Introduction of NanoparticlesSolid lipid NanoparticlesAdvantage & disadvantages of SLNsMethods of PreparationSterilization CriteriaCharacterization of SLNsApplications of SLNs References

NANOTECHNOLOGY-

It comprises technological developments on the nanometer scale, usually 0.1 to 100 nm. Nanotechnology, the science of the small.

Nano is Greek for dwarf, and nanoscience deals with the study of molecular and atomic particles.

NANOSUSPENSIONS : They are colloidal dispersions of nanosized drug particle that are produced by suitable method and stabilized by suitable stabilizer .

NANOPARTICLES : They are solid colloidal particles sized from 30-100 nm .

NANOSPHERES : Polymer matrices in

which drug is dissolved or dispersed .

NANOCAPSULES : Consists of polymer wall entrapping an oily core in which the drug is dissolved

NANOPARTICLES : Nanoparticles are particles made of natural

or synthetic polymers ranging in size from 50 to 500 nm. They consist of macromolecular materials in which the active principle ( drug or biologically active material ) is dissolved, entrapped, and or to which the active principle is adsorbed or attached.

MATRIX type

RESERVIOR type

Nanospheres- are solid core spherical particulates, which contain drug embedded within the matrix or adsorbed onto the surface.(Matrix type)Nanocapsules- are vesicular system in which drug is essentially encapsulated within the central core surronded by a polymeric sheath.(Reservoir type

NANOPARTICULATE CARRIERS

NANOSHELLS

DENDRIMERS

QUANTUM DOTS

CARBON NANOTUBES

SOLID LIPID NANOPARTICLES

LIPOSOMES

NIOSOMES

POLYMERIC NANOPARTICLES

The solid lipid nanoparticles(SLN’s) are submicron colloidal carriers which are composed of physiological lipid, dispersed in water or in an aqueous surfactant solution.

They consist of macromolecular materials in which the active principle ( drug or biologically active material ) is dissolved, entrapped, and or to which the active principle is adsorbed or attached.

Nanoparticles are particles made of natural or synthetic polymers ranging in size from 50 to 500 nm.

No potential toxicity problems as organic solvents are not used.

Phospholipids monolayer

Small size & narrow size distribution provides for site specific drug delivery by SLNs

Controlled release of active drug over a long period can be achieved

Protection of incorporated drug against chemical degradation

No toxic metabolites are produced

Sterilization can be done by autoclaving or gamma irradiation

Surface modification can be easily done

Drug Loading capacity is limited

High pressure induce drug degradation

Coexistences of several colloidal species

Lipid crystallization & drug incorporation

- supercooled melts

- gelation phenomenon

Drug expulsion

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High pressure homogenization: Hot homogenization Cold homogenizationUltrasonication /high speed homogenization:Solvent emulsification/evaporationMicro emulsion based SLN preparationsSLN preparation by using supercritical fluidSpray drying method

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Melting of the lipid & dissolving/dispersing of the drug in the lipid

Dispersing of the drug loaded lipid in a hot aqueous surfactant mixture.

Premix using a stirrer to form a coarse preemulsion

High pressure homogenization at a temperature above the lipid M.P. Hot O/W nanoemulsion

Solid Lipid Nanoparticles

Disadvantages: 1) temperature induce drug degradation 2) partioning effect 3) complexity of the crystallization

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Melting of lipid & dissolving/dispersing of the drug in the lipid Solidification of the drug loaded lipid in liquid nitrogen or dry ice Grinding in a powder mill Dispersing the powder in a aqueous surfactant dispersion medium High pressure homogenization at room temperature or below. Solid Lipid Nanoparticles

Disadvantages: 1) Larger particle sizes & broader size distribution 2) does not avoid thermal exposure but minimizes it

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SLN were also developed by high speed stirring or sonication

Adv. : 1) Equipment used is very common 2) No temperature induced drug degradationDisadv.: 1) Potential metal contamination 2) Broader particle size distribution ranging into micrometer range.

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Lipophilic material is dissolved in a water immiscible organic solvent (e.g.cyclohexane) that is emulsified in an aqueous phase.

Upon evaporation of solvent, a nanoparticle dispersion is formed

by precipitation of lipid in aq. Medium. The mean diameter of the obtained particles was 25 nm with

cholesterol acetate as model drug and lecithin/sodium glycocholate blend as emulsifier.

Adv:- Avoidance of any thermal stress. Disadv:- use of organic solvents.

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Preparation by stirring optically transparent mixture at 65-70o c composed of a low melting fatty acid, emulsifier, coemulsifier & water.

This hot microemulsion dispersed in cold water (2-3oc) & stirring.

By using Supercritical fluidCan be prepared by Rapid Expansion of Supercritical Carbon

dioxide solution methods(RESS)Carbon dioxide with 99.99% is good solvent.

Adv:- 1) Solvent less processing.

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Alternative procedure to lyophilization in in order to transform

an aqueous SLN dispersion into a drug product.

Disadvantages:- 1) particle aggregation due to high temp., shear forces & partial

melting of particles. 2) Recommended use of lipid with M.P. >700 c for spray drying.

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For parentral & ocular administration SLNs must be sterile.

For lecithin stabilized SLNs autoclaving is possible & it is not possible for sterically stabilized polymers.

Physical stability during autoclave can not be stated, it depends on composition.

SLN dispersion can also be sterilized by filtration.

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[I] Measurement of particle sizePhoton correlation spectroscopy Transmission electron microscopyScanning electron microscopy

[II] Measurement of Zeta PotentialAllows predictions about the storage stability of colloidal

dispersion

Zeta potential under 30 mV are required for full electrostatic stabilization.

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Gel chromatographyAtomic force microscopy

[IV] Surface element analysisX-ray photoelectron spectroscopyElectrophoresisLaser Doppler anaemometry

[V] DensityHelium compression pychnometryContact angle measurement

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[VI] Molecular analysisH-NMRInfra red analysis

[VI] Measurement of Crystallinity, Lipid modificationDSC andX-ray scattering used to investigate status of lipid

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Solid lipid Nanoparticles possesses a better stability and ease of up grad ability to production scale as compared to liposomes.

SLNs form the basis of colloidal drug delivery systems, which are biodegradable and capable of being stored for at least one year .

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Applied in the preparation of sunscreens. SLN has UV reflecting properties.

ORAL SLN IN ANTITUBERCULAR THERAPYAnti-tubercular drugs such as rifampicin, isoniazide, loaded SLNs able to decrease dosing frequency and increase bioavailability.

SLN AS A GENE VECTOR CARRIER Several recent reports of SLN carrying genetic materials such as DNA,

plasmid DNA, & other nucleic acid have been reported.

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Vyas S.P. and Khar R.K. Targeted And Controlled Drug Delivery System, 1stEdition, 2002, CBS Publication;

249 - 277.

Jain N. K., Controlled and novel Drug Delivery, 1st edition 2001, CBS Publication; 292 - 301.

Mukherjee S., Ray S., Thakur R.S. “ Solid lipid nanoparticles: a modern formulation approach in drug delivery system” Indian journal of Pharmaceutical sciences, 71(2009) 349-358.

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Heurtault B., Saulnier P., Pech B., Proust J.E., Benoit J.P. “ Physico-chemical stability of colloidal lipid particles’’ Biomaterials 24 (2003) 4283-4300

Feng S., Chien S. “ Chemotherapeutic engineering: application and further development of chemical engineering principles for chemotherapy of cancer and other diseases” Chemical engineering science 58 (2003) 4087-4114.

Gasco M.R. “ Lipid nanoparticles: perspectives and challenges”Advanced drug delivery reviews, 59 (2007)

377-378.

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