Solid Lipid Nanoparticles and Nanostructured Lipid Carriers

Introduction:

Solid lipid nanoparticles are particulate colloidal drug delivery systems comprised of

solid lipids and ranging in size between 50 and 1000 nm. Solid lipid nanoparticles is generally
spherical in shape which possess a solid lipid core matrix that
can solubilize lipophilic molecules(e.g., purified triglycerides, fatty acids, steroids, or
waxes).The lipid core is stabilized by surfactants (emulsifiers). Solid lipid nanoparticles
(SLNs) have been extensively investigated for topical application of actives for various skin
diseases. SLNs may be used for both hydrophilic and hydrophobic drugs.

Solid Lipid Nanoparticles:

SLN consist of a core of solid lipid with the bioactives being a part of the lipid matrix
.The particle is stabilized by a surfactant layer, which may consist of a single surfactant, but
typically is composed of a mixture of surfactants. SLN can be manufactured from either
nanoemulsions- or microemulsions-yielding particles with distinctly different properties In
general, the use of crystallized lipids instead of liquid lipids has been shown to increase control
over release and stability of incorporated bioactives. This is because mobility of bioactives can
be controlled by controlling the physical state of the lipid matrix.
Methods to Prepare Solid Lipid Nanoparticles:
1. Melt Homogenization:
 Melt homogenization can be carried out by high-pressure homogenization or
highintensity ultrasonication; however, the possibility of metal contamination due to
probe degradation when using highintensity ultrasound should be considered unless a
coated probe is used.
 The presence of metal fragments could lead to increased oxidative degradation of the
bioactive.
 In melt homogenization, the carrier lipid is first mixed with the bioactive ingredient
using a simple stirrer at a temperature above the melting temperature of the carrier
lipid.
 The mixture is then dispersed in a hot surfactant solution to form a coarse hot
emulsion premix.
 The premix is fed into a high pressure homogenizer equipped with a thermostatted
homogenization chamber to form the fine-disperse nanoemulsion.
 The hot nanoemulsion is then cooled under controlled conditions, e.g., by pumping the
solution through a heat exchanger.
 Typical lipid content of SLN produced by melt homogenization range from 5 to 10%,
although successful production of up SLN suspensions with a lipid content of up to
40% has been reported.
 Typical conditions for melt high pressure homogenization include a minimum of three
to five passes through the homogenizer at homogenization pressures of up to 1,500
bar.
2.Melt microemulsification:
 . SLN can be made from microemulsions by first melting the to be dispersed lipid and
mixing it with hot micellar surfactant solution to form an optically transparent
microemulsion.
 Typically, a number of different surfactants such as lecithin, polysorbate 20, polysorbate
60 and co-emulsifier, such as bile salts and butanol are used to form the hot
microemulsion.
 The hot solution is then diluted into cold water (2–3 °C) under stirring thereby solidifying
the lipid and/or the surfactant in the micelle.
 The dilution process is of critical importance, and dilution factors typically range
between 1:25 and 1:50.

3. Cold Homogenization:
 If the bioactive lipids that are to be delivered in the SLN are temperature-sensitive,
degradation during the manufacturing process using melt homogenization or melt
microemulsification can occur.
 In this case, cold homogenization may be used. In cold homogenization, the lipid is
briefly heated, and the bioactive compound dispersed followed by rapid cooling of the
bulk lipid mixture using liquid nitrogen.
 The bulk lipid mixture is then milled to form lipid microparticles using, for example, a
ball mill.
Advantages of SLN:

 SLNs have many benefits including ease of preparation, low cost, high-scale
production, excellent physical stability, good release profile, chemical versatility,
preparation in the absence of organic solvent, no toxicity of lipid carrier system,
biodegradability of lipids, being cheaper than polymeric carrier, being easier to get
approval and reliability and biodegradability of lipids. 
 They combine the advantages of liposomes, polymeric nanoparticles, and emulsions
while minimizing some of their individual disadvantages.

Disadvantages of SLN :

 Disadvantages of SLNs are: Lipid particle growth, tendency to gelation, dynamics of

polymorphic transitions, and their inherent low incorporation rate due to the crystalline
structure of the solid lipid.

Nanostructured Lipid Carriers

Nanostructured Lipid Carriers:

NLCs are the second generation of lipid nanocarriers and are made up of matrix which
contains solid lipid and liquid lipid. To overcome the disadvantages of SLN, NLCs have been
developed. . NLC particles are stable in their physical and chemical properties. NLC facilitates
loading capacity for drug accommodation and it contains different C-chains in the crystalline
structure. Average size between 10 – 500 nm.
BENEFITS OF NLC’s :

 Biodegradability, greater drug protection is the advantages which were exhibited by the
NLCs
 NLCs were used as the extended release of the drug .
 NLCs were used for the entrapment of hydrophobic drugs and hydrophilic drugs .
 Due to the lesser size of lipid particles, the drug penetration into the mucosa is increased
 NLCs considered as safe.

LIMITATIONS OF NLC’s:

 Cytotoxic effects are observed because of the nature of matrix and concentration
 Some surfactants exhibit irritative and sensitizing actions
 Clinical and preclinical studies lacked in the preparation of NLCs.

TYPES OF NLCS NLCs :

1. Imperfect type

2. Amorphous type

3. Multiple type.

1. Imperfect Type:

The imperfections are formed by blending solid and liquid lipids chemically and increase
drug loading. Liquid phase lipid (oil) is present in the minute amounts in the imperfect type of
NLC. During the crystallization process of production, there will be expulsion of drugs in the
imperfect NLC.

2. Amorphous type : NLCs are obtained by blending special types of solid and liquid lipids
in a controlled manner (e.g., isopropyl myristate). This type of NLC forms solid lipid that
lacks any crystalline structure.
3. Multiple type:

This contains solid lipid encapsulates oil nano compartments. In the oil compartments,
the drug is loaded/loaded. Lipid-lipid precipitation method was used for the preparation. In the
lipid matrix, high concentration of liquid lipids is mixed and the drug expulsion can be avoided
by the multiple types of NLC. Oil reaches its solubility limit and precipitates into nano
compartments during the cooling effect

Food applications of NLC:

 The most important types of bioactive lipids that need to be delivered within foods are
fatty acids, carotenoids, oil-soluble antioxidants (tocopherols and polyphenols),
phytosterols, oil-soluble vitamins (A and D) and other nutraceuticals.
 Lipid-soluble bioactive compounds pose a particularly difficult challenge, especially in
fat-free and low-fat foods, which are in growing demand, and enrichment of aqueous-
based food with these compounds has been greatly restricted.
 Omega-3 fatty acids, the major essential fatty acids, are susceptible to oxidative
deterioration. Moreover, the oxidation products of omega-3 fatty acids have unattractive
effect on sensory acceptance of enriched foodstuffs. Thus, these hydrophobic
compounds require stabilization in an aqueous medium and protection against
deteriorating factors.It has been shown that encapsulation of omega-3 fatty acids
decreased its oxidation (in enriched foods) significantly.
  Oil-soluble vitamins are also susceptible to oxidation and may create drug taste in
fortified foods; for these reasons encapsulation of them is often essential before addition
to foods. The current challenges to application of carotenoids as nutraceutical
compounds are poor water-solubility, high melting point, chemical instability, and low
bioavailability (Qian et al., 2012) and delivery systems should therefore be designed to
fortification of foods with carotenoids, efficiently.
 Flavonoids (e.g. quercetin) are a large group of natural polyphenols; many of these
molecules have low bioavailability (due to poor watersolubility), low chemical stability
and undesirable taste and suitable encapsulation system should therefore be designed to
deliver them into foods.
 NLC are particularly suitable for encapsulating and delivering of lipophilic bioactive
molecules and other lipophilic compounds such as flavors, antimicrobials and drugs into
aqueous-based foods. The possibility of NLC as delivery system has been explored for
many compounds in pharmaceutical area. It has been shown that NLC was able to
encapsulate lipophilic drugs and to improve the stability and the bioavailability of them.
 Like nanoemulsions, NLC are optically transparent or only slightly turbid and are
therefore suitable for fortification of transparent beverages.
 The NLC produced by hot homogenization method may be directly added to pasteurized
transparent, translucent and opaque products such as beer, fruit juice and milk. NLC can
also be added to food systems before pasteurization.

Conclusion:

SLN are an exciting new delivery system with potential for multiple applications in the
food and agricultural industries. They are of particular interest to manufacturers of functional
foods that are looking for novel ways to include lipophilic but chemically sensitive bioactive
compounds. Lipid Nanoparticles also offers a number of advantages interms of manufacturing
and handling procedures.For example, lyophilized or spray dried if carrier lipids with melting
temperatures below 700 C are used to obtain shelf- stable powders.
References:

1. Jochen weiss, et.al., 2008. Solid Lipid Nanoparticles as Delivery systems for
Bioactive food components. Food Biophysics. Vol : 3, Pp: 146-154.
2. Fardin Tamjidi, et.al., 2013. Nanostructured lipid carriers (NLC): A potential
delivery system for bioactive food molecules. Innovative Food Science and
Emerging Technologies .Pp: 29-43.