Pharmaceutical

Nanotechnology
Lec#4, Kareem Ebeid, Ph.D.
Assistant Professor of Pharmaceutics, Minia University
Minia, Egypt

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Antibody conjugates:
• Antibodies can also function as carriers for drugs and other
agents, including radioisotopes.
• These antibody conjugates are sometimes referred to as
immunoconjugates.
• By conjugation of a molecule to an appropriate
monoclonal antibody, the molecules actively target the
drug to the required site of action.
• ProstaScint®: Monoclonal antbody against PSMA
conjugate to indium 111 (radiolabeled antibody).

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Dendrimers:
• Dendrimers are highly branched polymeric, starshaped macromolecules
which can be prepared in the nanosize range. Dendrimers are built by a
controlled chemical synthesis.
• By varying the construction of the dendrimer around
the core unit, one can build dendrimers of different
shapes and sizes, which can offer the ability to carry
drugs within the construct, or one can conjugate
drugs to the surface of the dendrimer.
• The surface of the dendrimer can also be modified
with targeting groups, or a hydrophilic coating to
enhance solubility.
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Dendrimers:
• These branched polymeric structures are synthesized by stepwise addition
of layers of polymer branching, referred to as generations (termed G1, G2,
etc.). In general, as the number of layers or generations increases, the
structure of the dendrimer moves from the open structures of the low-
generation dendrimer to an increasingly more globular and dense
structure.

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Dendrimers:

• In all cases, the resulting constructs are built to have a specific size, a high
degree of molecular uniformity and a narrow molecular weight
distribution.
• Whilst dendrimers can be considered as an evolution of branched
polymers, they offer the advantage that they can be prepared with a very
narrow size distribution.
• Furthermore, the large number of peripheral groups on the exterior surface
of the dendrimer, which increase exponentially with each generation
added, allows higher drug-loading capacities compared with the linear or
branched polymers used in polymer–drug conjugates 5
Applications of Dendrimers:

• Same as those of polymer drug conjugate.

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Micelle systems:

• Micelles are used to formulate low-solubility drugs in colloidal solutions.

• Micelles form because of the ability of surfactant molecules to self-
assemble into micelles in an aqueous environment.
• Their size (often <100 nm) means that micelles can be considered within
the nanotechnology classification.
• As a consequence of the micellar structure, which offers a hydrophobic
core and a hydrophilic surface, micelles are commonly used as solubilizing
agents. For example, Fugizone® is a mixed micellar formulation which is
used to solubilize amphotericin B, an antifungal agent. 7
Micelle systems: Polymeric micelles
• Copolymers with surfactant characteristics can also be used to formulate
micelles.
• Polymeric micelles have a lower critical micelle concentration (CMC) and
are more stable.
• Because of their low CMCs, polymeric micelles are relatively insensitive to
dilution, thus preventing their rapid dissociation and enhancing their
systemic circulation time compared with surfactant micelles.

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Micelle systems: Polymeric micelles
• Polymeric micelles are built from copolymers with hydrophobic components :
• poly(propylene oxide),
• poly(D,L-lactic acid),
• poly(ε-caprolactone),
• poloxamers.
• For the hydrophilic component, which forms the outer hydrophilic shell of
• the micelle, PEG is commonly used.
• The use of PEG as the hydrophilic component supports the formation of the
micelles.

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Micelle systems: Polymeric micelles
• The hydrated PEG surface created on the micelles enhances their plasma
half-life by promoting steric hindrance and blocking enzymes and antibodies
from reaching the drug, thereby offering protection to the drug, and
blocking interactions with the MPS.
• As the micelles are sufficiently large (> 50 kDa) to avoid renal excretion yet
small enough (< 200 nm) to avoid clearance by the liver and spleen, they are
able to specifically accumulate at tumour sites and sites of inflammation
because of passive targeting.

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Micelle systems: Polymeric micelles: Case Study

• Genexol®-PM. This is a polymeric micelle formulation of paclitaxel prepared

with PEG–poly(D,L-lactide) which is approved in South Korea for treatment of
metastatic breast cancer.
• In vivo antitumour efficacy of the micellar formulation has been shown to be
significantly higher than that of Taxol®.

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Solid Nanoparticles:

• Solid nanoparticles are solid constructs in the nanometer range, and can be
prepared by a number of different manufacturing methods which generally
Involve:
1. size reduction of particles (e.g. by milling) to within the nanoparticle
range (prepare drug particles in the nanosize range where there is no
carrier material added)
2. Molecular agglomeration (e.g. by precipitation methods) to form
nanoparticles (It is more commonly used to prepare nanoparticle carriers
in which drug is loaded).
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Solid Nanoparticles:

1. size reduction of particles (e.g. by milling)

2. Molecular agglomeration (e.g. by precipitation methods)

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Solid Nanoparticles: 1- Nanocrystals

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Solid Nanoparticles: 1- Nanocrystals

Powdered Drug Drug Nanocrystals

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Solid Nanoparticles: 1- Nanocrystals

• Reducing the size of drug particles to within the nanosize range substantially
increases the total surface area of the system, hence increasing the solubility
of the drug.
• This attribute can be exploited to increase the dissolution ability and
bioavailability of drugs delivered by the oral route.
• The use of nanosized drug particles in oral drug delivery can also avoid
variations in drug bioavailability caused by the fed/fasted state of a patient.

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Solid Nanoparticles: 1- Nanocrystals

• Nanosized drug particles, owing to their high surface area and subsequent
high interfacial energy, tend to be unstable and prone to particle
aggregation.
• To reduce this problem, surface-active agents can be used.
• Nanocrystals are prepared from 100% drug, and stabilizers (surfactants) are
added during the size-reduction process to increase stability

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Solid Nanoparticles: 1- Nanocrystals
• Nanosized drug particles, owing to their high surface area and subsequent
high interfacial energy, tend to be unstable and prone to particle
aggregation.
• To reduce this problem, surface-active agents can be used.
• Nanocrystals are prepared from 100% drug, and stabilizers (surfactants) are
added during the size-reduction process to increase stability.
• For oral delivery, nanocrystals are normally formulated into tablets or
capsules.
• With these systems, a key consideration is drug loading, as a high nanocrystal
loading in tablets could result in contact between nanocrystals, promoting
potential fusion of the crystals during tablet compression. 18
Solid Nanoparticles: 1- Nanocrystals

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Solid Nanoparticles: 1- Nanocrystals

Megace® ES contains 625 mg of megestrol acetate per 5 mL

whereas Megace® oral suspension and other megestrol acetate
oral suspensions contain 800 mg per 20 mL

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Thank You