solid lipid nanoparticle

Department of Pharmacy (Pharmaceutics) Department of Pharmacy (Pharmaceutics) | | Sagar savaleSagar savale

Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale

Department of [email protected]

2015-016

mailto:[email protected]

Content:HistoryIntroductionAdvantage of SLNs over Polymeric nanoparticlesMethods of PreparationSterilization of SLNsAnalytical characterization of SLNsApplications of SLNsConclusion References

205/02/23 Sagar Savale

History:


Introduction:

Colloidal particles ranging in size between 10 & 1000 nm are known as nanoparticles.

SLNs are new generation of submicron sized lipid emulsion where the liquid lipid(oil) has been substituted by a solid lipid.

Example: Capture - Dior


Advantages of SLNs:Control & target drug releaseIncreased drug stabilityHigh & enhanced drug contentFeasible for carrying both lipophilic & hydrophilic drugExcellent biocompatibilityWater based technologyEasy to scale up & sterlizeAvoid RES


Disadvantages: Drug Loading capacity is limited High water content High pressure induce drug degradation Coexistences of several colloidal species Lipid crystallization & drug incorporation - supercooled melts - gelation phenomenon Drug expulsion


NLC the more intelligent system….


Advantages of SLNs over polymeric NPsPolymeric Nanoparticles Solid Lipid Nanoparticles

Residual contamination Avoid residual contamination

Possible toxicity problems No toxicity problems

Expensive production & a lack of large scale production method

Cost effective methods are available

Lack of suitable sterilization method

Feasible sterilization method available

Not stable as compared to SLNs SLNs formulation stable for even three years have been developed


SLNs preparation:General ingredients include solid lipid, emulsifier & waterLipid contains triglycerides, partial glycerides, fatty acids,

steroids, waxesCombination of emulsifier might prevent particle

agglomerationEmulsifier include soybean lecithin, egg lecithin,

poloxmer etc.


Method of preparation:High pressure homogenization - Hot homogenization - Cold homogenizationUltrasonicationSolvent emulsification/evaporationMicro emulsionUsing Supercritical Fluid By Spray drying


Hot homogenization 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


Cold homogenization 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


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


Solvent emulsification: 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 ppt of lipid in aq. Medium.

Adv.: Avoidance of any thermal stress

Disadv.: use of organic solvents.


Using Microemulsion: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)Adv.: 1) Solvent less processing.

By Spray drying method Alternative to lyophilizationDisadv.: 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. 1705/02/23 Sagar Savale

Sterilization of SLNsFor 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


Characterization of SLNs:[I] Measurement of particle sizePhoton correlation spectroscopy Transmission electron microscopyScanning electron microscopyField Flow Fractionation (FFF)X-ray diffraction


[II] Measurement of Zeta PotentialAllows predictions about the storage stability of colloidal dispersionZeta potential under 30 mV are required for full electrostatic

stabilization.

[III] Molecular weight Gel chromatographyAtomic force microscopy

[IV] Surface element analysisX-ray photoelectron spectroscopyElectrophoresisLaser doppler anaemometryXRDDSC 2005/02/23 Sagar Savale

[V] DENSITYHelium compression pychnometryContact angle measurement

[VI] Molecular analysisH-NMRInfra red analysis

[VI] Measurement of Crystallinity, Lipid modification

DSC & X-ray scattering used to investigate status of lipid


[VII] Coexistence of additional colloidal structure

NMR & ESR used for this purpose


Applications

SLNs/ NLCs as cosmeceuticals

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

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

DNA, plasmid DNA, & other nucleic acid.


Major challenges where nanotech is needed in cancer therapy

Cancer comes from our cells – domestic terrorist!

Cancers are different from patient to patient

Cancers continue to change as they grow


Challenge #1: Cancer comes from our cells – domestic terrorist!Bacteria & viruses = easy to

spot Cancer = difficult to detect,

difficult to treat


Challenge #2: Cancers are different from patient to patientEach tumor is like a salad from a salad barThey all have a unique combination of ingredients (DNA

errors)


Challenge #3: Cancers continue to change as they growChallenge #3: Cancers continue to change as they grow

If a tumor is detected too late, it has probably already won


Rationale of using SLN for anticancer delivery


Tumor Mass

SLNs attack blood vesicles which nourish metastatic tumors

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WHY SLN FOR ANTICANCER THERAPY ?Improved stability of cytotoxic compounds by SLN

encapsulation

Improved pharmacokinetics and drug biodistribution by SLN

Significant anticancer activity of SLN-encapsulated cytotoxic drug.


Changes in biodistribution of anticancer drugs delivered by SLN

Drug Organs with increased drug concentration delivered by SLN

Idarubicin Blood, brain

Etoposide Blood, brain, tumor, liver, lung, spleen, kidney, bone

Doxorubicin Blood, brain

Camptothecin Blood, brain, liver, lung, spleen, kidney, heart


Potential of SLN in brain targetingSLNs taken up readily by the brain due to their lipidic nature.

high potential to treat brain cancer.

New formulations of neuroactive drugs into SLN are expected to improve their pharmacokinetic profile.


References:Muller R.H., Mader K., Gohla S. “ Solid lipid nanoparticles

(SLN) for controlled drug delivery – a review of the state of art” European journal of Pharmaceutics & Biopharmaceutics, 50 (2000) 161-177

Kaur I.P., Bhandari R., Bhandari S., Kakkar V. “ Potential of Solid lipid nanoparticles in brain targeting” Journal of Controlled release, 127 (2008) 97-109

Wong H.L., Bendayn R., Rauth A.M., Yongqiang L., Xiao Y.W. “ Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles’’ Advanced drug delivery reviews, 59 (2007) 491-504


Mehnert W., Mader K. “ Solid lipid nanoparticles Production, characterization and applications” Advanced drug delivery reviews, 47 (2001) 165-196.

Schwarz C., Mehnert W., Lucks J.S., Muller R.H. “ Solid lipid nanoparticles (SLN) for controlled drug delivery Production, characterization and sterilization” Journal of controlled release 30 (1994) 83-96.

Gasco M.R. “ Lipid nanoparticles: perspectives and challenges” Advanced drug delivery reviews, 59 (2007) 377-378.


solid lipid nanoparticle

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