3. Polymeric Nanoparticles
ā¢ Nanoparticles are subnanosized colloidal structures composed of
synthetic or semi synthetic polymers
ā¢ The polymeric nanoparticles can carry drugs, proteins, antigens and
DNAto target cells and organs..
ā¢ Drug may be dissolved, entrapped, encapsulated or attached to a
nanoparticle matrix .
ā¢ Because these systems have very high surface areas, drugs may also
be adsorbed on their surface.
ā¢ Their nanometer-size promotes effective permeation through cell
membranes and stability in the blood stream 3
4. ā¢ These bioactives are entrapped in the polymer matrix as particulates
enmesh or solid solution or may be bound to the particle surface by
physical adsorption or chemically.
ā¢ Nanocapsules: They are the systems in which the drug is confined to
a cavity surrounded by a unique polymer membrane.
ā¢ Nanospheres: They are the matrix systems in which the drug is
physically and uniformly dispersed.
4
5. 5
Advantages
ā¢ Increases the stability of any volatile agents & can be easily and cheaply
fabricated in large quantities by a multi-methods.
ā¢ Has significant advantages over traditional oral and intravenous methods of
administration in terms of efficiency and effectiveness.
ā¢ Delivers a higher concentration of pharmaceutical agent.
ā¢ 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.
ā¢ Targeted Drug Delivery System.
ā¢ Polymeric nanoparticles can be easily incorporated into other activities
related to drug delivery, such as tissue engineering.
6. 6
Disadvantages
ā¢ Very costly formulation.
ā¢ Yield is low.
ā¢ Productivity is more difficult.
ā¢ Industrial applications, technology transfer to commercial production
is very difficult.
ā¢ Reduced ability to adjust the dose
ā¢ Highly sophisticated technology
ā¢ Requires skills to manufacture.
ā¢ Stability of dosage form is big issue owing to its nano size.
7. Polymers used in Preparation
Natural Hydrophilic Synthetic Hydrophobic
Proteins
Polysaccharides
Pre-Polymerized
Polymerized in
process
7
9. 9
ā¢ Selection of method for preparing nanoparticles depends on the
physicochemical characteristics of polymer & the drug to be loaded.
ā¢ The preparation tech. determine the inner structure, in vitro release
profile & biological fate of these polymeric delivery system.
ā¢ The different systems include
ā¢ Amatrix type system consisting of an entanglement of oligomer or
polymer units (nanoparticles /nanospheres)
ā¢ Areservoir type of system consisting of an oily core surrounded by
an embryonic polymeric shell (nanocapsules)
ā¢ The drug can be entrapped or adsorbed on surface of these
particulate system.
10. 10
Method are classified as
1. Amphiphilic macromolecule cross-linking
a) Heat cross-linking
b) Chemical cross-linking
2. Polymerization based methods
a) Polymerization of monomers in situ
b) Emulsion polymerization
c) Dispersion polymerization
d) Interfacial condensation polymerization
e) Interfacial complexation
11. 11
3. Polymer precipitation methods
a) Solvent extraction/evaporation
b) Solvent displacement (nanoprecipitation)
c) Salting out
12. Polymers used for preparation of nanoparticles & nanocapsules
Polymer use Technique Candidate drug
Hydrophilic
Albumin, gelatin
Heat denaturation & cross
linking in w/o emulsion
Hydrophilic
Desolvation & cross
linking in aqueous
medium
Hydrophilic & protein
affinity
Alginate,chitosan Cross linking in aq.
medium
Hydrophilic & protein
affinity
Dextran Polymer precipitation in
an organic solvent
Hydrophilic
Hydrophobic
Poly(alkylcyanoacrylates)
Emulsion polymerization
Interfacial/polymerization
Hydrophilic
Hydrophobic
Polyesters
Poly(lactic acid,
poly(lactide-co-glycolide),
poly(Īµ-caprolactone)
Solvent extraction-
evaporation
Solvent displacement
Salting out
Hydrophilic, Hydrophobic
Soluble in polar solvent
Soluble in polar solvent
12
13.
14. Nanoparticles preparation by cross linking of
amphiphilic macromolecules
ā¢ It can be prepared from amphiphilic macromolecules, proteins &
polysaccharides which have affinity for aqueous & lipid solvents.
ā¢ The technique of their preparation involves the aggregation of
amphiphiles followed by further stabilization either by heat
denaturation or chemical cross linking.
ā¢ This process occurs in o/w or w/o dispersed system.
15. ļ¶ Cross linking in w/o emulsion
1. The method involves emulsification of bovine serum albumin
(BSA)/human serum albumin (HSA) or protein aq. solution in oil
using high pressure homogenization or high frequency sonication.
2. The w/o emulsion so formed is poured into preheated oil. The
suspension in preheated oil maintained above 1000C is held stirred
for specific time in order to denature & aggregate the protein
contents of aqueous pool completely & to evaporate water.
3. The particles are finally washed with organic solvent to remove
any oil traces & collected by centrifugation
4. The main factors are emulsification energy & temperature (used
15
for denaturation & aggregation.
16.
17. ļ¶ Emulsion chemical dehydration
1. It is used to produce BSAnanoparticles with a narrow size range.
2. Hydroxypropyl cellulose solution in chloroform was used as
continuous phase of emulsion while a chemical dehydrating agent
i.e., 2,2 di-methyl propane was used to translate internal aq. Phase
to solid particulate suspension.
3. This method avoid coalescence of droplets and produces
nanoparticles (~300 nm).
4. Sonication time required for comminution and to keep internal
phase well dispersed is reduced.
18. ļ¶ Phase separation in aqueous medium (desolvation)
ā¢ The protein or polysaccharide from an aq. phase can be desolvated
by pH change or temp change or by adding counter ions. Cross
linking may be affected simultaneously or next to the desolvation
step.
ā¢ Steps: protein dissolution, protein aggregation & protein
disaggregation.
ā¢ Solvent competing agent, sodium sulphate, is mainly used as a
desolvating agent while alcohol are added as desolvating or
disaggregating agent.
ā¢ Addition can be optimized turbidometrically using Nephelometer.
19.
20. ļ¶ pH induced aggregation
ā¢ Gelatin & Tween 20 were dissolved in aq. phase & pH was adjusted
to optimum value.
ā¢ Solutions were heated to 40ĀŗC followed by quenching at 4ĀŗC for 24h.
ā¢ This leads to formation of colloidal dispersion of aggregated gelatin.
ā¢ The aggregates were finally cross linked using glutaraldehyde.
ā¢ The size of nanospheres were of 200 nm.
ā¢ The ideal pH range is 5.5-6.5
21. ļ¶ Counter ion induced aggregation
ā¢ Separation of protein phase may occur by the presence of counter
ions in the aqueous medium.
ā¢ The aggregation can be propagated by adding counters ions followed
by rigidization step.
ā¢ Example: Chitosan nanospheres can be prepared by adding
tripolyphosphate to the medium.
ā¢ Alginate nanoparticles can be prepared by gelation with calcium
ions.
22.
23. Nanoparticles prepared by polymerization methods
ā¢ Polymers used for nanospheres preparation include poly (methyl
methacrylate), poly(acrylamide), poly(butyl cyanoacrylate).
ā¢ Approaches to prepare nanoparticles using in situ polymerization tech. are:
ļ¼ Methods in which the monomer to be polymerized is emulsified in a non
solvent phase (emulsion polymerization)
ļ¼ Methods in which the monomer is dissolved in a solvent that is non solvent
for the resulting polymer (Dispersion polymerization)
ā¢ In Emulsion polymerization method the monomer is dissolved in an internal
phase and in Dispersion polymerization it is taken in dispersed phase.
ā¢ In both cases after polymerization, polymer tends to be insoluble in internal
phase & results into suspension of nanospheres.
24. Emulsion polymerization
ā¢ It may be conventional or reverse, depending upon nature of
continuous phase,
ā Conventional method=Aq. phase in Continuous
ā Reverse method= Organic is continuous phase
ā¢ The two different mechanism involved are micellar nucleation &
polymerization and homogenous nucleation & polymerization.
25. Micellar nucleation & Polymerization
It involves swollen micelles as site of nucleation & polymerization
Monomer is emulsified in non-solvent phase using surfactant
molecules. The process leads to formation of monomer swollen
micelles and stabilized monomer droplets.
The polymerization reaction proceeds through nucleation and
propagation stage in presence of chemical or physical initiator
26. The energy provided by initiator creates free reactive monomer
which collides with unreactive monomer and initiates
polymerization chain reaction.
As monomer is slightly soluble in surrounding phase, it diffuses from
monomer droplets and reach monomer micelles through continuous
phase. Thus polymerization takes places in MICELLES.
27.
28. Homogenous nucleation & Polymerization
It applies in case where monomer is insufficiently soluble in
continuous outer phase
The nucleation and polymerization stages can directly occur in this
phase, leading to formation of primary chains called oligomers.
In this case both monomer droplet and micelles act as monomer
reservoir
29. When oligomer reaches a certain length, they precipitate and form
primary particles, which are stabilized by surfactant molecules.
Depending upon bulk condition and system suitability, the
nanospheres are formed by additional monomer input into primary
particles or by fusion of primary particles.
34. Dispersion polymerization
Here, monomer instead of being dispersed, is dissolved in theAq.
medium, which act as a precipitant for formed polymer.
In-situ controlled polymerization is done where drug may be added to
monomeric phase or to formed polymer for adsorptive loading.
Polymerization is initiated by adding catalyst & proceeds with
nucleation phase followed by growth phase. (stabilizer or surfactant
not required) (fig 9-9)
35. ā¢ Example: The acrylamide or methyl methacrylate monomer is
dissolved in aqueous phase & polymerized by gamma irradiation
ā¢ By chemical initiation (ammonium or potassium peroxodisulphate)
combined with heating to temp. above 65 0C
ā¢ PMMAnanoparticles can be prepared by gamma irradiation in the
presence of antigenic material
e.g. influenza virion, influenza sub unit antigen, bovine serum
albumin, HIV-1 & HIV-2 antigens
36.
37. Interfacial polymerization
ā¢ In this method, the preformed polymer phase is finally transformed to
an embryonic sheath.
ā¢ The polymer & drug are dissolved in a volatile solvent.
ā¢ The solution is poured into a non solvent for both polymer & core
phase.
ā¢ The polymer phase is separated as a coacervate phase at o/w interface.
The mixture turns milky due to formation of nanocapsules.
ā¢ The solvent is subsequently removed under vacuum.
ā¢ This method is used for proteins, enzymes, antibodies & cells.
ā¢ The size of nanocapsules ranges from 30-300 nm.
38.
39.
40. ā¢ Hydrophobic polymer &/or hydrophobic drug is dissolved in a organic
solvent followed by its dispersion in a continuous aq. Phase in which the
polymer is insoluble. External phase contains stabilizer.
ā¢ Depending upon solvent miscibility tech. may called as solvent extraction
or evaporation method.
The polymer precipitation is done by
ā¢ Increasing the solubility of organic solvent in the external medium by
adding an alcohol (isopropanol).
ā¢ By incorporating water into ultraemulsion (to extract solvent).
ā¢ By evaporation of solvent at room temp. by using vacuum.
ā¢ Using an organic solvent which is completely soluble in the continuous aq.
Phase (i.e., acetone) nanoprecipitation.
41. Solvent extraction method
ā¢ This method involves the preparation of o/w emulsion between
partially water miscible solvent containing polymer & drug, & aq.
Phase containing stabilizer.
ā¢ The subsequent removal of solvent or the addition of water to the
system so as to affect diffusion of solvent to external phase
(emulsification diffusion method)
ā¢ The solvent used for polymer is poorly miscible with dispersion
phase & thus diffuses & evaporates out slowly on continual stirring.
ā¢ Dispersion medium miscible polymer solvent (alcohol & acetone
instantaneously diffuses into the aq. phase & polymer precipitates as
tiny nanospheres. 41
43. Double emulsion solvent evaporation method
ā¢ Emulsion solvent evaporation method is modified and a double
emulsion of w/o/w is used.
ā¢ Following evaporation of organic solvents nanoparticles are formed,
which are recovered by ultracentrifugation, washed repetitively with
buffer and lyophilized.
44.
45. Solvent displacement method
ā¢ It is based on interfacial deposition of a polymer following
displacement of a semi polar solvent miscible with water from a
lipophilic solution
ā¢ The organic solvent diffuses instantaneously to the external aq. Phase
inducing immediate polymer precipitation because of complete
miscibility of both the phases
ā¢ If drug is highly hydrophilic it diffuses out into the external aq. phase
while if drug is hydrophobic it precipitates in aq. medium as
nanocrystals.
47. ā¢ The method involves the incorporation of a saturated aq. solution of
polyvinyl alcohol into an acetone solution of polymer under magnetic
stirring to form an o/w emulsion.
ā¢ In nanoprecipitation tech. polymeric solution is completely miscible with
external aq. medium. But in this method miscibility of both the phases is
prevented by saturation of external aq .phase with PVA.
ā¢ Precipitation of polymer occurs when sufficient amount of water is added
to external phase to allow complete diffusion of acetone from internal
phase to aq. Phase.
ā¢ This method is suitable for drugs & polymers that are soluble in polar
solvents such as acetone & ethanol.
Salting out
48.
49. Solid lipid nanoparticles
The solid lipid nanoparticles(SLNās) are submicron colloidal
carriers which are composed of physiological lipid, dispersed in water
or in an aqueous surfactant solution.
They consist of macromolecular materials in which the active
principle is dissolved, entrapped, and or to which the active principle is
adsorbed or attached.
No potential toxicity problems as organic solvents are not used.
SLNs are spherical in shape & diameter range from 10-1000 nm.
To overcome the disadvantages associated with the liquid state of the
oil droplets, the liquid lipid was replaced by a solid lipid shown in fig,
50. Fig. 1: Structure of solid lipid nanoparticle (SLN)
The reasons for the increasing interest in lipid based system are :
1. Lipids enhance oral bioavailability and reduce plasma profile variability.
2. Better characterization of lipoid excipients.
3.An improved ability to address the key issues of technology transfer and
manufacture scale-up.
51. Advantages of SLN
1. Control and target drug release (Small size & narrow size distribution
provides for site specific drug delivery by SLNs).
2. Excellent biocompatibility.
3. Controlled release of active drug over a long period can be achieved
4. Protection of incorporated drug against chemical degradation
5. SLNs can be lyophilized & spray dried
6. No toxic metabolites are produced
7. Surface modification can be easily done
8. Improve stability of pharmaceuticals.
9.High and enhanced drug content.
10.Easy to scale up and sterilize.
11.Enhanced bioavailability of entrapped bioactive compounds. 51
52. 12. Much easier to manufacture than biopolymeric nanoparticles.
52
13. No special solvent required.
14. Conventional emulsion manufacturing methods applicable.
15. Raw materials essential the same as in emulsions.
16. Can be subjected to commercial sterilization procedures (autoclaving or
gamma irradiation).
Disadvantages of SLN
1. Particle growth.
2. Unpredictable gelation tendency.
3. Unexpected dynamics of polymeric transitions
Aims of solid lipid nanoparticles
1. Possibility of controlled drug release.
2. Increased drug stability.
53. 3. High drug pay load.
4. No bio-toxicity of the carrier.
5. Avoidance of organic solvents.
6. Incorporation of lipophilic and hydrophilic drugs.
Principles of drug release from SLNs
The general principles of drug release from lipid nanoparticles are as
1. Crystallinization behavior of the lipid carrier and high mobility of the
drug lead to fast drug release.
2. Higher surface area due to smaller particle size in nanometer range gives
higher drug release.
3. Slow drug release can be achieved when the drug is homogenously
dispersed in the lipid matrix. It depends on type and drug entrapment
model of SLN. 53
54. Methods of preparation of solid lipid nanoparticles
1. High pressure homogenization
A. Hot homogenization
B. Cold homogenization
2. Ultrasonication
A. Probe ultrasonication
B. Bath ultrasonication
3. Solvent evaporation method
4. Solvent emulsification-diffusion method
5. Microemulsion based method
6. Spray drying method
7. Double emulsion method
8. Precipitation technique
9. Film-ultrasound dispersion
54
55. 1. High pressure homogenization
A. Hot homogenization
Disadvantages:
1) temperature induce drug
degradation
2) partioning effect
3) complexity of the crystallization
55
Fig: Solid lipid nanoparticles preparation by hot homogenization process
56. B. Cold homogenization
56
Disadvantages:
1) Larger particle sizes & broader size
distribution
2) does not avoid thermal exposure but
minimizes it
Fig: Solid lipid nanoparticles preparation by cold homogenization process
57. 2. Ultrasonication/high speed homogenization
ā¢ SLNs are also prepared by ultrasonication or high speed
homogenization techniques.
ā¢ For smaller particle size combination of both ultrasonication and
high speed homogenization is required
ā¢ Advantages
Reduced shear stress.
Equipment used is very common
No temperature induced drug degradation
ā¢ Disadvantages
Potential metal contamination.
Physical instability like particle growth upon storage. 57
58. 58
3. Solvent evaporation
ļ¬ Lipophilic material is dissolved in a water immiscible organic solvent
(e.g.cyclohexane) that is emulsified in an aqueous phase.
ļ¬ Upon evaporation of solvent, a nanoparticle dispersion is formed by
ppt. of lipid in aq. Medium.
ļ¬ Adv.: Avoidance of any thermal stress
ļ¬ Disadv.: use of organic solvents.
61. 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 this 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 into external water phase during solvent evaporation in the external
water phase of w/o/w double emulsion.
61
62. 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.
62
63. 63
Pharmaceutical aspects of nanoparticles
ā¢ The important process parameters performed are Purification,
Freeze drying, Sterilization
ā¢ Purification of nanoparticles:-Toxic impurities includes organic
solvents, residual monomers, polymerization initiators, electrolytes,
stabilizers & large polymer aggregates. Most commonly used
method is gel filtration & ultra filtration
64. 64
ā¢ Freeze drying of nanoparticles
ā¢ It includes freezing of nanoparticle suspension & sublimation of
water to produce free flowing powder.
Advantages:
ā¢ Prevention from degradation & or solubilization of the polymer
ā¢ Prevention from drug leakage, drug desorption, drug degradation
ā¢ Nanocapsules containing oily core may be processed in the presence
of mono or disaccharides (glucose or sucrose)
ā¢ Readily dispersible in water without modifications in their
physicochemical properties
65. 65
ā¢ Sterilization of Nanoparticles
ā¢ Nanoparticles for parenteral use should be sterilized to be pyrogen
free before animal or human use.
ā¢ Sterilization in nanoparticles is achieved by using aseptic tech.
throughout their preparation & processing & formulation & by
sterilizing treatments like autoclaving or Ī³- irradiation
66. 66
Characterization of nanoparticles
Parameter Characterization method
Particle size & size distribution Photon correlation spectroscopy, Laser defractometry,
Transmission electron microscopy, Scanning Electron
Microscopy, Atomic force microscopy, Mercury
porosimetry
Charge determination Laser doppler anemometry, Zeta potentiometer
Surface hydrophobicity Water contact angle measurements, rose bengal binding
X-ray photoelectron spectroscopy
Chemical analysis of surface Static secondary ion mass spectrometry, sorptometer
Carrier-drug interaction Differential scanning calorimetry
Nanoparticle dispersion stability Critical flocculation temp (CFT)
Release profile In vitro release character under physiologic & sink
conditions
Drug stability Bioassay of drug extracted from nanoparticles
Chemical analysis of drug
67. 1. Size & morphology:
ā¢ EM (SEM & TEM) are widely used for determining particle size & its distribution.
ā¢ Freeze fracturing of particles allows for morphological determination of inner structure of
particles.
ā¢ TEM permits differentiation among nanocapsules, nanoparticles & emulsion droplets
ā¢ Atomic force microscopy (AFM) images can be obtained in an aq. medium hence used for
investigation of nanoparticle behavior in biological environment.
2. Specific surface:
ā¢ Is determined with the help of Sorptometer.
ā¢ It can be calculated using formula
ā¢ Where,A=specific surface area,
Ī“= density and
d=diameter 67
68. 3. Surface charge & electrophoretic mobility:
ā¢ The nature & intensity of surface charge determines their interaction with
biological environment as well as with bioactive compounds.
ā¢ It is determined by measuring the particle velocity in an electric field. (Laser
DopplerAnemometry)
ā¢ The surface charge of colloidal particles is measured as electrophoretic mobility
which is determined in phosphate saline buffer & human serum.
4. Surface hydrophobicity:
ā¢ Influences in interaction with biological environment (Protein particles & cell
adhesion).
ā¢ It is determined by two phase partition, contact angle measurements, adsorption of
hydrophobic fluorescent or radiolabelled probes.
ā¢ X-ray photoelectron spectroscopy permits the identification of specific chemical
groups on the surface of nanoparticles.
68
69. 4. Density:
ā¢ The density of nanoparticles is determined with helium or air using a gas
Pycnometer
4. Molecular weight measurement of nanoparticles:
ā¢ Molecular weight of the polymer & its distribution in the matrix can be evaluated by
gel permeation chromatography using a refractive index detector.
4. Nanoparticle recovery & drug incorporation efficiency:
ā¢ Nanoparticle yield can be calculated as
6. Drug incorporation efficiency or drug content:-
7. In vitro release:-In vitro release profile can be determined using standard dialysis,
diffusion cell or modified ultrafiltration technique.
69
70. 70
In-vivo fate & biodistribution of nanoparticles
ā¢ The plasma proteins (opsonins) adsorb on to the surface of colloidal carriers &
render particles recognizable to RES.
ā¢ Phagocytosis of particulates by elements of RES (liver, spleen, bone marrow),
liver ( Kupffer cells) is regulated by opsonins & disopsonins (IgA)
72. 72
Various therapeutic applications of nanoparticles /nanocapsules
Application Material Purpose
Cancer therapy Poly(alkylcyanoacrylate)
nanoparticles with anticancer agents,
oligonucleotides
Targeting, reduced toxicity,
enhanced uptake of antitumour
agents, improved in-vivo & in-
vitro stability
Intracellular
targeting
Poly(alkylcyanoacrylate)
Polyester nanoparticles with anti
parasitic or antiviral agents
Target RES for intracellular
interactions
Prolonged systemic
circulation
Polyesters with adsorbed polyethylene
glycols or pluronics
Prolong systemic drug effect,
avoid uptake by RES
Vaccine adjuvant Poly (methylmetacrylate)
nanoparticles with vaccines
(oral & IM injection)
Enhances immune response
73. Application Material Purpose
Peroral
absorption
Poly(methylmetghacrylate)
nanoparticles with proteins &
therapeutic agents
Enhanced bioavailability & protection
from GI enzymes
Ocular delivery Poly(alkylcyanoacrylate) with
steroids, antiinflammatory agents,
antibacterial agents for glaucoma
Improved retention of drugs/ reduced
wash out
DNA delivery DNA gelatin nanoparticles, DNA
chitosan nanoparticles
Enhanced delivery & higher expression
levels
Oligonucleotide
delivery
Alginate nanoparticles, poly (D,L)
lactic acid nanoparticles
Enhanced delivery of oligonucleotide
Other
applications
Poly(alkylcyanoacrylate)
nanoparticles with peptides
For transdermal application
Crosses blood brain barrier
Improved absorption & permeation
73
74. 74
Nanooparticles with asorbed
enzymes
Enzyme immunoassays,
Nanooparticles with radioactive or
contrast agents
Radioimaging
Copolymerized peptide nanoparticles
of n-butyl cyanoacrylate & activated
peptides
Oral delivery of peptides
75. 75
1. SLN as potential new adjuvant for vaccines.
2. Solid lipid nanoparticles in cancer chemotherapy.
3. Solid lipid nanoparticles for delivering peptides and proteins.
4. Solid lipid nanoparticles for targeted brain drug delivery.
5. Solid lipid nanoparticles for parasitic diseases.
6. Solid lipid nanoparticles for ultrasonic drug and gene delivery.
7. SLN applied to the treatment of malaria.
8. Solid lipid nanoparticles in tuberculosis disease.
9. SLN in cosmetic and dermatological preparations.
10. SLN for potential agriculture applications
Applications of SLN
76. 76
References
1. Khar RK and Vyas SP, āTargeted and controlled drug deliveryā
2. Jain N.K. āAdvances in controlled and novel Drug Deliveryā,
CBS publisher & Distributers, Edition 1st 2001, Pg. 408