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NANOPARTICLES

A.Anvesh Kumar M.Pharmacy(Pharmaceutics).

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Contents:

•Introduction•Advantages and Disadvantages•Methods of Preparation•Characterization•Evaluation•Applications

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INTRODUCTION

• Nanoparticles are sub-nanosized colloidal structures composed of

synthetic or semi-synthetic polymers.

• Its size ranges from 1-100nm.

• One can distinguish two types

of nanoparticles

1.Nanospheres

2.Nanocapsule

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•Nanospheres - matrix systems. •Nanocapsules - which are reservoir systems composed of

a polymer membrane surrounding an oily or aqueous core.

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ADVANTAGES :

•Reduction in the frequency of the dosages taken by the patient

•More uniform effect of the drug•Reduction of drug Side Effects•Reduced fluctuation in circulating drug levels•Avoids hepatic first pass metabolism

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DISADVANTAGES :•High cost•Productivity more difficult•Reduced ability to adjust the dose•Highly sophisticated technology•Requires skills to manufacture•Difficult to maintain stability of dosage form.

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Methods of preparationA : Amphiphilic Macromolecules Cross Linking 1)Heat crosslinking.2)chemical crosslinking.

B : Polymerization Methods 1) Emulsion polymerization2) Dispersion polymerization3) Interfacial condensation polymerization4) Interfacial complexation

C : Polymer precipitation methods1) Solvent evaporation method2) Solvent displacement3) Salting out

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Aqueous protein

Aqueous phase,Distilled water,

stabilizer

O/W emulsion

Dilution with preheated oil (100oC)(Heat cross-linking) Or Addition of crosslinking agent(Chemical cross-linking)

Centrifugation and isolation of nanoparticles

Emulsification using high-pressure homogenization or high frequency sonication

Surfactant

A : Molecular crosslinking in emulsion

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B : Polymerization Methods

Emulsion polymerization :It consists ofa) Micellar nucleation and polymerization :

Monomer is insoluble in continuous phase.(O/W phase) Aqueous phase

b)Homogenous nucleation and polymerization : Monomer is soluble in continuous phase.(W/O phase) Organic phase.

Monomer bearing Nucleated micelle Stabilized polymeric micelle nanospheres

Catalyst

Monomer dropletCatalystDrug Monomer

monomer supply

(micelle) (nanospheres)

Micellar nucleation and polymerization

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Homogenous nucleation and polymerization

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Dispersion polymerization:

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Interfacial polymer condensation

Core + Drug Polymer phase

Non solvent which precipitates out polymer from either of phases

Core dispersed polymer phase (O/W emulsion)

Nancapsules 30-300nm

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C : Polymer Precipitation Methods:

The polymer precipitation occurs as a consequence of solvent evaporation which can be brought about by increasing solubility of organic solvent in external medium by adding alcohol (Eg. Isopropanolol)

They are 3 types1. Solvent evaporation method2. Solvent displacement3. Salting out

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Solvent Evaporation Method

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Solvent Displacement Method

Organic phase,organic solvent,

polymer+drug

Organic phase,Polarsolvent,

Oil+polymer+drug

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Salting out of Polymer

stirring

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Evaluation of nanoparticles :

1. Particle size : Photon correlation spectroscopy(PCS) : For smaller particle. Laser diffractrometry : For larger particle. Electron microscopy (EM) : Required coating of conductive

material such as gold & limited to dry sample. Transmission electron microscopy (TEM) : Easier method &

Permits differntiation among nanocapsule & nanoparticle . Atomic force microscope Laser force microscope Scanning electron microscope

High resolution microscope

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2.Density : Helium or air using a gas pycnometer Density gradiant centrifugation 3. Molecular weight : Gel permeation chromatography using refractive index detector. 4. Structure & Crystallinity : X-ray diffraction Thermoanalytical method such as, 1) Differential scanning calorimetry 2) Differential thermal analysis 3) Thermogravimetry5. Surface charge: Surface charge of particle can be determined by measuring

particle velocity in electrical field.

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6. Invitro release : Diffusion cell Recently introduced modified Ultra-filtration tech. Media used : phosphate buffer 7. Nanoparticle yield :

8. Drug entrapment efficiency :

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Recent Advances in Nanoparticles

Solid lipid nanoparticle:• SLN are submicron colloidal carriers (50-1000nm) which are

composed of physiological lipid.

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Dry Powder Aerosol:•L ung cancer treatment can be achieved

by using nanoparticles in dry powder aerosol form .

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Application Purpose Material

Cancer therapy Targeting, Reduced toxicity, enhance uptake of anti-tumor agent

Polyalkylcyanoacrylate with anticancer agent

Intra cellular targeting

Target reticuloendothelial system for intracellular infection

Poly alkyl cyanoarylate

Vaccine adjuvant Prolong systemic drug effect. Enhance immune response

Poly methyl metha acrylate nanoparticles with vaccines

DNA delivery Enhanced bioavailability and significantly higher expression level

DNA gelatin nanoparticles, DNA chitosan nanoparticles

Ocular delivery Improved retention of the drug and reduced washed out.

Poly alkyl cyanoacrylate nanoparticles , anti-inflammatory agent

Applications:

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References:

•Targetted and controlled drug delivery by S.P. VYAS and R.K. KHAR

• Jain N.K. “Advances in controlled and novel Drug Delivery”, CBS publisher & Distributers, Edition 1st 2001, Pg. 408

• Indian Drugs Journal, Edition Nov.2011.• http://en.wikipedia.org/wiki/Nanoparticle• http://www.pharmainfo.net/reviews/nanoparticles-review

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