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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 preparation A : Amphiphilic Macromolecules Cross Linking 1)Heat crosslinking. 2)chemical crosslinking.
C : Polymer precipitation methods 1) Solvent evaporation method 2) Solvent displacement 3) Salting out
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A : Molecular crosslinking in emulsion Surfactant Aqueous protein
Aqueous phase, Distilled water, stabilizer
Emulsification using highpressure homogenization or high frequency sonication O/W emulsion Dilution with preheated oil (100oC) (Heat cross-linking) Or Addition of crosslinking agent (Chemical cross-linking)
Centrifugation and isolation of nanoparticles
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B : Polymerization Methods Emulsion polymerization : It consists of
a) 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.
Micellar nucleation and polymerization Drug
Monomer
Catalyst
Monomer droplet
monomer supply Catalyst
Monomer bearing nanospheres
(micelle)
Nucleated micelle
Stabilized polymeric
(nanospheres)
micelle
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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
Core dispersed polymer phase (O/W emulsion)
Non solvent which precipitates out polymer from either of phases
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 types 1. Solvent evaporation method 2. Solvent displacement 3. Salting out
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Solvent Evaporation Method
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Solvent Displacement Method
Organic phase, Polarsolvent, Oil+polymer+drug
Organic phase, organic solvent, 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) Thermogravimetry 5. 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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Applications: Application
Purpose
Material
Cancer therapy
Targeting, Reduced toxicity, enhance uptake of antitumor 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.
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
