SOLID LIPID NANOPARTICLES: A PROMISING DRUG DELIVERY SYSTEM

SOLID LIPID NANOPARTICLES: A PROMISING DRUG DELIVERY SYSTEM

Indrayani D. Raut^*1, Rajendra C. Doijad ² and Shrinivas K. Mohite ¹

Rajarambapu College of Pharmacy ¹, Kasegaon, Walwa, Sangli - 415404, Maharashtra, India.

Shri Santkrupa College of Pharmacy ², Ghogaon - 415111, Maharashtra, India.

ABSTRACT: Solid lipid nanoparticle is the forfront of the rapidly developing field of nanotechnology and as an alternative to other traditional colloidal carriers like liposomes, polymeric nanoparticles and emulsions as they have advantages like controlled drug release and targeted drug delivery with increased stability. Objective: Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. Due to their unique size dependant properly, lipid nanoparticles offer to devlop the new therapeutics. Method: The incorporation of drugs into nanocarriers offers a new prototype in drug delivery that could be used for several levels of drug targeting. Hence, solid lipid nanoparticles hold great promise for reaching the goal of controlled and site-specific drug delivery and hence have attracted the wide attention of researchers. Conclusion: The present review article focus on overview about the potential advantages, disadvantages, the excipients and all the different methods involved in their production methodology, Characterization and applications. If properly investigated, SLNs may open new vistas in therapy of complex diseases. Special attention is given to models of drug incorporation in SLN and the release pattern of SLN.

Solid lipid nanoparticle, Targeted drug delivery, Production, Characterization, etc.

INTRODUCTION: The field of Novel Drug Delivery System is emerging at an exponential rate with the deep understanding gained in diversified fields of Biotechnology, Biomedical Engineering and Nanotechnology ¹. Nanotechnology is a newer development technology expected to bring revolutionary changes in the field of life sciences.  Nanotechnology, as defined by the National Nanotechnology Initiative (NNI), is the study and use of structures roughly in the size range of 1 -100 nm.

Nanotechnology is the science of matter and material that deal with the particle size in nanometers. These are small scale colloidal particles that are made of non biodegradable and biodegradable polymers and their diameter is about 200 nm. The important goals for research of nanotechnologies in drug delivery include:

1. Reduction in toxicity while maintaining therapeutic effects,
2. Specific drug targeting and delivery,
3. Biocompatible and more safety, and
4. Development of safe medicines.

Nanoparticles are solid polymeric, submicronic colloidal system range between 5 - 300 nm consisting of macromolecular substances that differ in size 10 nm - 1000 nm. The drug of interest is dissolved, entrapped adsorbed, attached or encapsulated into the nanoparticle matrix ². They are manufactured from synthetic / natural polymers and ideally suited to optimize drug delivery and reduce toxicity.

The advantages of using nano particles for nanoparticles loaded with drugs, because of their small scale size can penetrate through small capillaries and are taken up by cells and allow the drug release at appropriate rate and dose at specific sites in the body for a certain time to release the accurate delivery, which enhances the therapeutic response and reduces the toxicity and side effects. The use of biodegradable material for nanoparticles preparation allows sustained release at the target site over a period of days or even weeks. In the middle of the 1990s, different research Groups have focused on different nanoparticles made from solid lipids, called as solid lipid nanoparticles (SLN or lipospheres or nanospheres) Solid lipoid nanoparticles are one of the novel potential colloidal carriers ³ systems in the range of 100 - 150 nm 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 ⁴.

Advantages: SLNs combine the advantages and avoid the disadvantages of other colloidal carriers.

a. SLNs particularly ranging between 120 nm and 200 nm are not taken up readily by the cells present in the RES (Reticulo Endothelial System), thereby bypassing liver and spleen filtration ⁴.

b. It is possible for controlled drug release and site specific drug targeting. Increased scope of drug targeting can be achieved by coating with or attaching ligands to SLNs

c. It is suitable for lipophillic as well as hydrophilic compounds ⁵.

d. Organic solvents are avoided ⁶.

e. It is less toxic than some polymeric nanoparticles because used lipids are physiological and biocompatible ^{2, 7}.

f.It is flexible in sterilization ⁸.

g. Low cost for solid lipid as compared to biodegradable polymers and phospholipids.

h. Ease of manufacture and scale up. It is easy to manufacture than bipolymeric nanoparticles.

i. Better control over release kinetics of encapsulated compound.

j. The SLNs have enhanced stability as compared to the other colloidal carrier systems.

k. Solid lipid nanoparticle as colloidal drug delivery is suitable for different routes of administration like oral, pulmonary, rectal, ophthalmic, dermal and parenterals administra-tion, etc.

l. Protection of drugs sensitive and liable for photochemical, chemical or oxidative degrada-tion.

m. Excellent reproducibility with use of different methods as the preparation procedure ⁹.

n. SLNs can enhance the bioavailability of entrapped bioactive materials.

Disadvantages of SLN:

a. SLNs have poor drug loading capacity ¹⁰.

b. Polymeric transitions during storage may lead to the drug expulsion from the nanoparticles.

c. The low capacity to load water soluble drugs due to partitioning effects during the production process.

d. They have relatively higher water content. (70-99.9%) ¹¹.

General Ingredients: It includes solid lipid(s), Emulsifier(s), and water. The lipid is used here like triglycerides, partial glycerides, fatty acids, steroids etc. The emulsifiers have been used to stabilize the lipid dispersion. The choice of emulsifier depends on the administration of drug, to the parenteral system; there are limits to choose the emulsifiers ¹².

Production Method of Solid Lipid Nanoparticles:

1. High Pressure Homogenization (HPH): In this method lipids are pushed with 100 - 200 bars high pressure through a narrow gap of few microns ranges. Disruption of particles to submicron ranges occur because of the shear stress and cavitations force (due to sudden changes in pressure). Lipid content in the range 5 - 10% normally. This technique is used for nanoemulsion and PTN. There are 2 basic production methods by high pressure homogenization: Hot homogenization and cold Homogenization. In these both techniques, drug is dispersed or solubilized in the lipids above their melting points ¹³.
2. Hot Homogenization: Lipid components are the first melted by heating above melting point. Therefore it can be regarded as homogenization of an emulsion. Drug is either dispersed or dissolved in molten lipids. Then aqueous surfactant is added at the same temperature. This pre-emulsion of the drug loaded lipid melt and aqueous surfactant phase is obtained with high shearing device such as ultra turrax. High pressure homogenization of pre-emulsion is taken at the temperature higher than the melting point of lipid. While increasing temperature heat accelerated drug degradation occurs. The process is continued till desired particle size. 3 - 5 homogenization cycle are sufficient for requisite particle size. After homogenization the nanoemulsion is formed due to liquid nature of lipid. This on cooling gives rise to solid lipid Nanoparticles. This technique is advantage for suitable for scale up ¹³.
3. Cold homogenization: This method has been developed to overcome the problems that occur in hot homogenization.

a. Drug distribution into aqueous phase during homogenization.

b. Temperature induced drug degradation.

c. Complexity of crystallization step of nanoemulsion leading to several alterations and / or super cooled melts ^{14, 15}.

Hot and cold method steps and shown in Table 1. In comparison to hot homogenization in cold homogenization particle size and polydispersity index are more.

2. Micro-emulsion Technique: Gasco and co-workers were the first to develop solid lipid nanoparticles based on the dilution of micro-emulsions. Micro emulsions are clear, thermo-dynamically stable, isotropic system composed of a lipophilic phase, surfactant and co-surfactant (in most cases) and water. The concept of microemulsion technique for the production of SLN was developed and optimized by Lipids used to prepare SLNs are solids at room temperature and hence the microemulsion is prepared at a temperature above the melting point of the lipid. Both the lipid and the aqueous phase containing the emulsifier are mixed in appropriate ratios and stirred so that it will produce a microemulsion. Fig. 1 and 2 Shows the Micro-emulsion process steps used for SLN production.

Step 1: Preparation of Micro-emulsion:

FIG. 1: STEP 1 MICRO-EMULSION

Step 2: Formation of Solid Lipid Nanoparticle:

FIG. 2: STEP 2 OF MICRO-EMULSION

TABLE 1: STEPS OF COLD AND HOT HOMOGENIZATION TECHNIQUE

3. Solvent Emulsification - Diffusion Technique: Another technique which is proposed for production of solid lipid nanoparticles is solvent emulsification-diffusion method ^{16, 17}. In this technique, the solvent used like e.g. benzyl alcohol, butyl lactate, ethyl acetate, isopropyl acetate, methyl acetate must be partially miscible with water. This technique can be carried out either in aqueous phase or in oil phase ^{13, 18}. Initially, both the solvent and water were mutually saturated in order to establish the initial thermodynamic equilibrium of both liquid ³⁸. When heating is required to solubilize the lipid, saturation step was performed at that temperature. Then the lipid and drug were dissolved in water saturated solvent and this organic phase which is internal phase was emulsified with solvent saturated aqueous solution containing stabilizer i.e. dispersed phase using mechanical stirrer. After the formation of o/w emulsion, water is a dilution medium in typical ratio ranges from 1:5 to 1:10, added to the system in order to allow solvent diffusion into the continuous phase, and forming aggregation of the lipid in the nanoparticles. Avoidance of heat during the preparation is the most important advantage of this technique.
4. Solvent Emulsification or Evaporation: In this method, the production of nanoparticle dispersions by precipitation in o/w emulsions. The lipophilic material and hydrophobic drug is dissolved in water-immiscible organic solvents like e.g. cyclohexane, dichloromethane, toluene, chloroform etc and then that is emulsified in an aqueous phase using high speed homogenizer ^{19, 20}. Upon evaporation of the solvent, nanoparticle dispersion is formed by lipid precipitation in the aqueous medium. Thereafter, the organic solvent was evaporated by mechanical stirring at room temperature and decreased pressure (e.g. rotary evaporator) leaving lipid precipitates. Here, the mean particle size depends on the lipid concentration in organic phase. Very small particle size could be obtained with low lipid content (5%) related to organic solvent.
5. Ultrasonication: Ultrasonication or high speed homogenization is one of the methods for the production of SLNs. The advantage of this method is that the equipment used is easily available at lab scale. However, this method suffers from problems such as extensive size distribution ranging into micrometer range. Potential metal contaminations, physical instability like particle growth upon storage are other drawbacks associated with this technique.
6. Supercritical Fluid (SCF) Technology: More recently, attractive new techniques based on SCF technology have been studied as useful alternatives for drying pharmaceutical protein formulations, and to produce solvent‐free particulate drug carriers ⁵. The main advantages of such techniques include possible sterilizing properties of supercritical CO₂ and mild processing conditions, ability of producing microparticles or nanoparticles in the form of dry powders and feasibility of scaling‐up. Carbon dioxide (CO₂) has been used almost exclusively in SCF processing of pharmaceuticals because of its low toxicity, moderate critical pressure and its relatively low critical temperature, and its low cost.
7. Solvent Injection Technique: In this technique, the solid lipid is dissolved in water miscible solvent. The lipid solvent mixture is injected into stirred aqueous phase with or without surfactant. Finally, the dispersion is filtered to remove excess lipid. Emulsion within the aqueous phase aids to produce lipid droplets at the site of injection and stabilize SLNs until solvent diffusion completes ^{21, 22}.
8. Spray Drying: It is an alternative tool to lyophilization in order to transform an aqueous SLN dispersion into a drug product. This is an economic method than lyophilization and recommends the use of lipid with melting point >70°C. This method causes particle agglomeration due to high temperature, shear forces and partial melting of the particle.
9. Melting Dispersion Technique: In this technique drug and solid lipid were melted in an organic solvent which is termed as oil phase and simultaneously water phase was also heated to same temperature as oil phase. Then the oil phase is added slowly in to a small volume of water phase with stirring at higher rpm for few hrs. Then, it was cooled down to room temperature to produce SLNs. Reproducibility was more than ultrasonication method but lesser than that of solvent emulsification evaporation method ²³.
10. Double Emulsion Technique: In double emulsion technique the drug was dissolved in aqueous solution, and then was emulsified in molten lipid. This primary emulsion was stabilized by adding stabilizer (e.g. poloxamer - 407). Then stabilized primary emulsion was dispersed in aqueous phase containing hydrophilic emulsifier. Then, the double emulsion was stirred and was isolated by filtration.
11. Membrane Contactor Technique: In this technique, the liquid phase was pressed at a temperature above the melting point of the lipid through the membrane pores allowing the formation of small droplets. The advantages of this, the control of the SLN particle size by proper choice of process parameters. The aqueous phase was stirred continuously and circulated tangentially into the membrane module, and sweeps away the droplets being formed at the pore outlets. SLNs were formed by cooling of the preparation at the room temperature. Here both the aqueous and organic phases were placed in the thermostated bath to maintain the required temperature and nitrogen was used to create the pressure for the liquid phase. Vitamin E loaded SLN was prepared using this technique to allow large scale production and their stability is demonstrated.
12. Precipitation Technique: Solid lipid nanoparticles can also be produced by a precipitation method which is characterized by the need for solvents. The glycerides will be dissolved in an organic solvent like chloroform and the solution will be emulsified in an aqueous phase. After evaporation of the organic solvent, the lipid will be precipitated forming nanoparticles.

Characterization of SLN: Characterization of the SLNs is necessary for its quality control. However, characterization of SLN is a challenge due to the colloidal size of the particles and the complexity and dynamic nature of the delivery system.

1. Measurement of Particle Size and Zeta Potential: The physical stability of SLNs depends on their size. Photon correlation spectroscopy (PCS) and laser diffraction (LD) are the most effective techniques for determination of particle size. PCS also known as dynamic light scattering measures the variation in the intensity of the scattered light, which is occurred by particle movement. The particle size determination by photon correlation spectroscopy (PCS) detects size range of 3 nm to 3 μm and by laser diffraction in size range of 100 nm to 180 μm. Although PCS is a good device to characterize nano-particles it is capable for the detection of larger microparticles ²⁴.

Zeta potential analyzer or zetameter is used to measure the zeta potential. Before measurement, SLN dispersions are diluted 50 times with the original dispersion preparation medium for size determination and zeta potential measurement ²⁵. A high value of zeta potential may lead to deaggregation of particles in the absence of other complicating factors such as hydrophilic surface appendages or steric stabilizers. Zeta potential measurements can be useful for predictions about the storage stability of colloidal dispersions.

a. Electron Microscopy: Transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) provide way to directly observe nanoparticles. However, SEM is better for morphological examination. TEM has a small size limit of detection ²⁶.

b. Dynamic Light Scattering (DLS): DLS also known as PCS records the variation in the intensity of the scattered light on the microsecond time scale.

c. Static Light Scattering (SLS) / Fraunhofer Diffraction: SLS is an ensemble method in which the light scattered from a solution of particles is collected and fit into fundamental primary variable.

d. Acoustic Methods: It measures the attenuation of the scattered sound waves as a means of determining size through the fitting of physically relevant equations.

e. Nuclear Magnetic Resonance (NMR): NMR can be used to determine both the size and qualitative nature of nanoparticles.

f. Atomic Force Microscopy (AFM): A probe tip with atomic scale sharpness is rastered across a sample to produce a topological map based on forces at play between the tip and the surface ^{14, 27}.

Measurement of Crystallinity and Lipid Modifications:

X-ray Diffraction (Powder X-ray Diffraction) and Differential Scanning Calorimetry (DSC): The geometric scattering of radiation from crystal planes within a solid allow the presence or absence of the former to be determined thus permitting the degree of crystallinity to be assessed. DSC can be used to determine the nature and the speciation of crystallinity within nanoparticles through the measurement of glass and melting point temperature. Thermodynamic stability, lipid packing density and quantification are a serious challenge due to the increase, while drug incorporation rates decrease in the following order:

Super cooled melt < α-modification < β9-modification < β-modification.

3. Co - existence of Additional Structures: The magnetic resonance techniques, nuclear magnetic resonance (NMR) and electron spin resonance (ESR) are powerful tools to investigate dynamic phenomena and the nano-compartments in the colloidal lipid dispersions. Dilution of the original SLN dispersion with water might cause the removal of the surfactant molecules from the particle surface and induce further changes such as crystallization changes of the lipid modification ²⁸.
4. Entrapment Efficiency: The entrapment efficiency of the drug is determined by measuring the concentration of free drug in the dispersion medium.

Ultracentrifugation was carried out using Centrisart, which consist of filter membrane (molecular weight cutoff 20,000 Da) at the base of the sample recovery chamber. The SLNs along with encapsulated drug remain in the outer chamber and aqueous phase moves into the sample recovery chamber. The amount of the drug present in the aqueous phase is determined by HPLC or UV spectrophotometer.

% Entrapment efficiency = [(Initial drug weight–weight of free drug) / Weight of initial drug] × 100%

5. In-vitro drug release: In-vitro drug release studies are used for quality control studies as well as for the prediction of in-vivo kinetics. In this SLN’s due to very small size of the particles, the release rate observed in-vivo can differ greatly from the release obtained in buffer solution. Hence in-vitro release studies remain useful for quality control as well as for evaluation of influence of process parameters on release rate of active components.
6. Dialysis Tubing: In vitro drug release could be achieved using dialysis tubing. The SLNs dispersions are placed in a prewashed dialysis tubing which can be hermetically sealed ³⁰. The dialysis sac is then dialyzed against a suitable dissolution medium at room temperature; the samples are withdrawn from the medium at suitable intervals, centrifuged and analyzed for drug content using a suitable method (U.V. spectroscopy, HPLC etc). The maintenance of sink condition is essential.
7. Reverse Dialysis: In this technique, a number of Small dialysis sac containing 1 ml of dissolution medium are placed in SLN dispersion. The SLNs are then placed into the dissolution medium. The direct dilution of the SLNs is possible with this method; however the rapid release cannot be quantified using this method ³⁰.
8. Franz Diffusion Cell: The SLNs dispersion is placed in the donor chamber of a Franz diffusion cell fitted with a cellophane membrane. The dispersion is then dialyzed against a suitable dissolution medium at room temperature; the samples are withdrawn from the dissolution medium at suitable intervals and analyzed for drug content using a suitable method (U.V. spectroscopy, HPLC etc). The maintenance of sink condition is essential.

Drug Release from SLN: Depending upon the drug solubility and drug / lipid ratio, method of preparation, the drug is located in the core of the particles, in the shell or molecularly dispersed throughout the matrix. There are mainly three drug incorporation models which describe the incorporation of drug into SLN.

1. Solid Solution or Homogenous matrix model.
2. Drug enriched shell, core shell model.
3. Drug enriched core, core shell model.

a. Solid solution                 

b. Drug enriched Shell        

c.  Drug enriched core

FIG. 3: MODELS OF INCORPORATION OF ACTIVE COMPOUNDS INTO SLN

(a) Homogeneous matrix, (b) Drug enriched shell with lipid core, (c) Drug enriched core with lipid shell

The above three models are the function of formulation, combination of solid lipid, active ingredients, surfactants and sometime co-surfactant and of the production techniques (hot vs. cold homogenization)

30. Solid Solution Model: In this, the drug is molecularly dispersed in the lipid matrix when the particles are produced by cold homogenization technique and no surfactant or no drug solubilizing surfactant is used. In this, drug has strongly pronounced interactions with the lipid ^{11, 30}.
31. Drug Enriched Shell Model: In this model of drug incorporation, a solid lipid core forms when the recrystllization temperature of lipid is reached. On reducing the temperature of this dispersion, drug concentrates in the still liquid outer shell of solid lipid nanoparticles ¹⁶.
32. Drug Enriched Core model: In this model of drug incorporation, cooling the nanoemulsion leads to the super saturation of the drug which is dissolved in the lipid and melt at or close to its saturation solubility and the drug participates prior to the lipid recrystallization and finally needs further cooling to the recrystallization of the lipid surrounding the drug as a membrane.

Applications of SLN’s

1. Ophthalmic Administration: Many investi-gations have been made to use nanoparticles for prolonged release of drugs to the eye. The basic drawback of ophthalmologic formulation is the fast removal from the eye, which implies clearance of the applied drug through the nose. It could be shown for nanoparticles that an increased adhesiveness is available leading to higher drug levels at desired site of action. However, the basic problem was that the nanoparticles are of limited toxicological acceptance. It was shown by Gasco that SLN have a prolonged retention time at the eye. This was confirmed by using radiolabiled formulations and γ-scintigraphy. The lipids of SLN are easy to metabolize and open a new ways for ophthalmological drug delivery without impairing vision ³¹.
2. Pulmonary Administration: SLN powders cannot be administered to the lung because the particle size is too small and they will be exhaled. A very simple approach is the aerosolization of aqueous SLN dispersions. The major point is that the SLN should not aggregate during the aerosolization. The aerosol droplets were collected by collision of aerosol with a glass wall of a beaker. This basically demonstrates that SLN are suitable for lung delivery. After localization into the bronchial tube and in the alveoli, the drug can be released in a controlled way from the lipid particles ³².
3. SLNs as a Targeted Carrier for Solid Tumors: One of the most important challenges in drug delivery is to get the drug at the place it is needed in the body thereby avoiding or reducing the side effects to non diseased organs. The non restricted toxicity of chemotherapeutics thus limits the full use of their therapeutic potential. Local drug delivery or drug targeting results in increased local drug concentrations and provides strategies for more specific therapy. Nanoparticles have specific particles as tools to enable these strategies. SLNs have been reported to be useful as drug carriers to treat neoplasms ³³. Tumour targeting has been achieved with SLNs loaded with drugs like methotrexate ¹³, paclitaxel ³⁴ and camptothecin ³⁵.
4. SLNs as Cosmeceuticals: The SLNs have been applied in the preparation of sunscreens and as an active carrier agent for molecular sunscreens and UV blockers. Cosmeceuticals is rising as the major application target of these carriers. Carrier systems like SLNs and NLC were formulated with a point of view to meet manufacturing needs like scale up, qualification and validation, simple technology, low cost etc ³⁶ The SLNs have been functional in the preparation of sunscreens and as an active carrier agent for molecular sunscreens and UV blockers ³⁷.
5. SLNs for Liver Targeting: Liver-targeting SLNs with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA) was prepared. The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated SLNs and conventional SLNs were successfully prepared by a high - pressure homogenization method.

The encapsulation of Cuc B in SLNs resulted in the improvement of cytotoxic activity and galactosyl ligand could further improve the cellular accumulation and cytotoxicity of Cuc B. The incorporation of N-HLBA into SLNs considerably improved the liver target ability of Cuc B-loaded SLNs and galactosylated SLN had a great potential as a drug delivery carrier for improved liver target ability.

6. SLNs for Potential Agriculture Application: Essential oil extracted from Artemisia arborescens L. when incorporated in SLN, were able to reduce the rapid evaporation compared with emulsions and the systems have been used in agriculture as a suitable carrier of ecologically safe pesticide.
7. Solid Lipid Nanoparticles for Antimicrobial Drug Delivery: Firstly, SLNs contain occlusive excipients that, upon appliance on skin, readily form a thin film to lessen water evaporation and retain skin moisture. SLNs can facilitate the delivery of anti-tuberculosis drugs such as rifampin, Isoniazid and pyrazinamide to the lungs as well as to the lymphatic systems. SLNs can provide a sustained release of the carried antimicrobial payloads, which then can effectively eliminate the infectious microbes harbored at these lymphatic sites. Eventhough the development history of SLN-based antimicrobial drug delivery systems is relatively shorter than other nanoparticle systems such as liposomes and polymeric nanoparticles, SLNs have shown great therapeutic potentials.
8. SLNs in Breast Cancer and Lymph Node Metastases: Mitoxantrone-loaded SLN local injections were formulated to reduce the toxicity and improve the safety and bioavailability of drug. Efficacy of doxorubicin (Dox) has been reported to be enhanced by incorporation in SLNs. In the methodology the Dox was complexed with soybean-oil-based anionic polymer and dispersed together with a lipid in water to form Dox-loaded solid lipid nanoparticles. The system has enhanced its efficacy and reduced breast cancer cells.
9. Oral SLNs in Antitubercular Chemotherapy: Antitubercular drugs such as rifampicin, isoniazide, pyrazinamide-loaded SLN systems were able to reduce the dosing frequency and improve patient compliance. Antitubercular drugs loaded SLNs were prepared using solvent diffusion technique ³⁸.
10. SLNs as Gene Vector Carrier: Cationic solid lipid nanoparticles have established themselves during the past decades. They can well bind DNA directly via ionic interaction and intervene gene transfection. SLN can be used in the gene vector formulation ³⁹.

CONCLUSION: SLNs are relatively novel drug delivery systems, having received primary attention from the early 1990’s and future holds great promise for its systematic investigation and exploitation. SLN as colloidal drug carrier combines the advantage of polymeric nano-particles, liposome; like improved physical stability, feasibility of incorporation of lipophilic and hydrophilic drugs, economic, ease of scale-up, and manufacturing. SLNs can effect site specific and sustained release of drug. SLNs are prepared by various advanced techniques. SLNs have been used extensively for applications in drug discovery, drug delivery, and diagnostics and for many others in medical field.

ACKNOWLEDGEMENT: The authors are thankful to Rajarambapu College of Pharmacy, Kasegaon - 415404, Maharashtra, India for their valuable support and permission to carry out the work.

CONFLICT OF INTEREST: Authors don’t have any conflict of interest with any person or institution.

REFERENCES:

1. Nadkar S and Lokhande C: Current Trends in Novel Drug Delivery- An OTC Perspective. Pharma Times 2010; 42 Suppl 4: 17-23.
2. Muller RH, Maassen S, Schwarz C and Mehnert W: Solid lipid nanopaticles (SLN) as potential carrier for human use: interaction with human granulocytes. J Control Release 1997; 47: 261-69.
3. Cavalli R, Peira E, Caputo O and Gasco MR: Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with β-cyclodextrin. J. Pharm. 1999; 59-69.
4. Jenning V, Lippacher A and Gohla SH: Medium scale production of solid lipid nanoparticles (SLN) by high pressure homogenisation. J Microencap. 2002; 19: 1-10.
5. Hu FQ, Yuan H, Zhang HH and Fang M: Preparation of solid lipid nanoparticles with clobetasol propionate by a novel solvent diffusion method in aqueous system and physicochemical characterization. Int J Pharm 2002; 239: 121-28
6. Dingler A: PhD thesis. 1998; Berlin.
7. Muller RH, Maassen S, Weyhers H and Mehnert W: Phagocytic uptake and cytotoxicity of solid lipid nanoparticles (SLN) sterically stabilized with poloxamine 908 and poloxamer 407. J Drug Target 1996; 4: 161-70.
8. Wang JX, Sun X, Zhang ZR. Eur. J. Pharm. Biopharm. 2002; 54: 285-90.
9. Gohla SH and Dingler A: Pharmazie 2001; 56: 61-3.
10. Muller RH and Runge SA: Harwood Academic Publishers1998; 219-34.
11. Schwarz C, Mehnert W, Lucks JS and Muller RH: Solid lipid nanoparticles for controlled drug delivery. J. Control. Rel. 1994; 30: 83-96.
12. Nair R et al.: Recent Advances in Solid Lipid Nanoparticle Based Drug Delivery Systems J Biomed Sci and Res. 2011; 3(2): 368-384
13. Siekmann B and Westesen K: Submicron-sized parenteral carrier systems based on solid lipids. Pharmacol. Lett. I. 1992; 123-126.
14. Jores K, Mehnert W, Drechsler M, Bunjes H, Johann C and Mader K: Investigations on the structure of solid lipid nanoparticles (SLN) and oil-loaded solid lipid nanoparticles by photon correlation spectroscopy, field-flow fractionation and transmission electron microscopy. Journal of Controlled Release 2004; 95: 217-227.
15. Schoè N, Zimmermann E, Katzfey U, Hahn H, Muèller RH and Liesenfeld O: Effect of solid lipid nanoparticles (SLN) on cytokine production and the viability of murine peritoneal macrophages. J.Microencapsul.2000;17:639-50.
16. Müller RH, Mäder and Gohla S: Solid lipid nanoparticles (SLN) for controlled drug delivery – a review of the state of the art. European J. Pharm. & Biopharm. 2000; 50: 161-177.
17. Trotta M, Debernardi F and Caputo O: Preparation of solid lipid nanoparticles by a solvent emulsification-diffusion technique. Int. J. Pharm. 2003; 257: 153-60.
18. Lippacher A, Muller RH and Mader K: Semisolid SLN dispersions for topical application: Influence of formulation and production parameters on viscoelastic properties on viscoelastic properties. Eur. J. Pharm. Biopharm. 2002; 53: 155-160.
19. Jani PU, Halbert GW and Langridge J: J Pharm Pharmacol, 1990; 42: 821-6.
20. Shidhaye SS, Vaidya R, Sutar S, Patwardhan A and Kadam V: J Current Drug Delivery 2008; 4: 324-331.
21. Mishra H, Mishra D, Mishra PK, Nahar M, Dubey V and Jain DK: Evaluation of solid lipid nanoparticles as carriers for delivery of Hepatitis B surface antigen for vaccination using subcutaneous route. J Pharm Pharmaceut Sci. 2010; 13(4): 495-509.
22. Schubert MA and Muller-Goymann CC: Solvent injection as a new approach for manufacturing lipid nanoparticles– evaluation of the method and process parameters. Eur J Pharm Biopharm 2003; 55(1): 125-131
23. Ruckmani K, Sivakumar M and Ganesh kumar PA: J Nanosci Nanotechnol 2006; 6: 2991-5.
24. Pandey R and Khuller GK: Solid lipid particle-based inhalable sustained drug delivery system against experi-mental tuberculosis. Tuberculosis. 2005b; 85(4): 227-234.
25. Luo Y, Chen D, Ren L, Zhao X and Qin J: Solid lipid nanoparticles for enhancing vinpocetine's oral bioavaila-bility. J Control Release 2006; 114(1): 53-59.
26. Meyer E and Heinzelmann H: Scanning force microsco-py. In: Wiesendanger R, Guntherodt HJ, editors. Scanning tunneling microscopy II, Surface science. New York: Springer Verlag 1992; 99-149.
27. Gaumet M, Vargas A, Gurny R and Delie F: Nanoparticles for drug delivery: The need for precision in reporting particle size parameters. European Journal of Pharmaceutics and Biopharmaceutics 2008; 69: 1-9.
28. Ekambaram P, Sathali AH and Priyanka K: Solid Lipid Nanoparticles: A Review. Scientific Reviews and Chemical. Communication 2012; 2 (S1): 80-102.
29. Chen DB, Yang TZ, Lu WL and Zhang Q: In vitro study of two types of long circulating solid lipid nanoparticles containing paclitaxel. and Pharm. Bulletin. 2001; 49: 1444-1447.
30. Mühlen A and Mehnert W: Drug release and release mechanism of prednisolone loaded solid lipid nanoparticles. Pharmazie 1998; 53:
31. Araújo J, Gonzalez E, Egea MA, Garcia ML and Souto EB: Nanomedicines for ocular NSAIDs: safety on drug delivery. Nanomedicine: Nanotechnology, Biology, and Medicine 2009; 45: 56-64.
32. Mandawgade SD and Patravale VB: Development of SLNs from natural lipids: Application to topical delivery of tretinoin. International Journal of Pharmaceutics 2008; 363: 132-138.
33. Shenoy VS, Vijay IK and Murthy RS: J Pharm Pharmacol, 2005; 57: 411-22.
34. Wu L, Tang C and Yin C: Pharmazie 2010; 65: 493-9.
35. Yang SC, Lu LF, Cai Y, Zhu JB, Liang BW and Yang CZ: J Control Release 1999; 59: 299-307.
36. Shahgaldiana P, Quattrocchia L, Gualberta J, Colemana AW and Goreloff P: Eur J Pharm and Biopharm. 2003; 55: 107-13.
37. Wissing SA, Kayser O and Muller RH: Adv Drug Deliv Rev. 2004; 56: 1257-72.
38. Pandey R, Sharma S and Khuller GK: Oral solid lipid nanoparticle-based antitubercular chemotherapy. Tubercu-losis 2005a; 85(5-6): 415-420.
39. Rudolph C, Schillinger U, Ortiz A, Tabatt K, Plank C and Muller RH: Pharmaceutic Res 2004; 21: 1662-9.
    

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    How to cite this article:

    Raut ID, Doijad RC and Mohite SK: Solid lipid nanoparticles: A promising drug delivery system. Int J Pharm Sci Res 2018; 9(3): 862-71. doi: 10.13040/IJPSR.0975-8232.9(3).862-71.

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