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Solid Lipid Nanoparticles: A Review

Vishal J. Lingayat*, Nilesh S. Zarekar, Rajan S. Shendge

Department of Pharmaceutics (PG), Sanjivani College of Pharmaceutical Education and Research, Kopargaon

Abstract: Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, clinical medicine, and research, as well as in other varied sciences. This review presents a broad treatment of solid lipid nanoparticles discussing their aims, production procedures, advantages, limitations and their possible remedies. This review presents a broad treatment of solid lipid nanoparticles discussing preparation method, characterization, route of administration of SLNs, generally carried out. Aspects of SLN route of administration and the invivo fate of the carriers are also discussed.

Keywords: solid lipid nanoparticles, methods of preparation, evaluation, route of administration

Citation: Vishal J. Lingayat, Nilesh S. Zarekar, Rajan S. Shendge, Solid Lipid Nanoparticles: A Review. Nanoscience and Nanotechnology Research, 4 (2). 67-72. January 2017. doi:10.12691/nnr-4-2-5

1. Introduction

Solid lipid nanoparticles (SLNs) are introduced as a carrier system for in effectively water dissolvable medication and corrective dynamic medication. Colloidal particles ranging in size between 10 and 1000 nm are known as nanoparticles. They are incorporated from manufactured characteristic polymers and suited to advance medication conveyance and lessen lethality [1]. They have developed as a variable substitute to liposomes as medication carrier. They are fabricated from manufactured/characteristic polymers and preferably suited to improve sedate conveyance and diminish lethality [2]. SLN offer interesting properties, for example, little size, huge surface zone, high medication stacking and the communication of stages at the interface and are appealing for their potential to enhance execution of pharmaceuticals [3]. Solide lipid nanoparticles (SLN) are aqueous colloidal dispersions, the matrix of which comprises of Solide biodegradable lipids. SLNs consolidate the favorable circumstances and maintain a strategic distance from the down sides of a few colloidal carriers of its class, for example, physical stability, assurance of fused labile medications from protection, of incorporated labile drugs from degradation, controlled release, excellent tolerability SLN formulations for various application routes (parenteral, oral, dermal, visual, pulmonar, rectal) have been developed and thoroughly characterized in-vitro and in-vivo[4].

Solid lipid nanoparticles are one of the novel potential colloidal transporter system as option materials to polymers which is in distinguishable to oil in water emulsion for parenteral nourishment, however the fluid lipid of the emulsion has been supplanted by a Solide lipid nanopartical on Figure 1.

Figure 1. Structure of Solid Lipid Nanoparticle (Sln) [5]

They have many focal points, for example, great biocompatibility, low danger and lipophilic medications are better conveyed by Solide lipid nanoparticles and the framework is physically stable.

1.1. Advantages of SLN [3,6,7]

• Small estimate and generally contract measure dissemination which gives natural chances to site-particular medication conveyance by SLNs [8].

• Conventional emulsion producing techniques pertinent

• Can be stop dried to shape powdered detailing

• Controlled arrival of dynamic medication over a long stretch can be achieved [8].

• Excellent biocompatibility [9].

• Improve stability of pharmaceuticals [10].

• Excellent reproducibility with a savvy high-weight homogenization technique as the readiness methodology.

• High and enhanced drug content.

• The achievability of consolidating both hydrophilic and hydrophobicmedications.

• The transporter lipids are biodegradable and consequently protected. Avoidance of natural solvents. Enhanced bioavailability of inadequately water dissolvable atoms [11].

• Avoidance of natural solvents underway strategies [12].

• Feasible huge scale generation and cleansing.

1.2. Disadvantages of SLN [3,11,13].

• Poor sedate stacking limit.

• Drug ejection after polymeric move amid capacity.

• Unpredictable gelation propensity.

• The low ability to stack hydrophilic medications because of apportioning impacts amid the generation procedure [14].

2. Aims of SLN’s [15-21].

• Possibility of controlled medication discharge and medication focusing on

• More moderate (less costly than polymeric/surfactant based transporters).

• Incorporation of lipophilic and hydrophilic medications attainable

• Avoidance of natural solvents.

• Problems concerning substantial scale generation and sanitization

• Increased sedate security.

• No biotoxicity of the transporter in light of the fact that, most lipids are biodegradable

• Increased Bioavailability of ensnared bioactive mixes

3. Methods of Preparation of Solid Lipid Nanoparticles [2,7,11,21,22,23,24]

Strategy for readiness of SLN incorporates high shear homogenization, ultrasonication, microemulsion based SLN planning, supercritical liquid innovation, splash drying, dissolvable emulsification/vanishing, dissolvable infusion method and dissolvable emulsification-dissemination [25].

As of late, this method has likewise utilized to plan lipid nanoparticles [26]. This procedure depends on the precipitation of lipid broke down in arrangement. In this strategy dissolvable removal happens and lipid accelerate in a similar time. Dissolvable expulsion is fundamental and can be performed by refining or other technique if don't evacuate under given condition. The lipid nanoparticles arrangement happens after vanishing of the water immiscible natural dissolvable. Partical size is relies on upon the different parameters, for example, add up to be infused, grouping of lipid, temperature, mixing, sort of natural dissolvable and emulsifier [27]. SLNs are set up from lipid, emulsifier and water/dissolvable by utilizing diverse techniques and are enroll beneath.

3.1. High weight homogenization [28,29]

3.1.1. Hot homogenization.

3.1.2. Cold homogenization.

3.2. Ultrasonication/fast Homogenization

3.2.1. Test Ultrasonication.

3.1.2.. Shower Ultrasonication.

3.3. Solvent evaporation method.

3.4. Solvent emulsification-diffusion method.

3.5. Supercritical fluid method.

3.6. Microemulsion based method.

3.7. Spray drying method.

3.8. Double emulsion method.

3.9. Precipitation technique.

3.10. Film-ultrasound dispersion.

4. Characterization of Solid Lipid Nanoparticles (SLNs)

Characterization of Solide lipid nanoparticles is a genuine test because of the little size of the particles andcomplexity of the framework. The essential parameters which should be assessed for the SLNs are, Partical estimate, measure conveyance energy (zeta potential), level of crystallinity and lipid alteration (polymorphism), conjunction of extra colloidal structures (micelles, liposome, super cooled, softens, sedate nanoparticles), time size of circulation procedures, tranquilize , in vitro medicate discharge and surface morphology [30].Several parameters which must be considered in Characterization are as per the following

4.1. Partical Size and Zeta Potential

Size of nanoparticles can be dictated by a few techniques, for example, photon-connection spectrometry (PCS), transmission electron microscopy (TEM), and checking electron microscopy (SEM), SEM joined with vitality dispersive X-Beam spectrometry, filtered test microscopy and fraunhofer diffraction. Among these, the most broadly utilized procedures are PCS and electron microscopy techniques. SEM and TEM are exceptionally helpful fit as a fiddle and morphology of lipid nanoparticles and furthermore permit assurance of Partical size and dissemination. Another progressed tiny strategy utilized for Characterization of nanoparticles is nuclear drive microscopy (AFM) [31]. This is another instrument to picture the first unaltered shape and surface properties of the particles. In this system, the drive acting between the surface and examining tip brings about a spatial determination up to 0.01μm. Laser diffraction procedure could likewise be utilized which is appropriate for sub micrometer run particles and figurings depend on the refractive list of the scattering medium water (1.33) and on the lipid particles [32]. The Partical estimate relies on upon the lattice constituents and also on the sort and measure of emulsifying specialists and lipids. It has been accounted for that expansion in measure of emulsifier declines the mean width of the mass [31]. The size and structure of joined medication additionally influences normal distance across of the SLNs [33]. Photon connection spectroscopy (PCS) is otherwise called dynamic light diffusing. This strategy measures the variance of the power of the scattered light which is created by Partical development and gives a size range from 3 nanometres to 3 microns [34,35].

4.2. Determination of Incorporated Drugs

The measure of medication fused is resolved after partition of the free medication and Solide lipids from the fluid medium and the detachment completed by ultracentrifugation, centrifugation filtration or gel penetration chromatography. Tranquilize substance can likewise be resolved specifically by removing the medication with appropriate dissolvable under ideal conditions and afterward investigation of came about item in SLNs.

Models have been proposed to portray the limitation of medication atoms in SLNs [36]. The improved shell model is described by medication specifically situating at the interface, either by quick hardening of the network lipid or by effective rivalry of the medication for the interface. Sedate scattered by such a model may show a fruitful burst impact amid medication discharge. The homogeneous framework model is portrayed by medication scattered equitably all through the lattice, much like a Solide arrangement. The advanced center model is described by medication selectivity situated at the center of the Solide lipid nanoparticles, maybe because of more quick hardening of the medication in respect to the grid material. The advanced center model would be helpful to create a film controlled discharge design. In spite of the fact that the compound solidness and the discharge energy of medications are to a great extent identified with restriction of medications inside the totals, more research is still required to approve these models.

4.3. In-vitro Drug Release Studies

In-vitro tranquilize discharge studies are for the most part helpful for quality control and also for the expectation of in-vivo energy. Discharge profile of medication can be led in dialysis tubing or without tubing. In dialysis, the SLNs scattering is brought into prewashed dialysis tubing, which is then hermetically fixed and after that dialyzed against disintegration medium at consistent temperature with steady mixing. Tests were taken at various circumstances, centrifuged and measured for medication . Impose and Benita (1990) have revealed another system which keeps away from the fenced in area of the colloidal medication bearer in a dialysis sac and depends on switch dialysis. This technique is not sufficiently touchy to describe fast discharge rate of medication from colloidal transporter [37].

4.4. Storage Stability

The physical solidness of the SLNs amid delayed stockpiling can be controlled by checking changes in Partical estimate, tranquilize substance, appearance and Viscosity. This should likewise be possible by thin layer chromatography [38,39].

Outer parameters, for example, temperature and light give off an impression of being of essential significance for long - term steadiness. The zeta potential ought to be as a rule, stay higher than - 60mV for a scattering to remain physically steady.

4°C - Most positive stockpiling temperature.

20°C- Long term storage did not bring about medication stacked SLN total or loss of medication.

50°C - A fast development of Partical size was watched [40].

4.5. Crystallization Tendency and Polymorphic Behaviour of SLNs

Uncommon thought must be given to crystallization of lipids since this is related with medication fuse and discharge rates. The Solide condition of the particles is of real significance, as it diminishes the portability of joined medications and in this manner keeping drug spillage from the bearer. Fundamental procedures to set up the physic-substance condition of particles incorporate warm investigation and X-beam diffraction [41,42]. In warm investigation most generally utilized strategies are differential warm examination (DTA) and differential filtering Calorimetry (DSC).

5. Evaluation of Solid Lipid Nanoparticles [25,43]

5.1. Electron Microscopy of Solid Lipid Nanoparticles

Solide lipid nanoparticles were seen by transmission electron microscopy. Tests of SLN were weakened to ten time and after that mounted on gold plate. The mounted plates were dried and inspected under a transmission electron magnifying instrument without utilizing any sort of stain. The CCD camera and delicate picture framework was utilized with the transmission electron magnifying instrument to envision SLN [44].

5.2. Zeta potential of Solide Lipid Nanoparticles

Zeta potential of SLN definitions were dictated by Zetasizer). Tests were fittingly weakened with deionized water to get 50 and 200 Kcps for the estimations. Tests were put in the cubit accessible for instrument and zeta potential measured specifically [45,46].

5.3. Particle Size and Polydispersity Index of Solid Lipid Nanoparticles

The normal Partical size and polydispersity file of SLN details were measured by Zetasizer DTS (Malvern Instrument, UK). The specimens of SLN scatterings were weakened with deionized water [45]. The aftereffects of normal Partical size and polydispersity record were gotten from instrumental based computation system [29].

5.4. Encapsulation Efficiency of Solid Lipid Nanoparticles

Measure of testosterone epitomized in Solide lipid nanoparticles were figured as typified productivity (EE). Solide lipid nanoparticles were kept in dialysis tube and dialyzed. Thirty milliliter of 30% v/v PEG 400 in phosphate cushion (pH-6) arrangement was utilized as dialyzing medium [47]. Dialysis of Solide lipid nanoparticles was performed for two hour. The one hundred miligram of dialyzed Solide lipid nanoparticles were taken from dialysis pack and broke down for medication content by elite fluid chromatography (HPLC), (Shimadzu, Japan) at 254 nm. The examples were appropriately weakened and separated through Millipore film channel (0.2 μm).

5.5. Viscosity of Solide Lipid Nanoparticles

Viscosity of testosterone containing Solide lipid nanoparticles was measured by Brookfield viscometer (DV-E viscometer, Brookfield, USA) utilizing shaft no 63 at 30 r/m in surrounding condition. The shaft speed no 63 was settled in viscometer nobe and most extreme torque was measured before watching Viscosity. Viscosity of testosterone containing Solide lipid nanoparticles was measured specifically from the viscometer computerized show [48].

5.6. In Vitro Release Study of Solid Lipid Nanoparticles

The in vitro sedate discharge concentrate Solide lipid nanoparticles was performed by privately created Franz dispersion sort cell. The review was performed at 30±2°C temperature. Receptor compartment of dissemination cell contained 30 ml 30% v/v PEG 400 in phosphate cradle (pH-6) arrangement and was always mixed by an attractive stirrer at 50 r/m. Dialysis layer (sub-atomic weight cut off 12 KD was utilized as discharge hindrance in the middle of receptor and benefactor compartment which was beforehand was with refined water and doused with 30% v/v PEG 400 arrangement. Time to time 5 ml tests was pulled back through the examining port of the dissemination cell in interims one h, more than 8 h. Same measure of 30% v/v PEG 400 arrangement was supplanted instantly. The gathered examples were reasonably weakened and examined by HPLC at 254 nm [49].

6. Route of Administration

SLNs are given by taking after course of organization

6.1. Oral Organization

Oral organization of SLN is conceivable as watery scattering or on the other hand after change into a conventional measurement shape, i.e. tablets, pellets, containers or powders in sachets [50]. For the generation of tablets the fluid SLN scattering can be utilized rather than a granulation Fuid in the granulation process [51]. Types of SLNs planning which are given by oral course are fluid scatterings. SLNs stacked dose shape, for example, tablets, pellets and case. The microclimate of the stomach favors Partical conglomeration because of the causticity and high ionic quality. It is not out of the ordinary that nourishment will largy affect SLN execution [52].

6.2. Parenteral Organization

SLNs for the most part directed intravenously to creatures. Conveyance of SLN were found to have higher medication fixations in lung, spleen and cerebrum, while the arrangement prompted to more dissemination into liver and kidneys [53]. SLN demonstrated higher blood levels in contrast with a business sedate arrangement after intravenous. For parenteral organization, SLN scatterings must be sterile. The mean particle so sterile filtration is un realistic in these cases. [50]

6.3. Transdermal Application

The littlest Partical sizes are watched for SLN scatterings with low lipid content (up to 5%). Drawbacks of dermal organization are low grouping of the scattered lipid and the low thickness. The joining of the SLN scattering in a treatment or gel is important so as to accomplish a plan which can be regulated to the skin [54].

6.4. Pulmonary Administration

An extremely fascinating application has all the earmarks of being the aspiratory organization of SLN. SLN powders can't be regulated to the lung in light of the fact that the Partical size is too little and they will be breathed out. An exceptionally straightforward approach is the aerosolization of fluid SLN scatterings [21]. The critical point is that the SLN ought not total amid the aerosolization. The vaporized beads were gathered by impact of airborne with a glass mass of a measuring glass. This essentially exhibits SLN are appropriate for lung conveyance. After restriction into the bronchial tube and in the alveoli, the medication can be discharged controlledly from the lipid particles [55].

6.5. Rectal Organization

Customary rectal conveyance of medications is as often as possible utilized for pediatric patients because of simple application. At the point when expedient pharmacological impact is required, in a few conditions, parenteral or rectal organization is favored. The plasma levels and helpful adequacy of rectally directed medications were accounted for to be unrivaled contrasted and those given orally or intramuscularly in the comparable measurement [56]. A few reports are accessible on the rectal medication organization through SLN in the writing [57]. Concentrated the fuse of diazepam into SLN for rectal organization so as to give a fast activity. They concentrated that lipid network which is Solide at body temperature is not a gainful framework for diazepam rectal conveyance. They resolved to utilize lipids which dissolve around body temperature in their next tests. PEG covering is by all accounts a confident approach on rectal conveyance and thusly, improvement of bioavailability [58].

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