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Solid Lipid
Nanoparticle (SLN)
Dhakane Sumeet
M.Pharm Pharmaceutics
JSPM’S Rajarshi Shahu College of Pharmacy & Research Tathwade ,Pune 33.
Guided By -
Miss. Ashlesha Pandit Mam
1
Outline • General Introduction to Nanoparticle
• Solid Lipid Nanoparticle (SLN)
• Methods of Preparation
• Characterization
• Research Article Overview
2
This are colloidal particle ranging from size between 10 to 1000
nm
● Ideally optimize the delivery and reduces the toxicity.
● can be manufactured by synthetic and natural polymers.
● However safety of polymer plays an important role in Nanoparticles.
● So to overcome this limitation, LIPID put forward as alternative carrier mainly for
lipophilic drugs.
General Introduction to Nanoparticle
3
Solid Lipid Nanoparticles (SLN)
This are colloidal carriers, Submicron sized lipid emulsion in which
the liquid lipid (oil) is substituted by solid lipid.
● Solid lipid nanoparticles possess a solid lipid core matrix that can solubilize
lipophilic molecules.
● The lipid core is stabilized by surfactants (emulsifiers).
● The emulsifier used depends on administration routes .
4
Structure of
SLN -
Types -
5
Composition
● Lipid – E.g. Fatty acids ( Steric Acid, Palmitic acid)
Waxes ( Cetyl palmitate )
Glycerides ( Monoglycerides, Triglycerides)
● Surfactants- E.g. Span, Tween, Polaxomer, PVA
6
Advantages Of
SLN
• Small size, Large Surface area.
• Controlled and Targeted release.
• Avoidance of organic solvents related to
the production method or methods.
• Use of biodegradable physiological
lipids.
• Enhanced drug penetration into the
skin, localization in certain skin layers,
via dermal application.
7
Disadvantages Of
SLN
• Limited drug loading capacity
• Drug expulsion during storage
• Unpredictable gelation tendency
8
Method of Prepration
A) High Pressure Homogenization ( HOT & COLD )
B) Micro emulsion Technique
C) Solvent Emulsification
D) Ultra sonication
E) preparation by using supercritical fluid
9
A) High Pressure
Homogenization ( HOT & COLD )
10
HOT Emulsion
B) Microemulsion
● 2 Phase system composed of an inner and outer phase (o/w)
● Made by stirring optically transparent mixture at 65-78 °C
● Hot micro emulsion is dispersed in cold water (2-38° C) under stirring.
● High-temperature gradients facilitate rapid lipid crystallization and
prevent aggregation so SLN nanoparticle are formed.
● Ratio of Emulsion and cold water is in the range of 1:25 to 1:50
11
C) Solvent Emulsification / Evaporation
● Lipophilic material & Drug dissolved in water-immiscible organic
solvent, which is emulsified in aqueous surfactant phase & Stirred.
● So emulsion is formed which is further subjected to Evaporation
● Nanoparticle dispersion is formed by precipitation of the lipid in the
aqueous medium
12
Lipid Phase
Lipid + Drug
Water + surfactant
Liquid SLN Solid SLN
13
D) Ultra sonication
14
Ultra sonication
● Problem of this method is broader particle size distribution ranging
into micrometer range
● Can cause physical instability like particle growth upon storage.
● metal contamination due to ultrasonication is also a big problem
● high speed stirring and ultrasonication are used combined and
performed at high temperature so above problem can be avoided
15
E) Preparation by using supercritical fluid
16
E) Preparation by using supercritical fluid
● solvent-less processing
● prepared by the rapid expansion of supercritical carbon dioxide
solutions
● Carbon dioxide (99.99%) was the good choice as a solvent for this
method
17
Charecterization
A) Zeta potential –
● It gives information about the magnitude of the electrostatic repulsion
or attraction between particles in the aqueous suspension of SLN.
● Can be analyzed using zeta potential analyzer or zetameter
B) Shape and surface morphology –
● Scanning electron microscopy (surface topography)
● Optical microscopy (observe the small objects)
● Transmission electron microscopy (observe crystal structure)
18
Charecterization
C) Other –
● Density – Pycnometer
● Viscosity - Viscometer
● Crystallinity – X-ray diffraction
19
Applications
1) Parenteral administration-
● SLN when injected intravenously, SLN are sufficiently small to circulate
in the microvascular system. Hence can be used for parenteral
administration.
2) Pulmonary administration-
● SLN powders cannot be administered to the lung because the particle
size is too small and they will be exhaled.
● Simple approach for PA is the aerosolization of aqueous SLN
dispersions.
● The important point is that the SLN should not aggregate during the
aerosolization. 20
3) Topical application -
the SLN can utilized for topical delivery. Due lipophilic nature of SLN
it can easily penetrate through layer of skin and show pharmacological
effect.
4) Ophthalmic administration -
SLN have a prolonged retention time at the eye. lipids of SLN are easy
to metabolize and open a new ways for ophthalmological drug delivery
without impairing vision.
21
Research Article
Title - Solid-lipid nanoparticle formulation improves antiseizure action of
cryptolepine
22
Abstract -
● Study aims to investigate cryptolepine, the major alkaloid of cryptolepis
sanguinolenta as well as its solid-lipidnanoparticle formulation for
potential antiseizure activity.
● Antiseizure activity of SLN formulation of cryptolepine (sln-cryp) was
investigated using pentylenetetrazole (ptz)-induced model of seizure
(zebrafish).
● Permeability of the compound across the blood brain barrier (BBB)
were also assessed.
● This study reveals that the solid-lipid nanoparticle formulation of
cryptolepine improves its BBB permeability.
23
Materials
Benzocaine; Dimethylsulfoxide (DMSO); Pentylenetetrazole (PTZ);
Poloxamer-188 propylene glycol, stearic acid, and Diazepam (Diaz)
Extraction and isolation of cryptolepine-
3 L of Methanol was used to extract 900 g of pulverized dried roots of
Cryptolepis sanguinolenta via Soxhlet at 50 ◦C for a period of 48 h to yield a
dark crude extract.
Identification done by UV and melting point.
24
Preparation of SLN-
● By solvent-evaporation process.
● (A) Surfactant poloxamer-188 (4 mg) was dissolved in water (10 ml).
About 3 ml of propylene glycol (co-solvent) was added to it.
● (B) 50 mg stearic acid was added to the lipid formulation. Cryptolepine
(5 mg) solubilized in 10 ml ethanol and added to the lipid formulation
● stirred the solution for 45 min, 15 min sonication as well as
centrifugation at 11,500 g force at 25 ◦C for a period of 15 min.
● freeze-dried solid nanoparticle were formed
25
Evaluation -
● Release of cryptolepine from SLN-CRYP in vitro
- Done by e dialysis bag method.
- 5 mg/ml cryptolepine solution in methanol, 5 mg/ml cryptolepine
suspension in water and 10 mg/ml SLN-CRYP in water were transferred to the
pre-soaked dialysis bag which was sealed at both ends and then suspended in 200
ml of phosphate buffer (ph 7.4 & 37 ± 0.5 ◦C), stirred constantly at 50 rpm.
- At time points 0, 1, 2, 3, 6, 8, 12 and 24 h, aliquots (2 ml) were taken from the
receiver compartment
- and analyzed by UV
- Obs-Cryptolepine was released from the SLN slower than that from the
solution/suspension
26
Drug release
27
Evaluation -
● permeability assay
- Done by Parallel artificial membrane permeability assay (PAMPA)-BBB
- Permeability of cryptolepine was low for solution and suspension.
(Pe value of 0.32 ± 0.01 × 10− 6 cm/s)
- Permeability was increased in the SLN formulation.
(Pe value of 10.81 ± 0.19 × 10− 6 cm/s.)
28
Conclusion
● Study helped to overcome its cell transportation limitations
with help of solid-lipid nanoparticle formulation of cryptolepine.
● SLN formulation enhances its BBB permeability which
contributes significantly to improved antiseizure activity.
● Drug release assay has shown that the SLN releases
cryptolepine in a controlled manner.
29
References
● S. MUKHERJEE*, S. RAY AND R. S. THAKUR, Solid Lipid Nanoparticles: A Modern Formulation Approach in
Drug Delivery System, Indian J. Pharm. Sci., 2009, 71 (4): 349-358.
● Neda Naseri, Hadi Valizadeh, and Parvin Zakeri-Milani, Solid Lipid Nanoparticles and Nanostructured Lipid
Carriers: Structure, Preparation and Application, Adv Pharm Bull. 2015 Sep; 5(3): 305–313. Published online
2015 Sep 19. doi: 10.15171/apb.2015.043
● G. Swathi, N. L. Prasanthi, S. S. Manikiran and N. Ramarao, SOLID LIPID NANOPARTICLES: COLLOIDAL
CARRIER SYSTEMS FOR DRUG DELIVERY, International Journal of Pharmaceutical Science and Research
(2010), Vol. 1, Issue 12
● Üner M. (2016) Characterization and Imaging of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers.
In: Aliofkhazraei M. (eds) Handbook of Nanoparticles. Springer, Cham. https://doi.org/10.1007/978-3-319-
15338-4_3
30
THANK YOU
31

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Solid Lipid Nanoparticle

  • 1. Solid Lipid Nanoparticle (SLN) Dhakane Sumeet M.Pharm Pharmaceutics JSPM’S Rajarshi Shahu College of Pharmacy & Research Tathwade ,Pune 33. Guided By - Miss. Ashlesha Pandit Mam 1
  • 2. Outline • General Introduction to Nanoparticle • Solid Lipid Nanoparticle (SLN) • Methods of Preparation • Characterization • Research Article Overview 2
  • 3. This are colloidal particle ranging from size between 10 to 1000 nm ● Ideally optimize the delivery and reduces the toxicity. ● can be manufactured by synthetic and natural polymers. ● However safety of polymer plays an important role in Nanoparticles. ● So to overcome this limitation, LIPID put forward as alternative carrier mainly for lipophilic drugs. General Introduction to Nanoparticle 3
  • 4. Solid Lipid Nanoparticles (SLN) This are colloidal carriers, Submicron sized lipid emulsion in which the liquid lipid (oil) is substituted by solid lipid. ● Solid lipid nanoparticles possess a solid lipid core matrix that can solubilize lipophilic molecules. ● The lipid core is stabilized by surfactants (emulsifiers). ● The emulsifier used depends on administration routes . 4
  • 6. Composition ● Lipid – E.g. Fatty acids ( Steric Acid, Palmitic acid) Waxes ( Cetyl palmitate ) Glycerides ( Monoglycerides, Triglycerides) ● Surfactants- E.g. Span, Tween, Polaxomer, PVA 6
  • 7. Advantages Of SLN • Small size, Large Surface area. • Controlled and Targeted release. • Avoidance of organic solvents related to the production method or methods. • Use of biodegradable physiological lipids. • Enhanced drug penetration into the skin, localization in certain skin layers, via dermal application. 7
  • 8. Disadvantages Of SLN • Limited drug loading capacity • Drug expulsion during storage • Unpredictable gelation tendency 8
  • 9. Method of Prepration A) High Pressure Homogenization ( HOT & COLD ) B) Micro emulsion Technique C) Solvent Emulsification D) Ultra sonication E) preparation by using supercritical fluid 9
  • 10. A) High Pressure Homogenization ( HOT & COLD ) 10 HOT Emulsion
  • 11. B) Microemulsion ● 2 Phase system composed of an inner and outer phase (o/w) ● Made by stirring optically transparent mixture at 65-78 °C ● Hot micro emulsion is dispersed in cold water (2-38° C) under stirring. ● High-temperature gradients facilitate rapid lipid crystallization and prevent aggregation so SLN nanoparticle are formed. ● Ratio of Emulsion and cold water is in the range of 1:25 to 1:50 11
  • 12. C) Solvent Emulsification / Evaporation ● Lipophilic material & Drug dissolved in water-immiscible organic solvent, which is emulsified in aqueous surfactant phase & Stirred. ● So emulsion is formed which is further subjected to Evaporation ● Nanoparticle dispersion is formed by precipitation of the lipid in the aqueous medium 12
  • 13. Lipid Phase Lipid + Drug Water + surfactant Liquid SLN Solid SLN 13
  • 15. Ultra sonication ● Problem of this method is broader particle size distribution ranging into micrometer range ● Can cause physical instability like particle growth upon storage. ● metal contamination due to ultrasonication is also a big problem ● high speed stirring and ultrasonication are used combined and performed at high temperature so above problem can be avoided 15
  • 16. E) Preparation by using supercritical fluid 16
  • 17. E) Preparation by using supercritical fluid ● solvent-less processing ● prepared by the rapid expansion of supercritical carbon dioxide solutions ● Carbon dioxide (99.99%) was the good choice as a solvent for this method 17
  • 18. Charecterization A) Zeta potential – ● It gives information about the magnitude of the electrostatic repulsion or attraction between particles in the aqueous suspension of SLN. ● Can be analyzed using zeta potential analyzer or zetameter B) Shape and surface morphology – ● Scanning electron microscopy (surface topography) ● Optical microscopy (observe the small objects) ● Transmission electron microscopy (observe crystal structure) 18
  • 19. Charecterization C) Other – ● Density – Pycnometer ● Viscosity - Viscometer ● Crystallinity – X-ray diffraction 19
  • 20. Applications 1) Parenteral administration- ● SLN when injected intravenously, SLN are sufficiently small to circulate in the microvascular system. Hence can be used for parenteral administration. 2) Pulmonary administration- ● SLN powders cannot be administered to the lung because the particle size is too small and they will be exhaled. ● Simple approach for PA is the aerosolization of aqueous SLN dispersions. ● The important point is that the SLN should not aggregate during the aerosolization. 20
  • 21. 3) Topical application - the SLN can utilized for topical delivery. Due lipophilic nature of SLN it can easily penetrate through layer of skin and show pharmacological effect. 4) Ophthalmic administration - SLN have a prolonged retention time at the eye. lipids of SLN are easy to metabolize and open a new ways for ophthalmological drug delivery without impairing vision. 21
  • 22. Research Article Title - Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine 22
  • 23. Abstract - ● Study aims to investigate cryptolepine, the major alkaloid of cryptolepis sanguinolenta as well as its solid-lipidnanoparticle formulation for potential antiseizure activity. ● Antiseizure activity of SLN formulation of cryptolepine (sln-cryp) was investigated using pentylenetetrazole (ptz)-induced model of seizure (zebrafish). ● Permeability of the compound across the blood brain barrier (BBB) were also assessed. ● This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability. 23
  • 24. Materials Benzocaine; Dimethylsulfoxide (DMSO); Pentylenetetrazole (PTZ); Poloxamer-188 propylene glycol, stearic acid, and Diazepam (Diaz) Extraction and isolation of cryptolepine- 3 L of Methanol was used to extract 900 g of pulverized dried roots of Cryptolepis sanguinolenta via Soxhlet at 50 ◦C for a period of 48 h to yield a dark crude extract. Identification done by UV and melting point. 24
  • 25. Preparation of SLN- ● By solvent-evaporation process. ● (A) Surfactant poloxamer-188 (4 mg) was dissolved in water (10 ml). About 3 ml of propylene glycol (co-solvent) was added to it. ● (B) 50 mg stearic acid was added to the lipid formulation. Cryptolepine (5 mg) solubilized in 10 ml ethanol and added to the lipid formulation ● stirred the solution for 45 min, 15 min sonication as well as centrifugation at 11,500 g force at 25 ◦C for a period of 15 min. ● freeze-dried solid nanoparticle were formed 25
  • 26. Evaluation - ● Release of cryptolepine from SLN-CRYP in vitro - Done by e dialysis bag method. - 5 mg/ml cryptolepine solution in methanol, 5 mg/ml cryptolepine suspension in water and 10 mg/ml SLN-CRYP in water were transferred to the pre-soaked dialysis bag which was sealed at both ends and then suspended in 200 ml of phosphate buffer (ph 7.4 & 37 ± 0.5 ◦C), stirred constantly at 50 rpm. - At time points 0, 1, 2, 3, 6, 8, 12 and 24 h, aliquots (2 ml) were taken from the receiver compartment - and analyzed by UV - Obs-Cryptolepine was released from the SLN slower than that from the solution/suspension 26
  • 28. Evaluation - ● permeability assay - Done by Parallel artificial membrane permeability assay (PAMPA)-BBB - Permeability of cryptolepine was low for solution and suspension. (Pe value of 0.32 ± 0.01 × 10− 6 cm/s) - Permeability was increased in the SLN formulation. (Pe value of 10.81 ± 0.19 × 10− 6 cm/s.) 28
  • 29. Conclusion ● Study helped to overcome its cell transportation limitations with help of solid-lipid nanoparticle formulation of cryptolepine. ● SLN formulation enhances its BBB permeability which contributes significantly to improved antiseizure activity. ● Drug release assay has shown that the SLN releases cryptolepine in a controlled manner. 29
  • 30. References ● S. MUKHERJEE*, S. RAY AND R. S. THAKUR, Solid Lipid Nanoparticles: A Modern Formulation Approach in Drug Delivery System, Indian J. Pharm. Sci., 2009, 71 (4): 349-358. ● Neda Naseri, Hadi Valizadeh, and Parvin Zakeri-Milani, Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Structure, Preparation and Application, Adv Pharm Bull. 2015 Sep; 5(3): 305–313. Published online 2015 Sep 19. doi: 10.15171/apb.2015.043 ● G. Swathi, N. L. Prasanthi, S. S. Manikiran and N. Ramarao, SOLID LIPID NANOPARTICLES: COLLOIDAL CARRIER SYSTEMS FOR DRUG DELIVERY, International Journal of Pharmaceutical Science and Research (2010), Vol. 1, Issue 12 ● Üner M. (2016) Characterization and Imaging of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers. In: Aliofkhazraei M. (eds) Handbook of Nanoparticles. Springer, Cham. https://doi.org/10.1007/978-3-319- 15338-4_3 30