"The new generation of antibiotics"
Published on: Mar 3, 2016
Transcripts - Nano Antibiotics
“Nanoantibiotics”: A new paradigm for
treating infectious diseases using
nanomaterials in the antibiotics resistant
N. MOHAMED FAIZEE
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
These NPs retained in our body longer time for achieving sustained
It is the ability of microorganisms to withstand the effects of an antibiotic.
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
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.
Nanotechnology for Identifying Infection
It is new method for identifying and preventing the growth of pathogenic
Toxic shock syndrome(TSS) is a serious disease caused by a toxin produced
by Staphylococcus aureus bacteria. It occurs during skin infection, burns,
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.
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.
The researchers have demonstrated the effectiveness of their system for two
pathogenic species of bacteria, P. aeruginosa and S. aureus.
Mechanism of Nanoantibiotics
Enhanced Antibacterial Activity
of Nanocrystalline ZnO
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
The stability is due to Particle size, shape and surface area, Electronic states
such as valence and conductance states.
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.
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%
Results and Discussion
X-ray diffraction patterns of ZnO NPs
The average crystallite size, Debye-
L - Average crystallite size (nm)
λ - X-ray wavelength (nm)
β - full width at half maximum (FWHM)
θ - Bragg angle of the plane 15
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
TEM images ZnO NPs
HR-TEM images ZnO NPs
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.
Antibacterial activity of ZnO against E. coli
and S. aureus
Antibacterial Test against S. aureus
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 destroying the cell
S. aureus with Large Sized NPs
Antibacterial Test against E.coli
E. coli Cell with two NucleoidsUntreated E. coli Cells
Inhibition Test for E. coli
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 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.
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.
Entrapment or Encapsulation
During the 1970, scientists first began to encapsulate and entrap drugs within
Encapsulation involves surrounding drug molecules with a solid polymer shell.
Entrapment involves the suspension of drug molecules within a polymer matrix.
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
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
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
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
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
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.
Drug Release of Cisplatin & DOX
Cisplatin and DOX in Ovarian Cells
Advantages and disadvantages of antimicrobial
NPs over free antimicrobial agents
Antimicrobial NPs :
• 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
• High systemic exposure to locally administrated drugs
• Nanotoxicity (lung, kidney, liver, brain, germ cell, metabolic, etc.)
• Lack of characterization techniques.
Free antimicrobial agents
No specific accumulation
High side effects of chemical antimicrobials
High antimicrobial resistance
Short half life due to fast elimination
Absence of NPs in the whole body
Absence of nanotoxicity
Well-established characterization techniques
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
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