibiotic resistance is becoming one of the major obstacles to treatment success in various pathological conditions. Development process of a new antimicrobial agent is slow and difficult, whereas bacterial resistance is decreasing the arsenal of existing antibiotics. Therefore, there is a need to develop novel antibiotic formulations to combat the resistance of existing antibiotics. Nanoparticles are investigated as novel antibiotic formulation, but are often inefficient in practical applications. Nanotechnology presents a new frontier to overcome the issue of antibiotic resistance through the development of functionalized particles. Balance of physicochemical characteristics such as small particle size and high drug loading capacity along with improved stability are the challenges associated with large scale manufacturing of nanoantibiotic formulations. In the last 1-2 decades, a gradual increase in patents on nanoantibiotic formulations has been noted to address the resistance issues of antibiotic. The aim of this review is to consolidate recently-investigated nanoantibiotic formulations to combat antibiotic resistance.

Keywords: Antibiotic resistance, drug resistance, infectious diseases, infection, public health, bacterial resistance.

Graphical Abstract
Qiao M, Ying GG, Singer AC, Zhu YG. Review of antibiotic resistance in China and its environment. Environ Int 2018; 110: 160-72.
[] [PMID: 29107352]
Dyson ZA, Klemm EJ, Palmer S, Dougan G. Antibiotic resistance and typhoid. Clin Infect Dis 2019; 68(2): S165-70.
[] [PMID: 30845331]
Armstrong GL, Conn LA, Pinner RW. Trends in infectious disease mortality in the United States during the 20th century. JAMA 1999; 281(1): 61-6.
[] [PMID: 9892452]
Alanis AJ. Resistance to antibiotics: Are we in the post-antibiotic era? Arch Med Res 2005; 36(6): 697-705.
[] [PMID: 16216651]
Cohen ML. Changing patterns of infectious disease. Nature 2000; 406(6797): 762-7.
[] [PMID: 10963605]
Kunin CM. Clinical pharmacology of the new penicillins. 1. The importance of serum protein binding in determining antimicrobial activity and concentration in serum. Clin Pharmacol Ther 1966; 7(2): 166-79.
[] [PMID: 4956690]
Brown ED, Wright GD. Antibacterial drug discovery in the resistance era. Nature 2016; 529(7586): 336-43.
[] [PMID: 26791724]
Bradley M, Nealeigh M, Oh JS, Rothberg P, Elster EA, Rich NM. Combat casualty care and lessons learned from the past 100 years of war. Curr Probl Surg 2017; 54(6): 315-51.
[] [PMID: 28595716]
Schmieder R, Edwards R. Insights into antibiotic resistance through metagenomic approaches. Future Microbiol 2012; 7(1): 73-89.
[] [PMID: 22191448]
Salyers AA, Gupta A, Wang Y. Human intestinal bacteria as reservoirs for antibiotic resistance genes. Trends Microbiol 2004; 12(9): 412-6.
[] [PMID: 15337162]
Martínez JL. Antibiotics and antibiotic resistance genes in natural environments. Science 2008; 321(5887): 365-7.
[] [PMID: 18635792]
WHO. Global action plan on antimicrobial resistance 2015. [Last accessed on 2019 March 13
Huh AJ, Kwon YJ. “Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era. J Control Release 2011; 156(2): 128-45.
[] [PMID: 21763369]
Ovais M, Zia N, Khalil AT, Ayaz M, Khalil A, Ahmad I. Nanoantibiotics: Recent developments and future prospects. Frontiers in Clinical Drug Research-Anti Infectives 2019; 5: 158.
WHO fact sheet. Antimicrobial resistance. Available from: Accessed on 22.07 2019
D.A. Approved Drugs. Center Watch Available from: [Last accessed on 2019 March 16
Newton BA. Mechanisms of antibiotic action. Annu Rev Microbiol 1965; 19(1): 209-40.
[] [PMID: 5318438]
Tenover FC. Mechanisms of antimicrobial resistance in bacteria. Am J Med 2006; 119(6): S3-S10.
[] [PMID: 16735149]
Davies J, Davies D. Origins and evolution of antibiotic resistance. Microbiol Mol Biol Rev 2010; 74(3): 417-33.
[] [PMID: 20805405]
Annavajhala MK, Gomez-Simmonds A, Uhlemann AC. Multidrug-resistant Enterobacter cloacae complex emerging as a global, diversifying threat. Front Microbiol 2019; 10: 44.
[] [PMID: 30766518]
Sawatwong P, Sapchookul P, Whistler T, et al. High burden of extended-spectrum β-lactamase-producing Escherichia coli and klebsiella pneumoniae bacteremia in older adults: A seven-year study in two rural Thai provinces. Am J Trop Med Hyg 2019; 100(4): 943-51.
[] [PMID: 30793684]
World Health Organization. Antibiotic Resistance- Fact Sheet; 2018. Available from: [Last accessed on 2019 March 08]
Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 2015; 13(1): 42-51.
[] [PMID: 25435309]
Levy SB. The challenge of antibiotic resistance. Sci Am 1998; 278(3): 46-53.
[] [PMID: 9487702]
Hardwick SA, Stokes HW, Findlay S, Taylor M, Gillings MR. Quantification of class 1 integron abundance in natural environments using real-time quantitative PCR. FEMS Microbiol Lett 2008; 278(2): 207-12.
[] [PMID: 18042230]
Teixeira MC, Sanchez-Lopez E, Espina M, et al. Advances in antibiotic nanotherapy: Overcoming antimicrobial resistance. Emerging Nanotechnol Immunol 2018; 2018: 233-59.
Hayat S, Fakhar-E-Alam M, Aslam B, et al. Nanoantibiotics: Future nanotechnologies to combat antibiotic resistance. Front Biosci 2018; 10: 352-74.
Ali K, Dwivedi S, Azam A, et al. Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multi-drug resistant clinical bacterial isolates. J Colloid Interface Sci 2016; 472: 145-56.
[] [PMID: 27031596]
Hao N, Chen X, Jeon S, Yan M. Carbohydrate‐Conjugated hollow oblate mesoporous silica nanoparticles as nanoantibiotics to target mycobacteria. Adv Healthc Mater 2015; 4(18): 2797-801.
[] [PMID: 26450697]
Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Ismail M, Webster TJ. Synthesis, characterization, controlled release, and antibacterial studies of a novel streptomycin chitosan magnetic nanoantibiotic. Int J Nanomedicine 2014; 9: 549-57.
[PMID: 24549109]
Hussein-Al-Ali SH, El Zowalaty ME, Hussein MZ, Geilich BM, Webster TJ. Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications. Int J Nanomedicine 2014; 9: 3801-14.
[] [PMID: 25143729]
Jun SH, Cha SH, Kim JH, Yoon M, Cho S, Park Y. Silver nanoparticles synthesized using Caesalpinia sappan extract as potential novel nanoantibiotics against methicillin-resistant Staphylococcus aureus. J Nanosci Nanotechnol 2015; 15(8): 5543-52.
[] [PMID: 26369115]
Kalhapure RS, Jadhav M, Rambharose S, et al. pH-responsive chitosan nanoparticles from a novel twin-chain anionic amphiphile for controlled and targeted delivery of vancomycin. Colloids Surf B Biointerfaces 2017; 158: 650-7.
[] [PMID: 28763772]
Pedraza D, Díez J, Colilla M, Vallet-Regí M. Amine-functionalized mesoporous silica nanoparticles: A new nanoantibiotic for bone infection treatment. Biomedical Glasses 2018; 4(1): 1-2.
Saidykhan L, Abu Bakar MZ, Rukayadi Y, Kura AU, Latifah SY. Development of nanoantibiotic delivery system using cockle shell-derived aragonite nanoparticles for treatment of osteomyelitis. Int J Nanomedicine 2016; 11: 661-73.
[] [PMID: 26929622]
Emmanuel R, Saravanan M, Ovais M, Padmavathy S, Shinwari ZK, Prakash P. Antimicrobial efficacy of drug blended biosynthesized colloidal gold nanoparticles from Justicia glauca against oral pathogens: A nanoantibiotic approach. Microb Pathog 2017; 113: 295-302.
[] [PMID: 29101061]
Maruthupandy M, Rajivgandhi G, Muneeswaran T, Song JM, Manoharan N. Biologically synthesized zinc oxide nanoparticles as nanoantibiotics against ESBLs producing gram negative bacteria. Microb Pathog 2018; 121: 224-31.
[] [PMID: 29807135]
Xie Y, Liu Y, Yang J, et al. Gold nanoclusters for targeting methicillin-resistant Staphylococcus aureus in vivo. Angew Chem Int Ed Engl 2018; 57(15): 3958-62.
[] [PMID: 29423995]
Khurana C, Chudasama B. Nanoantibiotics: Strategic assets in the fight against drug-resistant superbugs. Int J Nanomedicine 2018; 13: 3.
Kalhapure RS, Mocktar C, Sikwal DR, et al. Ion pairing with linoleic acid simultaneously enhances encapsulation efficiency and antibacterial activity of vancomycin in solid lipid nanoparticles. Colloids Surf B Biointerfaces 2014; 117: 303-11.
[] [PMID: 24667076]
Kumar PS. MubarakAli D, Saratale RG, Saratale GD, Pugazhendhi A, Gopalakrishnan K, Thajuddin N. Synthesis of nano-cuboidal gold particles for effective antimicrobial property against clinical human pathogens. Microb Pathog 2017; 113: 68-73.
Pender DS, Vangala LM, Badwaik VD, Thompson H, Paripelly R, Dakshinamurthy R. A New class of gold nanoantibiotics - Direct coating of ampicillin on gold nanoparticles. Pharm Nanotechnol 2013; 1(2): 126-35.
Omolo CA, Kalhapure RS, Jadhav M, et al. Pegylated oleic acid: A promising amphiphilic polymer for nano-antibiotic delivery. Eur J Pharm Biopharm 2017; 112: 96-108.
[] [PMID: 27890573]
Saxena V, Hasan A, Sharma S, Pandey LM. Edible oil nanoemulsion: An organic nanoantibiotic as a potential biomolecule delivery vehicle. Int J Polym Mater Polym Biomat 2018; 67(7): 410-9.
Sikwal DR, Kalhapure RS, Rambharose S, et al. Polyelectrolyte complex of vancomycin as a nanoantibiotic: Preparation, in vitro and in silico studies. Mater Sci Eng C 2016; 63: 489-98.
[] [PMID: 27040243]
Tripathy N, Ahmad R, Bang SH, Min J, Hahn YB. Tailored lysozyme-ZnO nanoparticle conjugates as nanoantibiotics. Chem Commun (Camb) 2014; 50(66): 9298-301.
[] [PMID: 25000144]
Siemer S, Westmeier D, Vallet C, et al. Breaking resistance to nanoantibiotics by overriding corona-dependent inhibition using a pH-switch. Mater Today 2019; 26: 19-29.
Singh BN, Prateeksha CV, Rawat AK, Upreti DK, Singh BR. Antimicrobial nanotechnologies: What are the current possibilities? Curr Sci 2015; 108(7): 1210.
Chan WS, Tang BS, Boost MV, Chow C, Leung PH. Detection of methicillin-resistant Staphylococcus aureus using a gold nanoparticle-based colourimetric polymerase chain reaction assay. Biosens Bioelectron 2014; 53: 105-11.
[] [PMID: 24125759]
Van Giau V, An SSA, Hulme J. Recent advances in the treatment of pathogenic infections using antibiotics and nano-drug delivery vehicles. Drug Des Devel Ther 2019; 13: 327-43.
[] [PMID: 30705582]
Leet JE, Helen A, Donald RG, et al. Nocathiacin antibiotics. US6218398B1 (2001)
Hughes D, Ling LL, Nitti A, Peoples AJ, Spoering A. Novel macrocyclic antibiotics and uses thereof. WO/2017/147003A1 (2017)
Kwon YJ, Edson J. Stimuli-responsive polysaccharide antimicrobial agents. WO/2019/014389 (2019)
Day D, John NZ. Anti-microbial combination. WO/2018/185735 (2018)
Qiu S, Wang G. Method for preparing antibiosis (coating) film. CN1563156 (2005)
Suvimol S, Jakrawan Y, Katawut N, et al. Uracha, R., Nattika, S., Teerapong, Y., Nitwarat, R., Pattapong, K., Kanokkan, N. method for preparing nano-particle of tilmicosin and product thereof. WO/2019/032057 (2019)
Kwon YJ. Polymeric antibiotics. US9889204 (2018)
Kwon YJ. Polymeric antibiotics. US15847492 (2018)
Mosqueira VC, Araujo RS, de Mello BH. Nanoparticulate composition containing antibiotics for intramammary administration in animals. EP2578209A1 (2013)
Yeoman RR, Winchurch RA. Targeted therapeutic nanoparticles. US9694085B2 (2017)
Clinical trials. CenterWatch. Available from: [Last accessed on 2019 August 13]
Maurya A, Singh AK, Mishra G, et al. Strategic use of nanotechnology in drug targeting and its consequences on human health: A focused review. Interv Med Appl Sci 2019; 11: 38-54.

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