A Review on Solid Lipid Nano Particles (SLNS)

 

Vinay Kumar1*, Anurag Kumar Verma2, Dhyan Chandra Yadav2

1Institute of Pharmacy, VBS Purvanchal University, Jaunpur

2Dept. of Computer Applications, VBS Purvanchal University, Jaunpur

*Corresponding Author E-mail: vvermaph@gmail.com

 

ABSTRACT:

SLNs is as of late created strategy, in which the size reaches from 1 to 1000nm particles can use for medication conveyance framework. It is essentially a colloidal transporter. In this survey the most recent innovative work of SLNs as indicated by the cutting edge writing are refered to. The capacity to join drugs into nanocarriers offers another model in medication conveyance that could use for medication focusing on. The proposed system of medication discharge from SLNs is additionally referenced in this audit. The planning procedures for generation of SLNs are examined with dissident portrayal. Fitting systematic strategies for the portrayal of SLNs like photon connection spectroscopy, filtering electron microscopy, differential checking calorimetry are featured. Parts of SLN course of organization and the in vivo destiny of the bearers are likewise examined. More distant more the different application with appropriate model are likewise examined.

 

KEYWORDS: Colloidal medication bearers, Homogenization, TEM, PCS, Solid lipid nanoparticles, Production methods, Targeting.

 

 

 

1. INTRODUCTION:

The new wildernesses like liposome, strong lipid nano particles have demonstrated improve medicate conveyance. Nano particles are 10-1000nm territories strong colloidal medication transporters in which the dynamic moiety broke down, captured or adsorbed – appended towards its surface1. As of late little atomic weight drugs, macromolecules (protein, peptide, gens) was defined in nano specific range, to give them great enzymatic stability2. Strong lipid nano particles (SLNs) upgrade the bioavailability of medications like eg: cyclosporine A3. Due its profile degradable property its is less cyto harmful. SLNs planned in different application roots like parental, oral, dermal, visual, rectal4.

 

Advantages:

1    Astounding biocompatible with high target explicit activity.

2    Effectively scale up is conceivable and solidness is great.

3    Insurance of synthetically obligated medications from bio debasement in gut and touchy particle from external condition.

4    Better power over discharge energy of embodied compound.

5    Compare to other bio polymeric particle SLNs are exceptionally simple to deliver. The crude materials are similar of emulsions.

6    With uniting monoclonal neutralizer it could act like a multifunctional dose structure.

7    Lyophilisation is conceivable.

 

Disadvantages:

1    It has poor medication stacking limit.

2    Dubious gelation propensity.

3    Uneven energy for polymeric progress.

4    Molecule development is seen amid capacity.

5    Moderately higher water substance of the scattering (70-99.9%) 5

 

2. METHOD FOR PREPARATION:

SLNs made up of strong lipid emulsions. Where Lipids, for example, Triglycerides, Tri-stearin, Glycerol monostearate (GMS), Waxes (cetylpalmitate), Steroids (cholesterol), Tripalmitin, Cocao spread, Monostearin, Lecithin, Tribehenate, Trimyristin are utilized. Poloxamer 188, Tween 80, PVA likewise can be utilized as a surfactant. Emulsifiers, for example, Pluronics F68,127 can anticipate molecule agglomeration.

SLNs are set up from lipid, emulsifier and water/dissolvable by utilizing various strategies and are talked about beneath.

 

1    High weight homogenization

A   Hot homogenization

B   Cold homogenization

 

2    Ultrasonication/fast homogenization

A   Test ultrasonication

B   Shower ultrasonication

 

3    Dissolvable vanishing strategy

4    Dissolvable emulsification-dissemination strategy

5    Supercritical liquid strategy

6    Microemulsion based strategy

7    Splash drying strategy

8    Twofold emulsion strategy

9    Precipitation strategy

10  Film-ultrasound scattering.

11  Membrane contactor strategy.

12  Dissolvable infusion strategy

 

2.1. High weight homogenization:

It pushes the fluid with high weight (100-200bar) through an empty hole of somewhere in the range of couple of microns. With about 100Km/h rate and with high thickness the liquid quickens to an extremely short separation. Very high weight pressure and cavitations power interfere with the molecule down to submicron estimate go with 5-40% lipid content. In HPH two distinct methodologies with same rule were established6.

 

A. Hot homogenization: Homogenization of an emulsion can be completed in over the dissolving purpose of the fluid. With the assistance of high – share blending gadget, a pre-emulsion of the medication

 

stacked lipid liquefy and the watery emulsifier stage (same temperature) is gotten. The HPH of pre emulsion can be completed over the fluid softening point. Because of diminishing consistency of internal period of emulsion in high temperature, molecule size would be lower 7. Expanding the homogenization weight or the quantity of cycles regularly results in an expansion of the molecule measure because of high active vitality of the particles. The potential hindrances of this strategy is, high temperature shell may doctorate tranquilize content. Every so often 3-5 homogenization cycle at weight of 500-1500bar are used 8, 9.

 

Fig1: Solid lipid nanoparticles preparation by hot homogenization process.

 

B. Cold homogenization:

Cold homogenization has been created to over-come the temperature related corruption issues, loss of medication into the watery stage and apportioning related with hot homogenization technique. Unusual polymeric advances of the lipid because of multifaceted nature of the crystallization venture of the nanoemul-sion bringing about a few changes or potentially super cooled melts. Here, medicate is fused into liquefied lipid and the lipid liquefy is cooled quickly utilizing dry ice or fluid nitrogen. The strong material is ground by a mortar factory. The readied lipid microparticles are then scattered in a chilly emulsifier arrangement at or beneath room temperature. The temperature ought to be controlled adequately to guarantee the strong condition of the lipid amid homogenization. Notwithstanding, contrasted with hot homogenization, bigger molecule sizes and a more extensive size appropriation are common of cold homogenization tests9,10

 

Fig. 2: Solid lipid nanoparticles preparation by cold homogenization process.

2.2. Ultrasonication/high speed homogenization:

The promising points of interest in this techniques is that the types of gear utilized is normally accessible in lab scale. More extensive size circulation running in micron extend is the primary inconveniences. Potential metal sullying and ill-advised soundness amid capacity like molecule development, aggregation of molecule are significant downside11.

 

2.3. Solvent evaporation:

Dissolvable dissipation technique is likewise used to get ready SLNs. The lipophilic material is break down in a water miscible natural dissolvable (eg; cyclohexane) and emulsified in watery stage. Upon dissipation nanoparticles scattering is framed by precipitation of the lipid in the watery medium by giving the nanoparticles of 25nm mean size. The arrangement was emulsified in a fluid stage by high weight homogenization. The natural dissolvable was expelled from the emulsion by vanishing under diminished weight (40–60 mbar). The principle preferences of this framework is it's a nonstop procedure 13 7

 

Fig. 3: Schematic representation of solvent evaporation technique

 

2. 4. Solvent emulsification-diffusion method:

Shirking of warmth is the most criticalness points of interest of this technique. Based upon the emulsion utilized and lipid fixation, the mean molecule is trustworthy. SLNs with 30-100nm size fury, could be conceivable to figure in this strategy. In this system lipid grid is disintegrate in water–immiscible natural dissolvable, and emulsification is occurred in watery phase12. Nano specific scattering framed by precipitation of lipid in fluid media while keeping up low weight and vanishing13.

 

Fig. 4: Schematic representation Solvent emulsification-diffusion method

 

2. 5. Supercritical fluid method:

A liquid is named overly basic when its weight and temperature surpass their separate basic esteem, by which the capacity of the liquid to break down mixes increments.The fast extension of supercritical arrangement (RESS), molecule gas immersed arrangements (PGSS), airborne dissolvable extraction dissolvable (ASES), supercritical liquid extraction of emulsions (SFEE) are the different procedure used to detail SLNs in this method .In this system evasion of the dissolvable, dry power particles, rather than suspension, little weight and temperature condition are the potential points of interest. Carbon dioxide arrangement is a superb decision as a dissolvable for this technique14,15.

 

2.6 Micro emulsion based method:

Gasco and organization (1997) created SLNs dependent on weakening of smaller scale emulsion. Smaller scale emulsion was an optically straightforward blend at 65-70°c or a marginally somewhat blue arrangement which is regularly made out of low liquefying lipid, emulsifier (s), Co-emulsifier and water.

 

Fatty acid: stearic acid,

 

Emulsifier: polysorbate 60, polysorbate 20, soyaphosphatydylcholine and taurodeoxycholic corrosive sodium salt,

 

Co-emulsifiers: butanol, sodium monooctylphosphate and water was utilized to get ready SLNs. The hot smaller scale emulsion is scattered in virus water (2-3ºC) under blending. 1:25 to 1:50 is the run of the mill volume proportion of the hot smaller scale emulsion to the virus water. The weakening procedure is enhanced by the creation of the miniaturized scale emulsion 16,17,18. The SLNs scattering can be utilized as a crushing liquid for moving into strong item like tablets and pellets by granulation process .Too a lot of water should be expel to acquire low particles content .The dissolvable which have the powerlessness to appropriate with in fluid stage (eg. acetone) were increasingly ideal for SLNs detailing. More lipid dissolvable produce bigger molecule estimate. Thinking about small scale emulsions, the temperature slope and pH esteem fix the item quality notwithstanding the structure of the smaller scale emulsion. High temperature slopes encourage fast lipid crystallization and avert total19,20.

 

Step1

Step 2

Fig. 5: Microemulsion method

 

2.7. Spray drying method:

This is conceder to be the best elective strategy for lyophilisation method. Lipid with softening point above 70ºC were best reasonable for this strategy 19. The best outcomes were acquired with SLN convergence of 1% in an answer of trehalose in water or 20% trehalose in ethanol-water blend19.

 

2.8. Double emulsion method:

In this strategy medicate is at first disintegrate in fluid stage and after that emulsified in softened lipid stage. The essential emulsion was settled endless supply of stabilizer eg: gelatine, poloxamer-407. At that point this balanced out essential emulsion was scattered in fluid stage containing hydrophilic emulsifier21. From that point, the twofold emulsion was mixed and was secluded by filtration. The zidovudine stacked SLNs were set up with stearic corrosive by procedure of w/o/w twofold emulsion dissolvable vanishing strategy utilizing 32 factorial structure and various triglycerides alone and in various mixes, with/without stearic corrosive. Two working factors, measure of lipid and polyvinyl liquor focus were found to have huge impact on the molecule size and ensnarement productivity of the SLN 22. Twofold emulsion system keeps away from the need to dissolve the lipid for the planning of peptide-stacked lipid nanoparticles and the outside of the nanoparticles could be changed so as to sterically balance out them by methods for the consolidation of a lipid/- PEG subsidiary. Sterical adjustment altogether improved the obstruction of these colloidal frameworks in the gastrointestinal liquids23.

 

2.9. Precipitation technique:

In natural dissolvable (eg: chloroform, dichloromethane) glycerides are disintegrated. The arrangement further emulsified in fluid stage. After vanishing the lipid would be hastened out as a SLNs 7.

 

 

 

2.10. Film-ultrasound dispersion:

After decompression, turn and dissipation of the natural arrangements comprising of lipid and medication, a lipid film is framed, in that include watery arrangement which incorporates the emulsions. Utilizing the ultrasound with the test to diffuser finally, the SLN with the little and uniform molecule measure is framed.

 

2.11. Membrane contactor technique:

In this strategy the fluid stage was squeezed at a temperature over the dissolving purpose of the lipid through the film pores permitting the arrangement of little beads. The watery stage was blended persistently and courses incidentally inside the film module, and breadths away the beads being framed at the pore outlets. SLNs were shaped by the cooling of the readiness at the room temperature. Nutrient E stacked SLN are readied utilizing a film contactor system to permit extensive scale generation and their security is promising24.

 

2.12. Solvent injection technique:

It depends on lipid precipitation from the disintegrated lipid in arrangement. In ethanol, CH3)2CO, isopropano the strong lipids were break up. The lipid blend were then add to the fluid stage drop by drop utilizing infusion needle containing with or without surfactant. Dispersion was then sifted to isolate abundance lipid .Surfactant in watery stage produce great SLNs,  more distant its gives broad strength to the framework. Dissolvable infusion lyophilization technique was utilized to get ready cinnarizine SLNs, a lipophilic medication. SLNs bearing oxybenzone was likewise arranged by ethanol infusion strategy to improve its viability as sunscreen and were described for molecule estimate, polydispersity file, zeta potential and surface morphology 25, 26, 27. The schematic portrayal of dissolvable infusion technique was appeared in figure 6.

 

Table1: Different methods for preparation of SLNs

Method

Drug

Lipid

Reference

Hot homogenization

Flurbiprofen

Trimyristin

28

Modified coacervation

Gatifloxacin

Tristearin

29

Ultrasonication or high speed homogenization

Cryptotanshinone

Compritol 888 ATO

30

Double emulsion technique

Zidovudine

Tripalmitin

31

Supercritical fluid technology

Indomethacin

Tripalmitin

32

Cold homogenization

vinorelbine itartrate

Glyceryl monostearate

33

Solvent emulsification-evaporation technique

Oridonin

Stearic acid

34

 

 

Fig 6: Solvent injection technique

 

Secondary Production approaches:

Freeze drying:

The nano suspension was lyophilized to dry powder to avert its debasement. The cryoprotectants are the substances added with the definition to avert basic harms that might be brought about by abrupt and snappy procedure of solidifying. The states of the stop drying process and the evacuation of water advance the accumulation among SLNs. Bhoga Bhagya et al. Examined the impact of fructose and trehalose as cryoprotectant in various detailing of SLNs of methotrexate. Cryoprotectants were taken in 2% and 15% included the chilly fluid medium. Appropriateness of the cryoprotectants was controlled by the reconstitution conduct with refined water.

 

3. Types Drug incorporation models of SLNs:

In view of the solvency, miscibility of the medication in lipid soften, the medication stacking is trustworthy on SLNs. moreover synthetic and physical structure of the strong lattice, polymeric period of the lipid material likewise impact the medication discharge.

 

Figure 7: Diagrammatic representation for drug incorporation models.

 

Medication is molecularly scattered in lipid grid when SLN is set up by chilly homogenization. In Drug-advanced shell model the strong lipid center structures upon recrystalization. Medication advanced center model: Cooling the nanoemulsion prompts a super immersion of the medication which is broken up in the lipid dissolve prompts recrystalization of the lipid 35, 36.

 

3.1. Drug incorporation and loading capacity:

Lipids like triglyceride, greasy acids, steroids, waxes, emulsifier (anionic and cationic) are in charge of shifting of the molecule measure, sedate stacking limit, and size dispersion of SLNs. The different elements components of deciding the stacking limit of the medication in the lipids rely on following factors37.

·       Chemical and physical structure of the strong network of lipid.

·       Proper dissolvability of the softened lipids.

·       Proper blending of the medication in dissolved lipid.

·       Polymorphic phase of lipid materials.

 

To improve the dissolvability in lipid soften of the medication one must can utilize some great solubilises. The nearness of mono and diglycerides lipids used to advance medication solubilisation38

 

3.2. Determinations of entrapment efficiency:

Medication capture effectiveness influenced the discharge normal for medication atom .After partition of ensnared tranquilize from the SLNs, the measure of the medication which is epitomize per unit weight of nano molecule is resolved . The partition of medications from SLNs can be done by utilizing strategy called ultracentrifugation, centrifugation, filtration or gel pervasion chromatography39.

 

                                             Mass of drug in nanoparticles

% Drug cntrapment efficiency = --------------------------------------- x100

                                           Mass of drug in formulation

 

3.2.1 Centrifugation filtration: 

With present day centrifugation procedure,  channels like ultra free utilized in this technique .The level of embodiment can be dictated by discovering the measure of medication staying in the supernatant of SLNs suspensions after ultra/centrifugation. Disintegration and HPLC examines could be the conceivable method to decided the medication content.

 

4. Principles of drug release from SLNs40,41:

The drug release from the nanoparticle is as follows.

1    Drug release and partition co-efficient is reversely proportional .’

2    Optimum surface area due to nano meter size rang of the particles gives higher drug release .

3    Formation of lipid matrix by  homogeneously disperse technique leads to slow drug release .

4    Formation of lipid –drug crystals decrease the drug release .

 

4.1. Stability:

Gelation marvels, increment in molecule sizes and medication removal from the lipid transporter are the serious issues of capacity steadiness. The change of the lipid liquefy to lipid precious stones results in an expansion of molecule surfaces, a diminishing of the stacking limit of the lipid and in this way, it prompts expanded steadiness issues.

 

 

5.Measurement of drug release from SLNs:

The various method popularly used in vitro release of the drug are:

1    Diffusion with artificial or biological membrane.

2    Dialysis bag diffusion technique.

3    Reverse dialysis bag technique.

4    Centrifugal ultra filtration.

 

5.1. Ex vivo model to determining permeability across the gut:

Ahlin et.al, researched on the movement of enalaprilat SLNs over the rate jejunum. 20-30cm distal from pyloric sphincter was taken for the specific examinations. comparative investigations has completed by zhi lu et at; by taking 10 cm long portions of duodenum.

 

6.Analytical characterization of SLN42,43,44:

6.1. Measurement of particle size and zeta potential:

The physical dependability of SLNs relies upon their molecule estimate. Photon connection spectroscopy (PCS) and Laser diffraction (LD) are most noteworthy strategy used to decide molecule measure. PCS or dynamic light dissipating, measure the vacillation of force of dispersed light which is brought about by molecule development. In this system one can appraise few nano meter to 3 micron size scope of particles. PCS is generally amazing instrument to identified and portray nanoparticle, anyway expansive particles is not really distinguished by this strategy. Electron magnifying instrument appended with PCS and LD, to evaluate direct data of particles. Zeta potential permits to foresee the solidness of the detailing amid capacity. Zeta potential analyser or Zetameter used to appraise the zeta capability of suspended SLNs. Before estimating ZP, the SLNs scattering are weakened 50-overlap with unique scattering medium. Higher estimation of zeta potential may prompt deaggregation without steric acid (stabilizer) or hydrophilic limbs.

 

6.2Electrone microscope:

Transmission electron microscope (TEM), and Scanning electron microscope (SEM) provides way to directly observed nano particles. SEM is widely used for morphological examination.

 

6.3. Atomic force microscopy:

In this procedure, a test tip with nuclear scale sharpness is rastered over an example to create a topological guide dependent on the powers at play between the tip and the surface. The test can be hauled over the example (contact mode), or permitted to drift simply above (non contact mode), with the precise idea of the specific power utilized serving to recognize among the sub systems. That ultra-high goals is realistic with this methodology, which alongside the capacity to outline test as indicated by properties notwithstanding size, e.g., colloidal fascination or protection from misshapening, makes AFM a significant device (Mukherjee et al., 2009).

 

6.4. Dynamic light scattering (DLS):

Browniar movement is a viable element of colloidal scattering (SLNs). In Browniar movement lights begin dissipating. The technique called semi versatile light dispersing (QELS) or Dynamic light dissipating (DLS), the force of the dissipated light of nano molecule were estimated in microsecond time scale. At last it produce an auto redress factor. The potential points of interest of this strategy is that it is dreary and has its affectability to submicron particles.

 

6.5. Static light scatterings (SLS)/Fraunhofer difference:

The light dispersed from an answer of particles is gathered and refered to into an electromagnetic conditions, where molecule measure is the essential variable. This strategy need more tidiness then DLS.

 

6. 6 Differential scanning calorimetric (DSC):

The geometric dispersing of radiation from precious stone planes inside a strong permit the nearness or nonattendance of the previous to be resolved in this way the level of crystallinity to be evaluated. DSC can be utilized to decide the nature and the speciation of crystallinity inside nanoparticles through the estimation of glass and softening point temperature. The geometric dispersing of radiation from gem planes inside a strong permit the nearness or nonappearance of the previous to be resolved in this manner the level of crystallinity to be evaluated. DSC can be utilized to decide the nature and the speciation of crystallinity inside nanoparticles through the estimation of glass and dissolving point temperature.

 

6.7. Acoustic methods:

Another group approach, acoustic spectroscopy, measures the lessening of sound waves as a methods for deciding size through the fitting of physically significant conditions. Likewise, the wavering electric field produced by the development of charged particles affected by acoustic vitality can be recognized to give data on surface charge.

 

6.8. Nuclear magnatic resonance (NMR):

Both size and quantitative nature of the nano particles can be measure by NMR.

 

7. Application of SLNs:

7.1. SLNs for parental applications:

Because of its great medication stockpiling capacity after stop drying and comprising physiologically well bearable fixings SLNs are truly reasonable in parental use .Best methodology is its size, it can without much of a stretch course in small scale vascular framework and avert macrophage take-up (in the event of hydrophilic coating)45.In viral and non viral quality qualities conveyance it is widely utilized .In the treatment of disease cationic SLNs have potential advantage in focusing on carcinogenic cells. Treatment of focal sensory system infections, for example, mind tumors, AIDS, neurological and mental disarranges is regularly obliged by the powerlessness of strong medications to pass blood cerebrum boundary (BBB). Hydrophilic covering of colloids improves the vehicle of these through BBB and tissue distribu-tion (Kreuter 2001; Wang et al., 2002). Fundaro et al, 2000, arranged doxorubicin stacked stealth and non-stealth SLN and saw that the stealth nanopar-ticles were available in blood at higher focuses than non-stealth SLN after 24 h following intraven-ous organization46.

 

7.2. Solid lipid nanoparticles in cancer chemotherapy:

In ongoing time chemotherapeutic medications are incomprehensibly exemplify in SLNs. Lili Qian et al. (2013) created cationic center shell nanoparticles with carmustine cantined with o6– Benzylguanine shell for glioma treatment. On the opposite side. Xin-Hua Tian et al. (2011)47 Did inquire about on upgraded cerebrum focusing of temozolomide52 in polysorbate-80 covered polybutylcyanoacrylate nanoparticles. In both the cases upgrade of bioavailability and less cyto poisonous quality was watched for chemothaputic specialists. The fast expulsion of colloidal particles by the macrophages of the RES is a noteworthy obstruction to focusing on tissues somewhere else in the body, for example, bone marrow and strong tumors. Improved strength of medications, exemplification of chemotherapeutic specialists of differentiated physicochemical properties, upgraded sedate viability, improved pharmacokinetics and less in-vitro poisonous quality are the significant highlights of SLN which make them a reasonable transporter for conveying chemotherapeutic drugs 51.

 

7.2.1. SLN as targeted carrier for anticancer drug to solid tumor:

Tamoxifen is an anticancer medication consolidated in SLN to delay the arrival of medication after IV organization in bosom malignant growth. Tumor focusing on has been accomplished with SLN stacked with medications like methotrexate and camptothecin49, 50.

 

7.2.2. SLN in breast cancer and lymph node metastases:

Mitoxantrone SLN local injections were formulated to reduce the toxicity and improve the safety and bioavailability of the drug48.

 

 

7.3 Solid lipid nanoparticles for targeted brain drug delivery:

Molecule measure scope of under 50nm could be produce useful impact on mind focusing on. Smaller size more often than not helps for take-up in RE framework. To the extent cerebrum take-up is concern, probably system is endocytosis, by the endothelial cells coating of blood vessels. SLNs-interceded sedate transport to the cerebrum relies upon the over covering of the particles with polysorbate 80. Over covering with these materials appears lead to the adsorption of apolipoprotein E from blood plasma on to the nanoparticle surface. The particles at that point appear to mirror low thickness lipoprotein (LDL. Particles at that point communicate with the LDL receptor prompting their take-up by the endothelial cells of mind. In an examination to beat the constrained access of the medication 5-fluoro-2'- deoxyuridine (FUdR) to the mind, 3',5'- dioctanoyl-5-fluoro-2'- deoxyuridine (DO-FUdR) was blended and consolidated into strong lipid nanoparticles (DOFUdR-SLN)53. The surfactant covered poly (alkylcyanoacrylate) nanoparticles explicitly intended for cerebrum focusing on is given by underlining the exchange of this innovation to strong lipid networks51.

 

7.4. SLN applications for improved delivery of antiretroviral drugs to the brain:

Current antiretroviral drugs (ARVs) regularly neglect to viably lessen the HIV viral: load in the cerebrum. This, to some extent, is because of the poor transport of numerous ARVs, specifically protease inhibitors, over the blood cerebrum hindrance (BBB) and blood-cerebrospinal liquid boundary (BCSBF). Studies have demonstrated that nanocarriers including polymeric nanoparticles, liposomes, strong lipid nanoparticles (SLN) and micelles can build the neighborhood tranquilize focus angles, encourage medicate transport into the cerebrum by means of endocytotic pathways and repress the ATP-restricting tape (ABC) transporters communicated at the obstruction destinations. By conveying ARVs with nanocarriers, huge increment in the medication bioavailability to the mind is relied upon to be accomplished.

 

7.5. SLNs for Nasal application54,55:

In non intrusive system the nasal defeat is a best option. Prodrug derivatization stacking with medication and peptides and proteins can be defined in SLNs measurements frames. In an ongoing report, covering polymeric nanopar-ticles with PEG gave promising outcomes as antibody transporters (Vila et al., 2004). The job of PEG covering of polylactic corrosive nanoparticles in improving the trans mucosal transport of the typified bioactive particle answered to be effective by Tobio et al, 1998. This idea can be valuable for strong lipid nanoparticles.

7.6. SLNs for respiratory applications:

Since dividers of the alveoli in profound lungs are very slight quick medication assimilation by aerosolization of medications (1-3 micro. meter) happens. In lung malignancy treatment SLNs assumes an emotional job. Radio– marked SLNs assumes a critical job in lymphatic take-up by inhalation. In late advancement, rafampicin, isoniazid, pyrazinamide, was set up in SLNs in size scope of 1.1-2.1 micro. meter, was nebulized into guinea pig for direct aspiratory conveyance. It was seen that SLNs stacked enemy of tubercular medication improves tranquilize bioavailability and dose recurrence56,57.

 

7.7. SLNs for ocular application:

Biocompatibility, mucoadhesive ness, Iso ophthalmic pH, drag out corneal occupant time, of SLNs ad lib visual focusing on. cavalli et al; 2002 created tobramycine SLNs for focusing on rabbit eyes. cavalli et al; 2005 again create SLNs of pilocarpine, a medication utilized in glaucoma. Both the cases he discovered great bioavailability in fluid amusingness58.

 

7.8 SLNs for topical application58,59,60:

Analysts have detailed seriously on the topical use of SLN. Amid the most recent couple of years, SLN and NLC have been contemplated with dynamic mixes, for example, Vitamin E (Dingler et al., 1999), tocopherol acetic acid derivation (Wissing and Muller 2001), retinol (Jenning et al., 2000), ascorbyl palmitate (Uner et al., 2005a and 2005b), clotrimazole (Souto et al., 2004), triptolide (Mei et al., 2003), phodphyllotoxin (Chen et al., 2006) and a nonsteroidal antiandrogen RU 58841 (Munster et al., 2005) for topical application. A totally new, as of late found zone of applica-tion is the utilization of SLN in sun-defensive creams (Waghmare et al., 2012).

 

7.9. Stealth nanoparticles:

The fundamental points of interest of this framework is high freedom from resistant framework. Antibody marked stealth nanoparticles have great medication conveyance property in influenced site. Stealth nanoparticle is tried on creatures.

 

7.10. SLNs as cosmeceuticals:

SLNs are powerful in planning sun screen defensive. Occlusive properties, increment in skin hydration, altered discharge, increment of skin entrance and evasion of foundational take-up. The initial two corrective items containing lipid nanoparticles were acquainted with the market in 2005.

 

7.11. SLN applied to the treatment of malaria:

The principle disservices of customary chemotherapeutic medications in intestinal sickness treatment is advancement of multi sedate obstruction, and non explicit focusing to entomb cell parasites. Nanosized bearers have been accepting exceptional consideration with the point of limiting the symptoms of medication treatment, for example, poor bioavailability and the selectivity of medications. A few nanosized conveyance frameworks have officially demonstrated their viability in creature models for the treatment and prophylaxis of intestinal sickness62.

 

8. CONCLUTION:

The principle points of interest of SLNs are expansive scale up is conceivable and medication can be compelling with in less portion joining. Also SLNs particles are in sub micron estimate because of this, progressively powerful surface region and great bioavailability is conceivable. Ongoing examinations on mind focusing on, lungs focusing on,ophthalmic conveyance furnishes huge cell take-up of medications with less cyto poisonous quality . The development of fluid precious stones and definition with dinner cooled liquefy produces strength issue, which could be the significant difficulties for researchers. NMR, ESR and synchrotron illumination will help the medication nanosuspensions exist together in the example. Lamentably, these perspectives have not generally been considered and the end 'medicate joining' in the SLN writing is regularly deceptive. In vito and in vivo examinations must be diverted to comprehend appropriate elements and sub-atomic mark movement of SLNs.

 

9. REFERENCES:

1.        Kreuter, J. (1991). Peroral administration of nanoparticles. Adv Drug Del Rev 7: 71-86.

2.        Chowdary, K.P.R., Rao, AS. (1997). Nanoparticles as drug carriers. Indian Drugs 34(10):549-56.

3.        Muller, R.H., Runge, S.A., Ravelli, V., Thünemann, A.F., Mehnert, W., Souto, E.B. (2008) Cyclosporine-loaded solid lipid nanoparticles (SLN): drug-lipid physicochemical 392 interactions and characterization of drug incorporation. Eur J Pharm Biopharm: 68(3): 535-544.

4.        Mulla, J.S., Khazi, I.M., Jamakandi, V.G. (2010). Solid lipid nanoparticles: Potential IJNDD 2(3): 82-87.

5.        Schwarz, C., Mehnert, W., Lucks, J.S., Muller, R.H. (1994). Solid lipid nanoparticles (SLN) for controlled drug deli-very I. Production, characterization and sterilization. J Control Release 30(1): 83-96.

6.        Mehnert, W., Mader, K. (2001) Solid lipid nanoparticles: Production, characterization, applications. Advanced Drug Delivery Review. 47: 165-196.

7.        Krishna Sailaja A, Amareshwar P, Chakravarty P. Formulation of solid lipid nanoparticles and their applications. CPR 2011, 1(2), 197-203.

8.        Ahlin P, Kristl J, Kobar S. Optimization of procedure parameters and physical stability of solid lipid nanoparticles in dispersion. Acta Pharm. 1998, 48, 257-67.

9.        Jahnke S. The theory of high pressure homogenization, in: Muller RH, Benita S, Bohm B. editors. Emulsions and nanosuspensions for the formulation of poorly soluble drugs, Stuttgart Medpharm Scientific Publishers. 1998, 77-2005

10.      Ekambaram, P., Abdul Hassan Sathali, A., Priyanka, K. (2012). Solid Lipid Nanoparticles: A Review. Sci Revs Chem Commun 2(1): 80-102.

11.      Elldem, T., Speiser, P., Hineal, A. (1991). Optimization of spray-dried and congealed lipid microparticles and cha-racterization of their surface morphology by scanning electron microscopy. Pharm Res 8: 47-54.

12.      Muller, R.H., Mäder, K., Gohla, S.H. (2000) Solid Lipid Nanoparticles For Controlled Drug Delivery- A Review of the State of the art. Eur J Pharm Bio Pharm 50(1): 161-177.

13.      Trotta, M., Debernardi, F., Caputo, O. (2003) Preparation of Solid Lipid Nanoparticles by a solvent emulsification-diffusion technique. Int J Pharm. 257: 153-160.

14.      Chen YJ, Jin RX, Zhou YQ, Zeng J, Zhang H, Feng QR. Zhongguo Zhong Yao Za Zhi 2006, 31, 376-9.

15.      P. Chattopadhyay, B.Y. Shekunov, D. Yim, D. Cipolla, B. Boyd, S. Farr, Advanced Drug Delivery Reviews 2007, 59, 444–53.

16.      Gasco MR. United State Patent.US 188837, 1993.

17.      Gasco MR. Pharm Tech Eur, 1997, 9, 52-58.

18.      Kuo Y.-C., Chen H. International Journal of Pharmaceutics, 2009; 365, 206-10

19.      Mueller B.W, Mikroemulsionen als neue Wirkstoff-Traegersysteme, in: R.H. Mueller, G.E. Hildebrand (Eds.), Pharmazeutische Technologie., 1998; pp. 161-168.

20.      Waghmare AS, Grampurohit ND, Gadhave MV, Gaikwad DD, Jadhav S. Solid lipid nanoparticles. A promising drug delivery System IRJP. 2012, 3(4), 100-107.

21.      Li, Z., Li, X., Zheng, L., Lin, X., Geng, F., Yu, L. (2010) Bovine serum albumin loaded solid lipid nanoparticles prepared by double emulsion method. Chem Res Chinese Universities 26(1):136-141.

22.      Singh S, Dobhal AK, Jain A, Pandit JK, Chakraborty S., Chem Pharm Bull, 2010, 58, 650-5.

23.      M Garcıa-Fuentes, D Torres, MJ Alonso, Biointerfaces. 2002, 27, 159-68.

24.      Catherine Charcosset, Assma El-Harati, Hatem Fessi., Journal of Controlled Release, 2005, 108, 112–120.

25.       MA Schubert, CC Muller-Goymann, Eur J Pharm Biopharm. 2003, 55, 125–31.

26.      Wang T, Wang N, Zhang Y, Shen W, Gao X, Li T. Colloids Surf B Biointerfaces. 2010, 79, 254-61.

27.      Arvind Gulbake, Aviral Jain, Piush Khare, Sanjay K. Jain, Journal of Microencapsulation, 2010; 27, 226–233.

28.      Bhaskar K. Anbu J Ravichandiran V. Venkateswarlu V. and Rao Y.M, Lipids in health and disease, 2009, 6.

29.      Motwani, S.K., Chopra, S., Talegaonkar, S., Kohli, K., Ahmad, F.J., Khar, R.K. (2008). Chitosan–sodium alginate nanopar-ticles as submicroscopic reservoirs for ocular delivery: Formulation, optimization and in vitro characterization. Eur J Pharm Biopharm 68(3): 513-525.

30.      Hu L, Xing Q, Meng J, Shang C. AAPS Pharm Sci Tech. 2010, 11, 582-87.

31.      Singh S, Dobhal AK, Jain A, Pandit JK, Chakraborty S., Chem Pharm Bull, 2010, 58, 650-5.

32.      P. Chattopadhyay, B.Y. Shekunov, D. Yim, D. Cipolla, B. Boyd, S. Farr, Advanced Drug Delivery Reviews 2007, 59, 444–53.

33.      Fu qiang Hu, Jian You, Feng Wan, Fu de Cuib, Yu Sun, Yong-Zhong Du, International Journal of Pharmaceutics 343, 2007, 270–76.

34.      Dianrui Zhang, Tianwei Tan, Lei Gao, Nanotechnology,2006, 17, 5821.

35.      Sinha Ranjan Vivek, Srivastava Saurabh, Goel Honey, Jindal Vinay, Solid Lipid Nanoparticles (SLN’S) – Trends and Implications in Drug Targeting, International Journal of Advances in Pharmaceutical Sciences, volume 2, 2010, 212-238.

36.      Cavalli ER. Marengo L, Rodriguez, Gasco MR, Effects of some experimental factors on the production process of solid lipid nanoparticles, Eur J Pharm Biopharm volume 2, 1996, 110-15.

37.      Sinha Ranjan Vivek, Srivastava Saurabh, Goel Honey, Jindal Vinay, Solid Lipid Nanoparticles (SLN’S) – Trends and Implications in Drug Targeting, International Journal of Advances in Pharmaceutical Sciences, volume 2, 2010, 212-238.

38.      Bhatt Ashvin D, Pethe A M, Lipid Technology- A Promising Drug Delivery SystemFor Poorly Water Soluble Drugs, International Journal Of Pharma Research And Development, volume 1, 2010, 1-11.

39.      Schwarz WC. Mehnert JS, Lucks, Muller RH, Solid lipid nanoparticles (SLN) for controlled drug delivery Production, characterisation and sterilization. J Control Release, volume 3, 1994, 83-96.

40.      Melike Uner, Gulgun Yener, Int. J. Nanomedicine, 2(3), 289-300 (2007).

41.      Annette Zur Mehlen, Cora Schwarz and Wolfgang Mehnart, Eur. J. Pharm. Biopharm., 45, 149-15(1998).

42.      Akanksha Garud, Deepti Singh, Navneet Garud; Solid Lipid Nanoparticles (SLN): Method, Characterization and Applications, International Current Pharmaceutical Journal 2012, 1(11): 384-393 http://www.icpjonline.com/documents/Vol1Issue11/08.pdf.

43.      P. Ekambaram, a. Abdul hasan sathali and k. Priyanka; Solid lipid nanoparticles: a review; sci. Revs. Chem. Commun.: 2(1), 2012, 80-102Issn 2277-2669.

44.      Rahul Nair, K. S. Arun Kumar, K. Vishnu Priya, M. Sevukarajan; Recent Advances in Solid Lipid Nanoparticle Based Drug Delivery Systems; Rahul Nair et al / J Biomed Sci and Res., Vol 3 (2), 2011,368-384.

45.      Wissing, S.A., Kayser, O., Muller, R.H. (2004). Solid lipid nanoparticles for parenteral drug delivery. Adv Drug Deliv Rev 56(9): 1257-1272.

46.      Olbrich, C., Bakowski, U., Lehr, C.M., Müller, R.H., Kneuer, C. (2001). Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA. J Control Release 77(3): 345-55.

47.      Yung-Chih Kuo, Cheng –Te Liang. Inhibition of human brain malignant glioblastoma cells using carmustine-loaded cationic solid lipid nano perticals with surface anti-epithelial growth factor. Biomaterials 32(2011)3340-3350.

48.      Murthy, R.S.R. (2005) Solid lipid nanoparticles as carriers for anti-cancer drugs to solid tumours. Drug Deliv 12: 385-392.

49.      Shenoy VS, Vijay IK, Murthy RS. J Pharm Pharmacol, 2005, 57, 411-22.

50.      Ruckmani K, Sivakumar M, Ganeshkumar PA., J Nanosci Nanotechnol, 2006, 6, 2991-5.

51.      Melike Uner, Gulgun Yener, solid lipid nanoparticles overview, Int. J. Nanomedicine, 2007, 289-300.

52.      Xin-Hua Tian,Xiao-Ning Lin, Feng Wei, Wei Feng, Zhi-Chun Huang, Peng Wang, Lei Ren,Yi Diao. Enhanced brain targeting of Temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. International Journal of Nanomedicine 2011:6 445–452.

53.      Wolfgang Mehnart and Karsten Mader, Adv. Drug. Deliv. Rev., 47, 165-196 (2001).

54.      Lee, W.A., Ennis, R.D., Longenecker, J.P., Bengtsson, P. (1994). The bioavailability of intranasal salmon calcitonin in healthy volunteers with and without permeation en-hancer. Pharm Res.

55.      Vila, A., Gill, H., McCallion, O., Alonso, M.J. (2004). Trans-port of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. J Control Release 98(2): 231-244.

56.      Vila, A., Gill, H., McCallion, O., Alonso, M.J. (2004). Trans-port of PLA-PEG particles across the nasal mucosa: effect of particle size and PEG coating density. J Control Release 98(2): 231-244.

57.      Videira, M.A., Botelho, M.F., Santos, A.C., Gouveia, L.F., de Lima, J.J., Almeida, A.J. (2002). Lymphatic uptake of pulmonary delivered solid lipid nanoparticles. J Drug Target 10(8): 607-613.

58.      Friedrich, I., Reichl, S., Müller-Goymann, C.C. (2005). Drug release and permeation studies of nanosuspensions based on solidified reverse micellar solutions (SRMS) Int J Pharm 305(1-2): 167–75.

59.      Dingler, A., Blum, R.P., Niehus, H., Müller, R.H., Gohla, S. (1999). Solid lipid nanoparticles (SLN™/Lipopearls™)– a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products. J Microencapsul. 16(6): 751-767.

60.      Wissing, S.A., Muller, RH. (2003). Cosmetic applications for solid lipid nanoparticles (SLN) Int J Pharm 254(1): 65-68.

61.      Chen, H., Chang, X., Du, D., Liu, W., Liu, J., Weng, T., Yang, Y., Xu, H., Yang, X. (2006). Podophyllotoxin-loaded solid lipid nanoparticles for epidermal targeting. J Control Release 110(2): 296-306.

62.      ShuyuXie, Luyan Zhu, Zhao Dong and Yan Wang, Colloids and Surfaces, Bio interfaces, 2011, 382-387.

 

 

 

 

 

 

 

 

 

Received on 16.04.2019           Modified on 21.05.2019

Accepted on 18.06.2019         © RJPT All right reserved

Research J. Pharm. and Tech. 2019; 12(11):5605-5613.

DOI: 10.5958/0974-360X.2019.00971.5