“Nanoantibiotics”: A new paradigm for
treating infectious diseases using
nanomaterials in the antibiotics resistant
era
By...
NanoAntibiotics
 The Nano Particles (NPs) are physical attracted to the infected cells by
breaking their walls without de...
Antibiotic Resistance
 It is the ability of microorganisms to withstand the effects of an antibiotic.
3
Limitations of Current Antibiotics
 Use of antibiotics started with production of penicillin in 1942s after that
many new...
 FDA approval for new antibiotics also become less in each year due to
ineffectiveness against bacteria.
 For this disco...
Nanotechnology for Identifying Infection
 It is new method for identifying and preventing the growth of pathogenic
bacter...
 This smart wound dressing system that only releases an encapsulated
antimicrobial agent in the presence of pathogenic ba...
 The researchers have demonstrated the effectiveness of their system for two
pathogenic species of bacteria, P. aeruginos...
Mechanism of Nanoantibiotics
9
Enhanced Antibacterial Activity
of Nanocrystalline ZnO
10
Introduction
 Nanosized inorganic particles, exhibit unique physical, chemical, and
biological properties. Metal oxides i...
Preparation of ZnO NPs
 ZnO NPs is produced by an sonication method . An appropriate ultrasonic
energy is required to ind...
 Different types of ZnO NPs were prepared,
 Zinc oxide with 10% water- DMF
 Zinc oxide with water, and
 Commercial Zin...
Results and Discussion
14
X-ray diffraction patterns of ZnO NPs
The average crystallite size, Debye-
Scherrer formula,


cos
89.0
L
L - Average ...
 In XRD pattern,
a (ZnO-3) = Commercial zinc oxide sample,
b (ZnO-2) = Zinc oxide with water sample,
c (ZnO-1) = Zinc oxi...
TEM images ZnO NPs
17
HR-TEM images ZnO NPs
18
 The ZnO in water NPs are mostly monodispersed but they form network
structure which shows that particle is synthesized i...
Antibacterial activity of ZnO against E. coli
and S. aureus
20
Antibacterial Test against S. aureus
21
Effect of Zinc oxide with 10%
water- DMF sample
Untreated S. aureus Cells
 Due to the large sized nanoparticles, ZnO NPs were not able to
penetrate the cell, ROS activity is observed and destroyi...
Antibacterial Test against E.coli
23
E. coli Cell with two NucleoidsUntreated E. coli Cells
Inhibition Test for E. coli
24
Without ZnO NPs Effect of Zinc oxide with 10%
water- DMF sample
 By using the sonochemical method smaller sized NPs is obtained, which
shows an enhanced antibacterial activity.
 The mo...
NPs in Drug Delivery
 Targeted drug delivery: Delivering a drug to a specific site in the body
where it has the greatest ...
Entrapment or Encapsulation
 During the 1970, scientists first began to encapsulate and entrap drugs within
polymers.
 E...
Drug Release by Diffusion
 Early encapsulation and entrapment systems released the drug from within the
polymer via molec...
Targeting Cancer with a Triple Threat
 The first polymer NPs that carry a defined ratio of three cancer drugs and
release...
Mechanism of Drug Release
 There is no limitation on how many drugs you can add, and the ratio of
drugs carried by the pa...
31
Drugs Ratio
32
Drug Release of Cisplatin & DOX
33
Cisplatin and DOX in Ovarian Cells
Advantages and disadvantages of antimicrobial
NPs over free antimicrobial agents
Antimicrobial NPs :
 Advantage:
• Target...
Free antimicrobial agents
 Disadvantage
 No specific accumulation
 High side effects of chemical antimicrobials
 High ...
Conclusion
 Antibiotics have been saving an enormous number of lives from many
infectious diseases, but due to the effect...
References
 [1] Ae Jung Huh, Young Jik Kwon, Journal of Controlled Release 156
(2011) 128–145.
 [2] Guy Applerot, Anat L...
The Next
Generation of
Antibiotics
of 38

Nano Antibiotics

"The new generation of antibiotics"
Published on: Mar 3, 2016
Published in: Technology      
Source: www.slideshare.net


Transcripts - Nano Antibiotics

  • 1. “Nanoantibiotics”: A new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era By N. MOHAMED FAIZEE 13-PCH-19 1
  • 2. NanoAntibiotics  The Nano Particles (NPs) are physical attracted to the infected cells by breaking their walls without destroying the healthy cells around them.  Various nano sized drug carriers are efficiently involved in improving pharmacokinetics and accumulation which will reduce adverse effect of antibiotics.  These NPs retained in our body longer time for achieving sustained therapeutic effects. 2
  • 3. Antibiotic Resistance  It is the ability of microorganisms to withstand the effects of an antibiotic. 3
  • 4. Limitations of Current Antibiotics  Use of antibiotics started with production of penicillin in 1942s after that many new antibiotics were developed.  Evolving of microorganisms creating infectious diseases and antimicrobial resistance against the new antibiotics.  Some bacteria are untreatable by the antibiotics such as vancomycin- resistant S. aureus (VRSA) and methicillin-resistant S. aureus (MRSA).  Because their spores are highly resistant and very thick harder to enter the drug inside the cell and not affected by antibiotics.  This shows that treating this virulent bacteria with antibiotics is extremely difficult. 4
  • 5.  FDA approval for new antibiotics also become less in each year due to ineffectiveness against bacteria.  For this discovery and delivery of antimicrobial drugs with improved efficacy, and avoidance of resistance are highly demanded.  These limitations leads to Nanotechnology in immunization, for controlling infectious diseases and overcoming antibiotic resistant pathogens. 5
  • 6. Nanotechnology for Identifying Infection  It is new method for identifying and preventing the growth of pathogenic bacteria.  Toxic shock syndrome(TSS) is a serious disease caused by a toxin produced by Staphylococcus aureus bacteria. It occurs during skin infection, burns, wound infection.  For that Scientist from University of Bath, UK created an advanced wound dressing that can detect the key bacteria causing TSS.  This new material can automatically detect infection by pathogenic bacteria and respond to this by releasing an antibiotic into the wound. 6
  • 7.  This smart wound dressing system that only releases an encapsulated antimicrobial agent in the presence of pathogenic bacteria, without responding to harmless bacteria.  Nanocapsules which releases an dye when it detects and kill the bacteria and give the colour under UV light. 7
  • 8.  The researchers have demonstrated the effectiveness of their system for two pathogenic species of bacteria, P. aeruginosa and S. aureus. 8
  • 9. Mechanism of Nanoantibiotics 9
  • 10. Enhanced Antibacterial Activity of Nanocrystalline ZnO 10
  • 11. Introduction  Nanosized inorganic particles, exhibit unique physical, chemical, and biological properties. Metal oxides in nanometer sized shows their electromagnetic, optical and catalytic properties.  Normally, metal oxides NPs are synthesized by chemical methods, but there by sonochemical technique is used for synthesizing crystalline NPs.  Organic antibacterial agents have limited their application, such as low heat resistance, high decomposability and short life.  Inorganic antibacterial agents are thermally stable and longer lasting, chemically durable and effective against a bacteria / fungi and even cancer cells.  The stability is due to Particle size, shape and surface area, Electronic states such as valence and conductance states. 11
  • 12. Preparation of ZnO NPs  ZnO NPs is produced by an sonication method . An appropriate ultrasonic energy is required to induce collapsing gas bubbles which agitate the particles with high temperature.  The implosive collapse of the bubbles generates a localized hot spots of extremely high temperature and high pressure powerful ultrasound radiation (20 kHz) and having high cooling rates responsible for crystal formation. .  The sonochemical method is advantageous as it is nonhazardous, rapid in reaction rate and produces very small metal particles. 12
  • 13.  Different types of ZnO NPs were prepared,  Zinc oxide with 10% water- DMF  Zinc oxide with water, and  Commercial Zinc oxide.  In this 10% water–DMF solution reaction gives a better yield than with water alone that is due DMF, which generated a smaller nanoparticles and a more uniform crystal growth.  The product yields with water and water–DMF were 56% and 73% respectively. 13
  • 14. Results and Discussion 14
  • 15. X-ray diffraction patterns of ZnO NPs The average crystallite size, Debye- Scherrer formula,   cos 89.0 L L - Average crystallite size (nm) λ - X-ray wavelength (nm) β - full width at half maximum (FWHM) θ - Bragg angle of the plane 15
  • 16.  In XRD pattern, a (ZnO-3) = Commercial zinc oxide sample, b (ZnO-2) = Zinc oxide with water sample, c (ZnO-1) = Zinc oxide with 10% water- DMF sample.  Here ZnO samples synthesized in the water–DMF medium, the peaks obtained were more line-broadened due to the small nanometer-scale crystal size. 16
  • 17. TEM images ZnO NPs 17
  • 18. HR-TEM images ZnO NPs 18
  • 19.  The ZnO in water NPs are mostly monodispersed but they form network structure which shows that particle is synthesized in the water medium.  It shows that it has a stronger tendency to aggregate and to form soft agglomerates in the aqueous medium due to that interparticle interactions will be generated.  But these interactions are reduced in the 10% water–DMF solution, due to the capping of the particles by the DMF. 19
  • 20. Antibacterial activity of ZnO against E. coli and S. aureus 20
  • 21. Antibacterial Test against S. aureus 21 Effect of Zinc oxide with 10% water- DMF sample Untreated S. aureus Cells
  • 22.  Due to the large sized nanoparticles, ZnO NPs were not able to penetrate the cell, ROS activity is observed and destroying the cell membrane. 22 S. aureus with Large Sized NPs
  • 23. Antibacterial Test against E.coli 23 E. coli Cell with two NucleoidsUntreated E. coli Cells
  • 24. Inhibition Test for E. coli 24 Without ZnO NPs Effect of Zinc oxide with 10% water- DMF sample
  • 25.  By using the sonochemical method smaller sized NPs is obtained, which shows an enhanced antibacterial activity.  The more efficient antibacterial activity against E. coli and S. aureus is due using smaller sized NPs.  These smaller NPs shown more cellular internalization observed in TEM, and percentage of reduction in viability seen in antibacterial test.  Between these two bacteria, E. coli was affected more than S. aureus due to weaker antioxidant in cell which shows less resistant to OS, and having thin peptidoglycan cell wall for easy penetration by NPs. 25
  • 26. NPs in Drug Delivery  Targeted drug delivery: Delivering a drug to a specific site in the body where it has the greatest effect, instead allowing it to diffuse to various sites which may cause damage or side effects.  Controlled drug delivery: Which delivers the drug at a predetermined rate, by systematically at specified period of time.  The nanoparticles are effective for drug delivery, it find the diseased cells very precisely and carry the medicine to that place. By using less dosage and thereby fewer side effects.  In that polymeric NPs have very high surface areas, drugs may also be adsorbed on their surface. Their nanometer-size promotes effective permeation through cell membranes and stability in the blood stream. 26
  • 27. Entrapment or Encapsulation  During the 1970, scientists first began to encapsulate and entrap drugs within polymers.  Encapsulation involves surrounding drug molecules with a solid polymer shell.  Entrapment involves the suspension of drug molecules within a polymer matrix. drug polymer Drug Polymer
  • 28. Drug Release by Diffusion  Early encapsulation and entrapment systems released the drug from within the polymer via molecular diffusion.  When the polymer absorbs water it swells in size,  Swelling created voids throughout the interior polymer,  Smaller molecule drugs can escape via the voids at a known rate controlled by molecular diffusion (a function of temperature and drug size). Add water Add time
  • 29. Targeting Cancer with a Triple Threat  The first polymer NPs that carry a defined ratio of three cancer drugs and release them with three independent triggering mechanisms against Ovarian cancers.  Doxorubicin, camptothecin, and cisplatin are a standard combination therapy for aggressive ovarian cancers.  Instead of attaching drugs to NPs, they synthesized NPs from drug-containing building blocks. In two building blocks, the researchers linked doxorubicin or camptothecin to a norbornene monomer (along with a protective PEG group).  In a third unit, they inserted cisplatin between two norbornene monomers to form a cross-linking agent. By the new method of ring-opening metathesis polymerization (ROMP). 29
  • 30. Mechanism of Drug Release  There is no limitation on how many drugs you can add, and the ratio of drugs carried by the particles just depends on in the beginning how they are mixed together.  Each particle carries the three drugs in a specific ratio that matches the maximum tolerated dose of each drug, and each drug has its own release mechanism.  Cisplatin is freed as soon as the particle enters a cell, as the bonds holding it to the particle break down on exposure to glutathione. Camptothecin is also released quickly when it encounters cellular enzymes called esterases.  The third drug, doxorubicin, it would be released only when ultraviolet light shines on the particle. Once all three drugs are released, the left behind is PEG, which is easily biodegradable. 30
  • 31. 31
  • 32. Drugs Ratio 32
  • 33. Drug Release of Cisplatin & DOX 33 Cisplatin and DOX in Ovarian Cells
  • 34. Advantages and disadvantages of antimicrobial NPs over free antimicrobial agents Antimicrobial NPs :  Advantage: • Targeted drug delivery via specific accumulation • Lowered side effects of chemical antimicrobials • Extended therapeutic lifetime due to slow elimination • Controlled drug release • Broad therapeutic index • Low cost  Disadvantage: • High systemic exposure to locally administrated drugs • Nanotoxicity (lung, kidney, liver, brain, germ cell, metabolic, etc.) • Lack of characterization techniques. 34
  • 35. Free antimicrobial agents  Disadvantage  No specific accumulation  High side effects of chemical antimicrobials  High antimicrobial resistance  Short half life due to fast elimination  Poor solubility  High cost  Advantage  Absence of NPs in the whole body  Absence of nanotoxicity  Well-established characterization techniques 35
  • 36. Conclusion  Antibiotics have been saving an enormous number of lives from many infectious diseases, but due to the effect antibiotic resistance by microbes more powerful antibiotics is needed.  For that nanotechnology helping in many ways through nanodevices, detecting bacteria by NPs, targeted and controlled drug delivery by NPs and enhanced antibacterial activities by NPs.  These are possible due to high surface area to volume ratio and unique physico-chemical properties exhibited by NPs.  NPs prevent drugs from interacting with normal cells, thus avoiding side effects. 36
  • 37. References  [1] Ae Jung Huh, Young Jik Kwon, Journal of Controlled Release 156 (2011) 128–145.  [2] Guy Applerot, Anat Lipovsky, Rachel Dror, Nina Perkas, Yeshayahu Nitzan, Rachel Lubart, and Aharon Gedanken*, Adv. Funct. Mater. 2009, 19, 842–852.  [3] Muhammad Ali Syed and S. Habib Ali Bukhari∗ J. Biomed. Nanotechnol. 2011, Vol. 7, No. 2.  [4] Charalambos Kaittanis, Santimukul Santra, and J. Manuel Perez, Adv Drug Deliv Rev. 2010 March 18; 62(4-5): 408–423.  [5] Longyan Liao, Jenny Liu,Erik C. Dreaden, Stephen W. Morton, Kevin E. Shopsowitz, Paula T. Hammond, and Jeremiah A. Johnson, J. Am. Chem. Soc. 2014, 136, 5896−5899. 37
  • 38. The Next Generation of Antibiotics

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