The document discusses solid lipid nanoparticles (SLNs), which are submicron-sized lipid emulsions that offer advantages like controlled drug release, increased stability, and biocompatibility. It covers their preparation methods, sterilization, characterization, and applications in drug delivery, particularly for cancer therapy and gene vectors. Challenges associated with cancer treatment and the unique benefits of using SLNs for targeted drug delivery are highlighted.

1. Department of Pharmacy (Pharmaceutics)Department of Pharmacy (Pharmaceutics) || Sagar savaleSagar savale
Mr. Sagar Kishor SavaleMr. Sagar Kishor Savale
Department of Pharmaceutics
avengersagar16@gmail.com
2015-016

2. Content:
History
Introduction
Advantage of SLNs over Polymeric nanoparticles
Methods of Preparation
Sterilization of SLNs
Analytical characterization of SLNs
Applications of SLNs
Conclusion
 References
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3. History:
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4. 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
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5. Advantages of SLNs:
Control & target drug release
Increased drug stability
High & enhanced drug content
Feasible for carrying both lipophilic & hydrophilic drug
Excellent biocompatibility
Water based technology
Easy to scale up & sterlize
Avoid RES
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6. 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
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8. NLC the more intelligent system….
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9. Advantages of SLNs over polymeric NPs
Polymeric
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
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10. SLNs preparation:
General ingredients include solid lipid, emulsifier & water
Lipid contains triglycerides, partial glycerides, fatty acids,
steroids, waxes
Combination of emulsifier might prevent particle
agglomeration
Emulsifier include soybean lecithin, egg lecithin,
poloxmer etc.
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11. Method of preparation:
High pressure homogenization
- Hot homogenization
- Cold homogenization
Ultrasonication
Solvent emulsification/evaporation
Micro emulsion
Using Supercritical Fluid
 By Spray drying
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12. 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
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13. 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
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14. Ultrasonication:
Adv. :
1) Equipment used is very common
2) No temperature induced drug degradation
Disadv.:
1) Potential metal contamination
2) Broader particle size distribution
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15. 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.
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16. 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 (2-3o
c) &
stirring.
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17. By using Supercritical fluid
Can be prepared by Rapid Expansion of Supercritical Carbon
dioxide solution methods(RESS)
Adv.: 1) Solvent less processing.
By Spray drying method
 Alternative to lyophilization
Disadv.:
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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18. Sterilization of SLNs
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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19. Characterization of SLNs:
[I] Measurement of particle size
Photon correlation spectroscopy
Transmission electron microscopy
Scanning electron microscopy
Field Flow Fractionation (FFF)
X-ray diffraction
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20. [II] Measurement of Zeta Potential
Allows predictions about the storage stability of colloidal dispersion
Zeta potential under 30 mV are required for full electrostatic
stabilization.
[III] Molecular weight
Gel chromatography
Atomic force microscopy
[IV] Surface element analysis
X-ray photoelectron spectroscopy
Electrophoresis
Laser doppler anaemometry
XRD
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21. [V] DENSITY
Helium compression pychnometry
Contact angle measurement
[VI] Molecular analysis
H-NMR
Infra red analysis
[VI] Measurement of Crystallinity, Lipid modification
DSC & X-ray scattering used to investigate status of lipid
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22. [VII] Coexistence of additional colloidal structure
NMR & ESR used for this purpose
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23. Applications
SLNS/ NLCS aS
CoSmeCeutiCaLS
 applied in the preparation
of sunscreens.
 SLN has UV reflecting
properties.
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24. oRaL SLN iN aNtituBeRCuLaR tHeRaPY
Anti-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.
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25. 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
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26. Challenge #1: Cancer comes from our cells –
domestic terrorist!
Bacteria & viruses = easy to
spot
Cancer = difficult to detect,
difficult to treat
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27. Challenge #2: Cancers are different from
patient to patient
Each tumor is like a salad from a salad bar
They all have a unique combination of ingredients (DNA
errors)
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28. Challenge #3: Cancers continue to change
as they grow
Challenge #3: Cancers continue to change as they grow
If a tumor is detected too late, it has probably already won
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29. Rationale of using SLN for anticancer delivery
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30. Tumor Mass
SLNs attack blood vesicles
which nourish metastatic tumors
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31. 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.
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32. 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
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33. Potential of sln in brain targeting
SLNs 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.
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34. 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
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35. 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.
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