Kapita Selekta: Nanosystems

and Antimicrobial
Applications

apt. Oktavia Eka Puspita, S.Farm., M.Sc.

Sistem Pengantaran Bentuk Sediaan Obat
Semester Genap TA. 2020/2021
Nanosystems and antibacterial
applications
 • Increased prevalence of antibiotic resistance among
Latar Belakang bacteria is a major reason for the urgency in
development of new antibacterial agents.
• Antibiotic resistance is the capacity of bacteria that
cause disease to resist the actions of antibiotics, which
is one of the greatest threats to human health according
to World Health Organisation
• In order to understand antibacterial applications of
nanosystems, it is important to know how bacteria lead
to colonization and infection and evade existing
antibacterial therapies.
• two forms of bacterial growth include a free living existence that are not adhered to a surface called planktonic
growth, and a sessile state that form communities, called biofilm growth.
• Biofilms are responsible for more than two-thirds of microbial infections in humans and are up to 1000 times more
resistant to antibacterial treatments compared to their planktonic equivalents
▪ Biofilms typically constitute a dense and
hydrated (up to 97% water content) group of
bacteria.
▪ Such structured but complex biofilm
communities consist of one or more species of
bacteria bonded to one another, to a substrate,
and surrounded in an extracellular matrix
consisting mainly of exopolysaccharide,
proteins, and extracellular DNA
▪ A growing number of infections
such as pneumonia, tuberculosis,
and gonorrhoea are becoming
difficult to treat as the antibiotics
used to treat them become less
effective.
▪ Antibiotic resistance leads to
longer hospital stays, higher
medical costs, and increased
mortality rates.
▪ It kills an estimated 700,000 people
each year worldwide.
 Discovery!
▪ In the past four decades, the only antibiotic with
an entirely novel mechanism of action that has
been developed is linezolid and the future looks
challenging with the exception of the recently
discovered teixobactin.
▪ antibiotics now produces only very few viable
antibacterial compounds.
▪ The human and economic cost of antibiotic
resistance is massive and if neglected,
antimicrobial resistance could lead to 10 million
deaths worldwide by 2050
Nanosystems untuk • nanoparticle-based
Antibakteri • targeted specifically and to reach therapeutic intracellular
levels
• sustained release depending on environmental conditions
• optimize the physicochemical characteristics of drugs,
allowing their clinical use or administration through more
patient-friendly routes
diffusion and interaction of antibacterial
agents with the biofilm matrix

Understanding the mechanism of multidrug

tolerance among biofilm bacteria and the
presence of persistent cells, a protected
subpopulation of bacteria, are a crucial
threat for novel nanosystem development.

Because of the variation and unknown

resistant mechanisms possessed by
biofilms, novel combat strategies such
as nanosystems should be developed to
control bacterial infections.
The use of antibacterial drug-carrying
nanosystems was found to exert drug
efficacy by overcoming resistance
mechanisms that include:
▪ drug degradation by β-lactamase,
▪ efflux pumps,
▪ Gram-positive bacterial cell walls
that contain thick layer of
peptidoglycan
▪ In the human gastrointestinal tract,
Helicobacter pylori is a prominent infective
bacteria but its treatment is hampered by
inability of certain drugs to cross the gastric
epithelial surface and reach the intercellular
bacterium.
▪ However, use of some nanosystems helped to
evade these problems with its mucoadhesive
properties of interacting with mucin and
infiltration to cell-cell junctions to reach H.
pylori .
▪ P. aeruginosa and its antibiotic
resistant strains are common in
cystic fibrosis patients, causing
almost 90% of mortality.
▪ Currently, different types of
nanosystems are pursued to
improve comfortable administration
routes, better dosage schedules and
efficacy in treating cystic fibrosis
patients
 • overall surface properties of bacteria that play a crucial role in
Antibacterial Nanosystems Poses bacterial attachment
Many Challenges
• hydrophobicity in relation to both bulk liquid and the nanosystems
has been demonstrated to influence bacterial attachment
• surface hydrophobicity are thought to result from the net surface
properties convened upon the cell surface molecules like lipids and
proteins
• certain bacteria are known to possess an intrinsic ability to alter
their surface hydrophobicity in ways that would either promote or
hinder attachment to a nanosystem
• Nanosystem interactions with proteins of the blood, tissues or
mucosa and with the cellular membrane depend on the charge and
the zeta (ζ)-potential, affecting both uptake by cells and
biodistribution.
• Host cells such as macrophages present a negatively charged
surface so that cationic nanosystems would undergo better uptake
than neutral or negatively charged ones in vivo
• Like zeta (ζ)-potential, hydrophobicity is also key in targeted drug
delivery from nanosystems; an increase of hydrophobicity is known
to decrease the diffusion kinetic in mucus and favors cellular
uptake, owing to interactions with the lipids of the cell membrane.
• These properties thus influence nanosystem output from
endosomes and subsequent drug release from them to the target.
More crucially, nanosystems with a hydrophilic nature display low
interactions with opsonins and the complement system making
their clearance from the blood slower when compared with
hydrophobic nanosystems.
Nanosystem Untuk • Organic nanosystems include liposomes, solid lipid
Antibakteri nanosystems, polymeric micelles, and polymeric
nanosystems.
• Major challenges posed by these nanosystems include
lowloading efficacy and drug loss during storage
• Nanosystems based on liposomes are major source for
antibacterial application with formulations, Ambisome,
already in commercial applications
▪ One of the most common manufacturing
techniques in industries is the extrusion method.
▪ Liposomes are prepared prior to the extrusion
procedure by a simple process of dissolving the
lipid component in an organic solvent before
emulsifying this mixture in an aqueous phase and
slowly evaporating the organic solvent.
▪ The liposomes formed are then, in their liquid-
crystalline state, extruded through polycarbonate
filters with defined pore sizes using pressurised
N2 gas at temperatures above the phase transition
temperature
Figure 2. Forming unilamellar liposomes of the defined size by extrusion through a
defined pore membrane filter. (A) Schematic representation of the extrusion process.
(B) Graph reflecting uniformity of size via repeated passages of the liposomes through
the membrane.
▪ The production of a sterile preparation using this
method is possible if pore sizes of 200 nm are used.
▪ However, for most of the other manufacturing
techniques, terminal sterilization is still required and
the susceptibility of the liposomes to various chemical
and physical degradation mechanisms has rendered
conventional sterilisation techniques unsuitable.
▪ Some of the main degradation pathways include
oxidation, hydrolysis, phase transition and
aggregation.
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