Nanoparticle Drug Delivery System

1. NANOPARTICLES
DRUG DELIVERY
SYSTEM
Name : Vivek Vyas
M.Pharm (Pharmaceutics)
K.B.I.P.E.R

2. INDEX
1. Introduction to Nanoparticles.
2. Type of Nanoparticles.
3. Solid Lipid Nanoparticles(SLNs).
4. Polymeric Nanoparticles(PNPs).
5. Pharmaceuticalaspects of Nanoparticles.
6. References.
2

3. NANOPARTICLES:-
▪ According to the definition from NNI
(National Nanotechnology Initiative),
nanoparticles are structures of sizes ranging
from 1 to 100 nm in at least one dimension.

4. Goals
▪ Decrease drug resistance
▪ Decrease toxicity
▪ Enhance oral bioavailability
▪ Enhance rate of dissolution
▪ Enhance solubility
▪ Increase the stability of drug and formulation
▪ Increase drug targeting ability
▪ Increase patient compliance
▪ Increase surface area
▪ Reduce the dose needed

5.  Type of Nanoparticles:
 Solid Lipid Nanoparticles
 Polymeric Nanoparticles
Ceramic Nanoparticles
Hydrogel Nanoparticles
 Copolymerized Peptide Nanoparticles
 Nanocrystals and Nanosuspensions
 Nanotubes and Nanowires
 Functionalized Nanocarriers

6. SLNs PNPs Nanocrystals
Particle size 10-1000nm 10-1000nm 1000nm
Composition
Solid lipid
+Surfactant +drug
Polymeric
resorvior/ matrix
+ drug
incorporated
Polymeric martix
+ drug
incorporated
Figure
Application
Cancer, Gene
therapy, Brain
targeting
Cancer, DNA
delivery,
Prolonged
delivery
Increase solubility
of drug

7. 1) Solid Lipid Nanoparticles
▪ 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.
▪ Solid lipid nanoparticles are one of the novel potential colloidal carrier
systems as alternative materials to polymers which is identical to oil in
water emulsion for parenteral nutrition, but the liquid lipid of the
emulsion has been replaced by a solid lipid
▪ SLNs are generally composed of solid lipid(s) and surfactant(s).
Different types of lipid can be used such as fatty acids, fatty alcohols,
fatty esters and glycerides.
▪ Surfactants play a significant role in dispersion of melted lipid in the
aqueous phase during formulation and obviously stabilize lipid
nanoparticles during storage

8. •SLN offer unique properties such as small size, large surface
area, high drug loading and the interaction of phases at the
interface and are attractive for their potential to improve
performance of pharmaceuticals.

9. Methods of preparation of solid lipid
nanoparticles
1. High pressure homogenization
1. Hot homogenization
2. Cold homogenization
2. Ultrasonication/high speed homogenization
1. Probe ultrasonication
2. Bath ultrasonication
3. Solvent evaporation method
4. Solvent emulsification-diffusion method

10. 5. Supercritical fluid method
6. Microemulsion based method
7. Spray drying method
8. Double emulsion method
9. Precipitation technique
10. Film-ultrasound dispersion

11. High pressure homogenization A) Hot Homogenization Process

12. B. cold homogenization process
12

13. 2. Ultrasonication/high speed homogenization
SLNs are also prepared by ultrasonication or high speed
homogenization techniques.
For smaller particle size combination of both ultrasonication and
high speed homogenization is required
Advantages
Reduced shear stress.
Disadvantages
Potential metal contamination.
Physical instability like particle growth upon storage.

14. 3. Solvent evaporation
4. Solvent emulsification-diffusion method

15. 5. Microemulsion based method

16. 6. Spray drying method
It's an alternative procedure to lyophilization in order to transform an
aqueous NLC dispersion into a drug product.
It's a cheaper method than lyophilization. But his method can cause
particle aggregation due to high temperature, shear forces and partial
melting of the particle.
7. Double emulsion method
Here the drug is encapsulated with a stabilizer to prevent the
partitioning of drug in to external water phase during solvent evaporation
in the external water phase of w/o/w double emulsion.

17. 8. Precipitation method
The glycerides are dissolved in an organic solvent (e.g.
chloroform) and the solution will be emulsified in an aqueous phase.
After evaporation of the organic solvent the lipid will be precipitated
forming nanoparticles.
9. Film-ultrasound dispersion
lipid + drug add in to organic solutions, after decompression,
rotation and evaporation of the organic solutions, a lipid film is formed.
Then the aqueous solution which includes the emulsions was added,
Using the ultrasound with the probe to diffuser at last, the SLN with the
little and uniform particle size is formed.

18. 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

19. Disadvantages:
 Drug Loading capacity is limited
 High water content
 High pressure induce drug degradation
 Coexistences of several colloidal species
 Lipid crystallization & drug incorporation
- Super cooled melts
- Gelation phenomenon
 Drug expulsion

20. Application of SLNs
▪ Possibility of controlled drug release.
▪ Increased drug stability.
▪ High drug pay load.
▪ No bio-toxicity of the carrier.
▪ Avoidance of organic solvents.
▪ Incorporation of lipophilic and hydrophilic drugs.

21. 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.
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

22. 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.
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

23. 2) Polymeric Nanoparticles
• They are solid colloidal particles ranging in size
from 10 to 1000 nm (1µm).
▪ Drug may be dissolved, entrapped, encapsulated or
attached to a nanoparticle matrix .
▪ Because these systems have very high surface areas,
drugs may also be adsorbed on their surface.
▪ Polymer-based nanoparticles effectively carry
drugs, proteins and DNA to target cells and organs.
▪ Their nanometer-size promotes effective permeation
through cell membranes and stability in the blood
stream.

24. Depending upon
Method of
Preparation
Nanospheres:-
They are the matrix
systems in which
the drug is
physically and
uniformly
dispersed.
Nanocapsules:-
They are the
systems in which
the drug is confined
to a cavity
surrounded by a
unique polymer
membrane.

26. Polymers used in Preparation
Natural
Hydrophilic
Proteins
Polysaccharides
Synthetic
Hydrophobic
Pre-
Polymerized
Polymerized in
process

27. PROTIENS POLYSACHCHARIDES
Gelatin Alginate
Albumin Dextran
Lectin Chitosan
Legumine Agarose
Viciline Pullulan
PRE-POLYMERIZED POLYMERIZED IN PROCESS
Poly E caprolactone Poly Isobutyrl cyano acrylates (PICA)
Poly lactic acid (PLA) Poly butylcynoacryates (PBCA)
Poly lactide co glycolide (PLGA) Polyhexylcyanoacrylates (PHCA)
Polystyrene Poly methyl methacyrlate (PMMA)
Synthetic Hydrophobic Polymers:-
Natural Hydrophilic Polymers:-

28. Nanoparticles preparation using polymer
precipitation methods
1. Solvent extraction I evaporation method :-
This method involves the formation of O/W
emulsion between partially water miscible
solvent containing the polymer and the
drug, and aqueous phase containing the
stabilizer.
2. Salting out method.
3. Solvent displacement method.

30. Nanoparticles preparation using Double Emulsion Solvent
Evaporation Method

32. Nanoparticles preparation using
salting out of polymer

35. Advantages
▪ Increases the stability of any volatile agents & can be
easily and cheaply fabricated in large quantities by a
multimethods.
▪ Has significant advantages over traditional oral and
intravenous methods of administration in terms of
efficiency and effectiveness.
▪ Delivers a higher concentration of pharmaceutical agent.

36. ▪ The choice of polymer and the ability to modify drug
release from polymeric nanoparticles have made them
ideal candidates for cancer therapy, delivery of vaccines,
contraceptives and delivery of targeted antibiotics.
▪ Targeted Drug Delivery System.
▪ Polymeric nanoparticles can be easily incorporated into
other activities related to drug delivery, such as tissue
engineering.

37. Disadvantages
▪ Very costly formulation.
▪ Productivity is more difficult. As a industrial applications,
Technology transfer to commercial production is very difficult.
▪ Reduced ability to adjust the dose
▪ Highly sophisticated technology
▪ Requires skills to manufacture.
▪ Stability of dosage form is big issue owing to its nano size.

38. Therapeutic application of Polymeric
nanoparticles
A. Cancer therapy :
Material -
poly ( alkylcyanoacrylate ) nanoparticles
with anticancer agents, oligonucleotides
Purpose -
Targeting , reduced toxicity, enhanced uptake
of antitumour agents, improved in vitro and in
vivo stability

39. B. Intracellular targeting
• Material :
Poly(alkylcyanoacrylate)polyester nanoparticles
with anti-parasitic or antiviral agents
• Purpose :
Targeting reticuloendothelial system for intracellular
infections

40. C. Prolonged systemic circulation :
• Material :
▪ Polyesters with adsorbed polyethylene glycols or pluronics or
derivatized polyesters
• Purpose :
▪ Prolong systemic drug effect, avoid uptake by the
reticuloendothelial system

41. D. Vaccine adjuvant
• Material :
poly ( methylmethacrylate ) nanoparticles with
vaccines ( oral and intramuscular
immunization )
• Purpose :
enhances immune response, alternate
acceptable adjuvant

42. E. Occular delivery :
• Material :
Poly (alkylcyanoacrylate) nanoparticles with
steroids, anti-inflammatory agents, anti bacterial
agents for glucoma
• Purpose :
improved retention of drug I reduced wash
out.

43. F. DNA delivery :
• Material :
• Purpose :
DNA-gelatin nanoparticles, DNA-chitosan
nanoparticles, PDNA-poly(D, L) lactic acid
nanoparticles
Enhanced delivery and significantly higher
expression levels

45. PHARMACEUTICALASPECTS OF
NANOPARTICLES:
▪ From pharmaceutical point of view nanoparticles prepared
should be free from toxic impurities, should be easy to
store and administer and should be sterile if parenterally
used.
▪ Three parameters performed before releasing them for
clinical trials are:-
1. Purification
2. Freeze drying
3. Sterilization

46. Purification of Nanoparticles
▪ Commonly used methods are:-
1. Gel filtration
2. Dialysis
3. Ultra-centrifugation
4. Cross flow filtration

47. Freeze drying of Nanoparticles
▪ This technique involves the freezing of the nanoparticles
suspension and subsequent sublimation of its water
content under reduced pressure to get free flowing
powder material.
Advantages :
▪ Prevention from degradation.
▪ Prevention from drug leakage, drug desorption .
▪ Easy to handle and store and helps in long term preservation.
▪ Readily dispersed in water without modifications in
▪ their physicochemical properties

48. Sterilization of Nanoparticles
▪ Sterilization of nanoparticles can be achieved by
using:-
1. Aseptic techniques
2. Autoclaving
3. Ƴ radiation

49. References:-
▪ Encyclopedia of controlled drug delivery system edited by
Edith Mathiowitz, Pg. no:551-564.
▪ Vyas S.P. , Khar R.K. Targeted & Controlled Drug Delivery,
Novel Carrier Systems, CBS Publication ,2002 ,Page No.249-
277,331-387.
▪ www.pharmainfo.net/reviews/nanoparticles-and-its-
applications-field-pharmacy
▪ Nanoparticles –A Review by VJ Mohanraj & Chen Y, Tropical
Journal of Pharmaceutical Research 2006; 5(1): 561-573
▪ Google.com(images)

50. ▪ Zhang G, Niu A, Peng S, Jiang M, Tu Y, Li M, Wu C,
“Formation of Novel Polymeric Nanoparticles”, vol. 34, no. 3,
2001 / accounts of chemical research, pg .249-256.
▪ 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.
▪ Ranade VV. Drug delivery systems. 1. site-specific drug
delivery using liposomes as carriers. J Clin Pharmacol. 1989
Aug;29(8):685-94.