RITUPARNA DAS

ROLL :99/05/PG-III NO: 130035 3rd SEMESTER

Department of Chemistry University of North Bengal

SOLID LIPID NANO PARTICLES:

Solid lipid nanoparticles (SLN) made from solid lipids are attracting major attention as novel colloidal drug carrier for intravenous applications as they have been proposed as an alternative particulate carrier system. SLN are sub-micron colloidal carriers ranging from 50 to 1000 nm, which are composed of physiological lipid, dispersed in water or in aqueous surfactant solution.

Fig.1:Structure of solid lipid nanoparticle

Fig.2:A diagrammatic representation on SLN over emulsions and liposomes

: Advantages of SLN :
Use of biodegradable physiological lipids which decreases the danger of acute and chronic toxicity and avoidance of organic solvents in production methods . Improved bioavailability of poorly water soluble molecules . Site specific delivery of drugs, enhanced drug penetration into the skin via dermal application . Possibility of scaling up. SLNs have better stability compared to liposomes .

Lyophilization possible

Much easier to manufacture than biopolymeric nanoparticles.

No special solvent required. Raw materials essential the same as in emulsions. Very high long-term stability. Application versatility. Can be subjected to commercial sterilization procedures.

: Disadvantages of SLN :
Poor drug loading capacity. Drug expulsion after polymeric transition during storage .

Relatively high water content of the dispersions .

Particle growth. Unpredictable gelation tendency.

Methods of Preparation:
1.High pressure homogenization i. Hot homogenization ii. Cold homogenization 2.Ultrasonication homogenization
6.Supercritical Fluid technology

7.Microemulsion based method

8.Double emulsion method 9.Precipitation technique 10.Film-ultrasound dispersion

3. Solvent evaporation method

4.Solvent emulsification-diffusion method 5.Spray drying method

: Nanostructured lipid carriers (NLC) :

Nanostructured lipid carriers (NLC) are the second generation SLN composed of solid lipid matrix which are incorporated with liquid lipids. NLC with less organized crystalline structure and therefore provides better loading capacity for drug accommodation. To overcome the stability and drug expulsion problems of SLN, the NLC had emerged.

Fig.3:Electron microscopy picture of NLC

: Aims of solid lipid nanoparticles :

Possibility of controlled drug release. Increased drug stability. No bio-toxicity of the carrier.

: Materials used in SLN :

My system of SLN is Soya lecithin , Tripalmitine and Cetyl palmitate. The surfactant I used is Brij-35, a nonionic surfactant.

Fig6:Structural formula of tripalmitine(C51H98O6) Fig4: Structural formula of soyalecithine(C42H80NO8P)

Fig7: Structural formula of Brij-35(C58H118O24)

Fig5: Structural formula of Cetyl palmitate(C32H64O2)

: Reason for choosing this type of system: There is Structural similarity between the components of my system. Brij-35 is easily biodegradable and non toxic as it is used as my surfactant.

: Applications of SLN :
Solid lipid nanoparticles in Drug delivery:

Fig 13: Drug delivery By nanoparticles

Solid lipid nanoparticles in cancer chemotherapy:

Fig.14:A chemotherapy-filled nanoparticle (lavender) is coated with targeting molecules (blue-purple) that bind to cancer cells. Once the nanoparticle is inside a cell, it releases the drugs (yellow). [Art: Nicolle Rager Fuller]

SLN for Parenteral Application: Cationic SLN has been demonstrated to bind genes directly via electrostatic interactions, and have potential benefits in targeted gene therapy in treatment of cancer.

Targeted delivery of solid lipid nanoparticles for the treatment of lung diseases:

Fig.15: Targeted delivery of solid lipid nanoparticles for the treatment of lung diseases

: Analytical characterization of SLN :

Measurement of particle size and zeta potential: 1.Dynamic light scattering (DLS): DLS also known as PCS records the variation in the intensity of the scattered light on the microsecond time scale.

Fig9: Intensity vs size diagram of Solid Lipid NanoParticles

2.Electron microscopy:

Fig 10:Elecronic microscopic image of Solid Lipid NanoParticles

3.Atomic force microscopy (AFM):

Fig 11:AF M image of Solid lipid nanoparticles

: Plan of Work :
The present work aims at the following: To characterize the solid lipid nano particles.

: Experiment :
: Material :
Lipid soylecithin, tripalmitine and cetyl palmitate

(SLC:TP) 1:1 1:1 1:1 1:1 1:1 1:1

Wt% of CP 5% 10% 15% 20% 25% 30%

SLC(mg) 7.2 6.8 6.4 6.0 5.6 5.3

TP(mg) 7.6 7.2 6.8 6.4 6..0 5.6

CP(mg) 0.5 0.9 1.4 1.9 2.4 2.8

Total(mL) 20 20 20 20 20 20

Table:1.Composition of System

: Result :
Table2: Variation in the hydrodynamic diameter of SLN at different time intervals. 1:1 SLC-TP and 5% CP Time/day 1 2 4 11 24 30 81 87 Size/nm 226.3 140.1 168.4 168.1 169 147.9 141.6 148.7 1:1 SLC-TP and 25% CP Time/day 1 7 14 20 71 77 Size/nm 215.5 196.4 176.5 179.4 146.1 138.2 1:1 SLC-TP and 30% CP Time/day 4 5 12 18 69 75 Size/nm 179.6 181.4 173.8 167.6 159.7 151.3 1:1 SLC-TP and 10% CP Time/day 2 7 13 20 26 77 83 Size/nm 183.6 206.3 218.7 160.6 159 153.9 144.7 1:1 SLC-TP and 15% CP Time/day 1 7 20 27 78 84 Size/nm 199.6 202.7 178.5 174.2 149.8 142.8

1:1 SLC-TP and 20% CP Time/day 2 8 15 21 72 78 Time/day 229.9 190.2 182.1 186.1 173.4 172.8

260

240

CP 5% CP 10% CP 15% CP 20% CP 25% CP 30%

220

size/nm

200

180

160

140 0 20 40 60 80 100

time/day

Graph1:Variation in the hydrodynamic diameter of SLN at different time intervals.

Table3: Variation in the Zeta Potential of SLN with varying concentration of Wt % of CP:

Wt % of CP 5 10

Zeta Potential -5.72 -12.1

15
20 25 30

-4.84
-13.5 -9.08 -16.7
zeta potential
-4 -6 -8

Zeta potential/mv

-10 -12 -14 -16 -18 5 10 15 20 25 30

wt % of CP

Graph2:Variation in the Zeta Potential of SLN at different Wt% of CP

: Conclusion :
From the graph 1 the solution containing 20% wt of CP is quite stable. It take 20 days to reach equllibrating position . Others show much fluctuation .

There is a net decrease of Zeta potential value with increasing concentration of CetylPalmitate(Graph:2) . Results are further evidenced through above Figure

-:FUTURE PROSPECTIVE:However, to draw final conclusion on this aspect, further studies using varios combination of lipids are warranted. This can be considered as the future perspective.

: Acknowledgment :
I wish to express my sincere thanks and gratitude to my teacher Dr. A.K. Panda for his immensely valuable guidance and suggestions to complete this work. My thanks and appreciation also goes to all the faculty members of the Department of Chemistry, University of North Bengal for their help and encouragement. I am also thankful to the research fellows Gourab Karmakar,Prasant Nahak, Manish Sapkota, Biplab , Banita Sinha, Moumita Chakraborty, Pritam Guha and my friends for their constant support and encouragement in every step.during this project work.

:References:
1. Coleman Anthony W., Jebors Said, et al. (2008). "para-Acylcalix[n]arenes: from molecular to macroscopic assemblies." Chem. Commun. 2. DA SILVA ADRIANA L. , SANTOS RAQUEL S. , et al. (2012). "Nanoparticle-based therapy for respiratory diseases." An. Acad. Bras. Cinc 85. 3. EKAMBARAM. P, S. A. A. HASAN, et al. (2012). "SOLID LIPID NANOPARTICLES: A REVIEW." Sci. Revs. Chem. Commun 2(1): 80-102. 4. Gambhire Makarand Suresh , Bhalekar Mangesh Ramesh , et al. "Statistical optimization of dithranolloaded solid lipid nanoparticles using factorial design." Brazilian Journal of Pharmaceutical Sciences 47. 5. Garud Akanksha, Singh Deepti, et al. (2012). "Solid Lipid Nanoparticles (SLN): Method, Characterization and Applications." International Current Pharmaceutical Journal 1(11): 384-393. 6. EH, Korkmaz E, et al. (2012). "Resveratrol-loaded solid lipid nanoparticles versus nanostructured lipid carriers: evaluation of antioxidant potential for dermal applications." Int J Nanomedicine 7. Sahu MK, Soni GC, et al. (2012). "Nanostructured Lipid Carrier: The Second Generation of Solid Lipid Nanoparticle." International Journal for Pharmaceutical Research Scholars (IJPRS) 1(3). 8. Singhal Girish B., Patel Rakesh P., et al. (2011). "SOLID LIPID NANO PARTICLES AND NANO LIPID CARRIERS: AS NOVEL SOLID LIPID BASED DRUG CARRIER." International Reseach Journal Of Pharmacy 2(2): 40-52. 9. Wissinga S.A., Kayserb O. , et al. (2003). "Solid lipid nanoparticles for parenteral drug delivery." Advanced Drug Delivery Reviews: 1257-1272.

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