nano-particles and targeting strategies in drug delivery

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K.GAUTHAM REDDY 2011A8PS364G NANOPARTICLES IN DRUG DELIVERY

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Page 1: Nano-particles and targeting strategies in drug delivery

K . G A U T H A M R E D D Y2 0 1 1 A 8 P S 3 6 4 G

NANOPARTICLES IN DRUG DELIVERY

Page 2: Nano-particles and targeting strategies in drug delivery

INTRODUCTION

Various nanoforms have been attempted as drug delivery systems

Biological substances - albumin, gelatin and phospholipids for liposomes.

Chemical substances - Superparamagnetic NPs and solid metal-containing NPs

Page 3: Nano-particles and targeting strategies in drug delivery

ORGANIC NANOPLATFORMS

Liposomes Liposomes are self-assembled artificial vesicles

developed from amphiphilic phospholipids.  The ability to entrap both hydrophilic and

hydrophobic drugsBiocompatibility, Biodegradability Advantage: Liposome properties, such as size,

surface charge and functionality, can be easily tuned through the addition of agents to the lipid membrane .

Page 4: Nano-particles and targeting strategies in drug delivery
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Polymer NP

Polymeric NPs are colloidal particles with a size range of 10–1000 nm

 Fabricated using biodegradable synthetic polymers, such as polycaprolactones or natural polymers, such as albumin, gelatin

Methods : solvent evaporation, spontaneous emulsification, solvent diffusion etc have been used to prepare the NPs.

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Smart polymer NP

Stimuli-sensitive polymer which can change its physicochemical properties in response to environmental signals.

Physical (temperature, ultrasound, light, electricity and mechanical stress), chemical (pH and ionic strength) and biological signals (enzymes and biomolecules)

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copolymers answering multiple stimuli

Advantage: High sensitivity in response to a given stimulus within a narrow range, leading to more accurate in drug delivery.

Page 8: Nano-particles and targeting strategies in drug delivery

INORGANIC PLATFORMS

Super paramagnetic nanoparticles

The superparamagnetic NP are used to guide microcapsules in place for delivery by external magnetic fields.

Another advantage of using magnetic NPs is the ability to heat the particles after internalization, which is known as the hyperthermia effect.

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Super paramagnetic nanoparticles in controlled drug delivery

Affect the permeability of microcapsules by applying external oscillating magnetic fields and releasing encapsulated materials

Controlled release of substances by applying an external magnetic field.

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Integrated nanocomposite particles

Each type of nanoparticle has unique advantages and limitations.

By combining the specific function of each material, new hybrid nanocomposite materials can be fabricated.

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Liposomes are routinely coated with a hydrophilic polymer, such as PEG or poly ethylene oxide, to improve the circulation time in vivo

The combination of liposomes and dendrimers has resulted in higher drug loading , as compared with pure liposomes

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TARGETING STRATEGIES

Passive targeting

Tumor vessels are highly disorganized and dilated with a high number of pores, resulting in enlarged gap junctions between endothelial cells .

Migration of macromolecules up to 400 nm in diameter into the surrounding tumor region.

Page 13: Nano-particles and targeting strategies in drug delivery

One of the earliest nanoscale technologies for passive targeting of drugs was based on the use of liposomes.

Liposomes are coated with a synthetic polymer that protects the agents from immune destruction

The microenvironment surrounding tumor tissue, is different from that of healthy cells which supports passive targeting

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• Based on the high metabolic rate of fast-growing tumor cells, they require more oxygen and nutrients. Consequently, glycolysis is stimulated to obtain extra energy, resulting in an acidic environment.

• Taking advantage of this, pH-sensitive liposomes have been designed to be stable at physiological pH 7.4, but degraded to release drug molecules at the acidic pH.

• Disadvantage:The passive strategy is further limited because certain tumors do not exhibit an EPR effect, and the permeability of vessels may not be the same throughout a single tumor.

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Active targeting

One way to overcome the limitations of passive targeting is to attach affinity ligands  that only bind to specific receptors on the cell surface to the surface of the nanocarriers by a variety of conjugation chemistries.

Nanocarriers will recognize and bind to target cells through ligand–receptor interactions

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CONCLUSIONS

 Advances in this area have allowed some nanomedicines in the market to achieve desirable pharmacokinetic properties, reduce toxicity etc

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