Size Of Solid Lipid Nanoparticles Research Articles

Drug-Lipid-Surfactant Miscibility for the Development of Solid Lipid Nanoparticles.

This research aimed to study the correlation between miscibility of flutamide (FLT), lipids and surfactant on the particle size of solid lipid nanoparticles (SLNs). Physical mixtures (PMs) of lipids-glyceryl monooleate (GMO), Precirol® (glyceryl palmitostearate, PRE), glyceryl monostearate (GMS), and Compritol® (glyceryl dibehenate, COM) were prepared with surfactant-Gelucire® (stearoyl polyoxyl-32 glycerides, GEL) 50/13 and 44/14. PMs were prepared in 5:2 w/w ratio (lipid:surfactant) and 2:1 w/w (Flutamide (FLT):lipids/GEL 50/13) by co-melting. Miscibility of PMs was investigated using modulated differential scanning calorimetry (MDSC). SLNs with and without drug were prepared using GEL 50/13 by the ultra-sonication method and particle size analysis was conducted. PMs of GMO, GMS, and PRE with both surfactants showed a decrease in the melting temperature, no change in melting and crystallization peak was observed with COM-GELs, indicating immiscibility. Similarly, MDSC data suggests good miscibility of FLT in GMO, GMS, and GEL 50/13 but not in PRE and COM. The particle size of drug-loaded SLNs prepared from GMO and GMS with GEL 50/13 was found to be 70.2 ± 5.4 and 92.6 ± 8.5 compared to > 200-nm particles obtained from PRE and COM. On lyophilization, an increase in particles size was observed with COM only. The particle size of SLNs with PRE and COM was prominently increased during stability studies indicating SLNs prepared with GMO and GMS are more stable due to miscibility and ability to reduce the crystallinity of FLT. The results established a good correlation between drug, lipids, and surfactants miscibility to the obtained particle size of SLNs before and after lyophilization. Graphical Abstract ᅟ.

Novel Solid Lipid Nanocarrier of Glibenclamide: A Factorial Design Approach with Response Surface Methodology.

In the present investigation, a factorial design approach attempt was applied to develop the Solid Lipid Nanoparticles (SLN) of Glibenclamide (GLB) a poorly water-soluble drug (BCS -II) used in the treatment of type 2 diabetes. Prime objectives of this experiment are to optimize the SLN formulation of Glibenclamide and improve the therapeutic effectiveness of the developed formulation. Glibenclamide loaded SLNs (GLB-SLN) were fabricated by High speed homogenization technique. A 32-factorial design approach has been employed to assess the influence of two independent variables, namely amount of Poloxamer 188 and Glyceryl Monostearate on entrapment efficiency (% EE) (Y1), Particle Size (nm) (Y2), % drug release at 8hr Q8 (Y3) and 24 hr Q24 (Y4) of prepared SLNs. Differential scanning calorimetry analysis revealed the compatibility of the drug into lipid matrix with a surfactant, while Transmission electron and Scanning electron microscopy studies indicated the size and shape of SLN. The entrapment efficiency, particle size, Q8 and Q24 of the optimized SLNs were 88.93%, 125 nm, 31.12±0.951% and 86.07±1.291% respectively. Optimized GLB-SLN formula was derived from an overlay plot. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. In vivo testing of the GLB-SLN in diabetic albino rats demonstrated the significant antidiabetic effect of GLB-SLN. The hypoglycemic effect obtained by GLB-SLN remained significantly higher than that given by drug alone and marketed formulation, further confirming the higher therapeutic effectiveness of the GLB-SLN formulation. Our findings suggested the feasibility of the investigated system for oral administration of Glibenclamide.

Piroxicam loaded solid lipid nanoparticles for topical delivery: Preparation, characterization and in vitro permeation assessment

During the recent years, there has been growing attention to the development of topical delivery systems to facilitate drug permeation through the skin. The drugs commonly used are those with debatable oral administration. Piroxicam is a valuable anti-inflammatory, antipyretic and analgesic drug, however, its long-term oral administration is limited due to the various gastrointestinal side effects. The main purpose of this study was to prepare and assess a topical formulation of piroxicam, based on solid lipid nanoparticles (SLNs), to improve its percutaneous permeation rate. Topical Nanolipidic gel of piroxicam was formulated and its pharmaceutical characteristics were evaluated. Piroxicam loaded SLNs were formulated by solvent emulsification/evaporation method. Particle size assessment, entrapment efficiency assessment, in vitro release study and skin permeation of the piroxicam were carried out to characterize the SLNs. These SLNs were then formulated in gel as a topical delivery system to assess percutaneous permeation of piroxicam. The SLNs were prepared in different size ranges from 100 to 300 nm and drug release behavior from two different nano-sized SLN suspensions was evaluated. Piroxicam nanolipidic gel exhibited increased skin permeation of the drug over commercial piroxicam gel formulation and also mean particle size of formulated SLNs had a significant effect on permeation rates.

Observation of chitosan coated lipid nanoparticles with different lipid compositions under simulated in vitro digestion system

The effects of lipid composition and chitosan coating on lipid digestion ability were investigated using a simulated in vitro digestion system, including oral, gastric, and small intestine stages. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were prepared with only palm oil and the mixture of palm oil and medium-chain triglyceride (MCT) oil, respectively. Chitosan-coated SLNs (CS-SLNs) and NLCs (CS-NLCs) were prepared with a drop-wise method. CS-NLCs were more completely digested than the NLCs, while the NLCs showed higher free fatty acid release than SLNs. Chitosan coating increased the particle size of both SLNs and NLCs from 100.0 to 104.9 nm to 130.0 and 146.5 nm, respectively. Chitosan coating also increased the initial digestion rate of NLCs by modulating lipid droplet aggregation. But, chitosan coating showed little impact on the digestion of SLNs because SLNs did not strongly impact the lipid droplet aggregation state. These results have important implications for the fabrication of functional foods and beverages to achieve control of lipid digestion in the gastrointestinal tract.

Controlled SLN Delivery by Thermoresponsive In-situ Forming Erodible Gels; A Whole-body and Organ Imaging Study.

Nanoparticles (NPs) suffer from rapid clearance from body and require frequent dosing if long treatment is required. In order to solve this problem for solid lipid nanoparticles (SLN) and prolong their action, SLNs were incorporated into thermo-responsive Poloxamer sol-gels and their fate was investigated invivo and in-vitro using a near infrared lipophilic fluorescent dye; dialkylcarbocyanin [1]. Leakage test, release of intact SLNs from sol-gel and SLN size and zeta potential were investigated. Biodistribution of DiR formulations (solution, free SLN and SLN-Gel) was investigated by whole-body and ex-vivo organ imaging after intraperitoneal injection in mice. SLN showed particle size of about 165 nm and a negative zeta potential of about -36 mV. Leakage studies indicated that fluorescent probe does not release from SLNs. Imaging results revealed a steady profile for SLN-Gel over time, while the fluorescence intensity of solution and free SLN showed a burst followed by rapid clearance. Results also showed that SLN release occurs after gel erosion and follows a zero order profile. Our results indicate that NP-incorporated gel can be used to control the release of SLNs from application site and prolong their action in a sustained manner.

Development, In Vitro Characterization, Antitumor and Aerosol Performance Evaluation of Respirable Prepared by Self-nanoemulsification Method.

Poor water solubility and low oral bioavailability limit the clinical application of Erlotinib as an anticancer. For this purpose, we encapsulated erlotinib in the solid lipid nanoparticles (SLN) and designed a spray-dried dry powder inhalable (DPI) formulation. Erlotinib-loaded SLNs were prepared using self-nanoemulsifying and characterized for physicochemical properties. Pulmonary deposition of spray-dried DPI formulation was performed using Next Generation Impactor. The particle size and zeta potential of Erlotinib-loaded SLNs were 300 to 800 nm and -18 to -32 mV, respectively. High drug entrapment efficiency in the narrow range of 80-85% was achieved. Cytotoxicity results indicated that cell growth inhibition of free drug and drug loaded nanoparticles is dose- and time-dependent. Inhalable dry powders prepared from drug-loaded SLNs were found to have a fine particle fraction in the range of 6.92±0.99 -11.24±2.4%, mean mass aerodynamic diameter in the range of 4.52±0.1 to 6.67±0.5 µm. The findings revealed that the proposed inhalable dry powder formulation loaded with erlotinib SLN has potential in lung cancer therapy through pulmonary route.

The effect of a lipid composition and a surfactant on the characteristics of the solid lipid microspheres and nanospheres (SLM and SLN)

Solid lipid microparticles (SLM) were produced by a two-step process that, firstly, involved the emulsification of the molten lipid phase in a heated aqueous phase and, secondly, the system cooling. Compritol 888 ATO and Precirol ATO 5, including their mixtures with Miglyol 812 or Witepsol H15 were used as lipid components (10–30% w/w). The average size of the SLM prepared with Compritol and Tween 80 as an emulsifier was 3–7μm and the influence of lipid concentration and thermal sterilization was not large. Dispersions of SLM with Precirol (10–20% w/w) gellified upon storage. SLM stabilized with another surfactant, Tego Care 450, were larger in size and measured 40μm on average. The use of the sonication step (5–15min) in hot formulations containing 5% w/w of Compritol resulted in the formation of the solid lipid nanoparticles (SLN) with average size 200–300nm. The smallest SLN size (below 100nm on average) was obtained in SLN that contained Tego Care and an antimicrobial agent Euxyl PE 9010; such combination evoked synergism between the surfactant and Euxyl components.

Effect of particle size on oral bioavailability of darunavir-loaded solid lipid nanoparticles

The present investigation aimed to study the effect of particle size of solid lipid nanoparticles (SLNs) on oral bioavailability of darunavir. High pressure homogenisation technique was used to prepare SLNs. Three different sized SLNs loaded with darunavir were developed with mean particle sizes of around 100 nm, 200 nm and 500 nm, respectively. The in vivo pharmacokinetics in rats showed a significant increase in oral bioavailability of darunavir from all the three formulations in comparison to plain drug suspension and reference tablet. The results revealed insignificant difference between SLNs of 100 and 200 nm and these had significantly higher bioavailability in comparison to SLNs of 500 nm. However, more number of homogenisation cycles is required for obtaining 100 nm and thus we selected 200 nm as an optimum size for oral bioavailability enhancement of darunavir. The optimised SLN formulation was stable for a period of 6 months at 25 ± 2 °C/60 ± 5% relative humidity (RH).

The Impact of Variables on Particle Size of Solid Lipid Nanoparticles and Nanostructured Lipid Carriers; A Comparative Literature Review.

During the past decade, pharmaceutical science has seen rapid growth in interest for nanoscale materials. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are popular research topics recently introduced as nano-scale drug carriers; they have shown numerous merits in drug delivery. Size is the most important index in a nanocarrier affecting its drug delivery efficiency. The influence of preparation conditions and type of lipidic components on the size of SLN and NLC in comparable states seems to be interesting for researchers who investigate these types of carriers. This review highlights the results of SLN and NLC particle size and size distribution comparisons.

Preparation and investigation of solid lipid nanoparticles for drug delivery

Solid lipid nanoparticles (SLN), a promising drug delivery vehicle, offer an alternative system to traditional colloidal carriers. In our study 12 new SLN formulations were fabricated via the “microemulsion (ME) method”, each leading to a different SLN size and composition. This method is a relatively easy technique and involves biocompatible conditions. Stearic acid has been used as lipid material of which the ratio is kept under 4% to prevent particle growth. Particle size and surface properties of the synthesized SLNs were controlled using various combinations of emulsifiers such as lithocholic acid, Pluronic F127, Tween 20, lecithin and butanol. Furthermore, the mean size of the particles was adjusted by changing the ME:water ratio in the dilution step which is independent from composition. It was found that most of the SLNs were in the colloidal size range (below 100nm) and spherical in shape, which provides high surface area to exploit, as an alternative adsorptive drug carrier system. Also, the surface charge density values of SLNs were calculated by considering size and zeta potential values which then helps in understanding the surface potential of particles. MB was chosen as a model molecule and entrapped on the surface of SLNs after the preparation, to determine the loading capacities and release efficiencies. As such, SLNs have been successfully produced which have controllable drug entrapment efficiency and release capacity according to the chosen combination of emulsifiers and dilution ratio. Thus, this study contributes to the improvement of alternative drug delivery systems with biocompatible and stable newly formulated SLNs.

Shea butter solid nanoparticles for curcumin encapsulation: Influence of nanoparticles size on drug loading

In the present work, shea butter solid lipid nanoparticles (SLN) were prepared by sonication using nonionic surfactants as stabilizers without organic solvent. The mixture design methodology enabled to control particles size from 50 nm to more than 1 μm according to the mixture composition. Then, curcumin, a natural polyphenol, has been encapsulated in nanoparticles with a wide range of diameters (50–230 nm) and the encapsulation efficiency has been related to the particles sizes. The bigger the nanoparticles, the lower the encapsulation efficiency. The lipid structure at non dispersed state and under SLN form has been studied by differential scanning calorimetry and X‐ray diffraction. From the obtained results, encapsulated curcumin did not affect the lipid properties at the SLN state unlike at non dispersed state. The localization of the curcumin in the outer shell of the lipid nanoparticles explained the evolution of the encapsulation efficiency according to the nanoparticles size.Practical applications: Solid lipid nanoparticles (SLN) can be used for the delivery of both hydrophobic and hydrophilic drugs. Preparing such nanovectors with natural, non‐expensive materials and easily available (i.e., shea butter) will promote their potential use in several applications like oral, parenteral, dermal or ocular delivery. Controlling the particles size from the formulation composition and also the drug loading from SLN properties is of main importance to optimize the use of SLN as colloidal carrier.Mixture design of experiments methodology allowed the control of shea butter solid lipid nanoparticles size upon system composition. The influence of SLN size on the encapsulation efficiency of curcumin was studied.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia

Context: Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia.Objective: The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia.Methods: Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively.Results: The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug.Conclusion: It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.

Assessment of lactoferrin-conjugated solid lipid nanoparticles for efficient targeting to the lung.

The aim of the present study was to develop a target oriented drug delivery system for the lungs. Lactoferrin (Lf)-coupled solid lipid nanoparticles (SLNs) bearing rifampicin was prepared by a solvent injection method. The prepared nanoparticles were characterized for shape, particle size, polydispersity and percentage drug entrapment. An optimized formulation was then studied for its in vivo performance in animals and to determine its targeting efficiency. It was observed that, upon coupling with Lf, the size of SLNs increased while the percent entrapment efficiency decreases. In in vitro release, determined by a dialysis technique, analysis showed that uncoupled SLNs exhibited higher drug release as compared to coupled SLNs. An in vivo biodistribution study shows 47.7 ±0.4 drug uptakes by the lungs, which was 3.05 times higher in comparison to uncoupled SLNs. These biodistribution studies are further supported by the fluorescence study that revealed enhanced uptake of Lf-coupled SLNs in the lung. From the presented results, it can be concluded that Lf-coupled SLNs enhanced drug uptake in the lung. Moreover, lactoferrin is an efficient molecule that can be used for targeting active agents directly to the lung.

Factorial Design and Development of Solid Lipid Nanoparticles (SLN) for Gene Delivery.

Several scientific hurdles still have to be overcome before gene therapy becomes a reality. One of them is the development of safe and efficient gene delivery system. Here, we have employed factorial design to optimize the production of solid lipid nanoparticles (SLN) for gene delivery. A 2 x 3 full-factorial experimental design was used for the optimization of SLNs formulations. The variables were defined by the components of the formulation: concentration of stearic acid, DOTAP, and Pluronic F68 at two levels (-1, 1) and 3 central points (0). Different SNL formulations were prepared by varying the amount of components and several properties were tested, including their capacity to accommodate DNA and protection against DNase degradation, colloidal stability, in vitro cytotoxicity, and transfection efficiency in prostate cancer cells. Finally, response Surface Methodology was used to select the most effective formulation for gene delivery to prostate cancer cells in vitro. In conclusion, this study revealed that stearic acid and Pluronic F68 were determinant to SLN size and stability, respectively, while small amounts of DOTAP are essential for a successful transfection.

Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model

The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized. In addition, the cytotoxicity and transport ability of SLNs were also studied in Caco-2 cell model. The mean particle size of drug-loaded SLNs was significantly affected by the process variables. The SLNs were prepared using glyceryl monosterate (1% polyvinyl alcohol (PVA) or 1.5% poloxamer 188 as surfactant) had a regular shape with a relatively lower mean particle size (324.2 and 224.9nm, respectively), higher encapsulation efficacy (55.7 and 42.4%, respectively) and sustained drug release over 12h. The crystalline form of drug had been partly changed and no physicochemical interaction had occurred between drug and carriers in SLNs. The cell viability was approximately 100% even at a high concentration of blank SLNs. There was no remarkable difference in drug permeation between drug-loaded SLNs and drug solution at 2h, while drug-loaded SLNs showed a significant decrease in drug permeation compared with the drug solution at 4h. The process variables of zanamivir-loaded SLNs were successfully optimized in this study. However, these SLNs significantly reduced the transport ability of zanamivir across Caco-2 cell monolayers. Further studies are needed to fully understand the real absorption mechanism of developed SLNs.

Recombinant Human Epidermal Growth Factor (rhEGF)-loaded Solid Lipid Nanoparticles: Fabrication and Their Skin Accumulation Properties for Topical rhEGF Delivery

For the present study, rhEGF was encapsulated into solid lipid nanoparticles (SLNs). The SLNs were prepared by the W1/O/W2 double emulsification method combined with the high pressure homogenization method and the physical properties such as particle size, zeta-potential and encapsulation efficiency were measured. The overall particle morphology of SLNs was investigated using a transmission electron microscopy (TEM). The percutaneous skin permeation and accumulation property of rhEGF was evaluated using Franz diffusion cell system along with confocal laser scanning microscopy (CLSM). The mean particle size of rhEGF-loaded SLNs was 104.00 ± 3.99 nm and the zeta-potential value was in the range of �36.99 ± 0.54 mV, providing a good colloidal stability. The TEM image revealed a spherical shape of SLNs about 100 nm and the encapsulation efficiency was 18.47 ± 0.22%. The skin accumulation of rhEGF was enhanced by SLNs. CLSM image analysis provided that the rhEGF rat skin accumulation is facilitated by an entry of SLNs through the pores of skin.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles

The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug. The effect of different formulation variables on the particle size, polydispersity index and drug encapsulation efficiency of SLNs and NLCs was evaluated and compared. SLNs and NLCs were physicochemically characterized and compared using Cryo-SEM, DSC and XRD. Furthermore, a drug release study of SLNs and NLCs was conducted. Finally, physicochemical stability (size, PI, ZP, EE) of the SLNs and NLCs was checked at 25 ± 2 °C and at 2–8 °C. Among the sucrose esters, D-1216 was found to be most suitable for both SLNs and NLCs. Formulation variables exhibited a significant impact on size, PI and EE of the nanoparticles. SLNs with ∼120 nm size, ∼0.23 PI, ∼I26I mV ZP, ∼87% EE and NLCs with ∼160 nm size, 0.15 PI, ∼I26I mV ZP, ∼88% EE were produced. Cryo-SEM revealed spherical particles with a smooth surface but did not exhibit any difference in surface morphology between SLNs and NLCs. DSC and XRD results demonstrated the disappearance of clotrimazole peak(s) in drug-loaded SLNs and NLCs. Faster drug release was observed from SLNs than NLCs. NLCs were found to be more stable than SLNs in terms of size, PI, EE and drug release. The results indicated that both SLNs and NLCs stabilized with sucrose ester D-1216 can be used as controlled release carriers although NLCs have an edge over SLNs.

Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199 nm, while the SLNs prepared with palmitic acid had particle size in the range of 126–160 nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations.

Preparation, in vitro evaluation and statistical optimization of carvedilol-loaded solid lipid nanoparticles for lymphatic absorption via oral administration

Carvedilol-loaded solid lipid nanoparticles (SLNs) were prepared using solubility parameter (δ) to select the lipid, and hot homogenization to fabricate SLNs. The effect of concentration of Compritol 888 ATO (COMP) and Poloxamer 188 (P-188) on the particle size of blank SLNs was studied using the design of experiments. Further narrow concentration range of COMP and P-188 was selected and carvedilol-loaded SLNs were prepared to obtain an optimized formulation which was lyophilized (L-SLNs), transformed into enteric compression-coated tablet and evaluated for drug release, X-ray diffraction and cellular uptake mechanism. COMP was chosen as lipid due to its least value of Δδ with carvedilol. The optimized formulation (7.5% COMP, 5.0% P-188 and 1.11% carvedilol) had 161 nm particle size and 94.8% entrapment efficiency. The enteric-coated carvedilol-loaded SLNs tablet protected carvedilol from acidic environment and similar prolonged release profiles were obtained from L-SLNs, core tablet and enteric-coated tablet. Absence of crystalline carvedilol XRD peak indicated the presence of amorphous carvedilol in SLNs. Higher carvedilol uptake from SLNs compared to drug solution in the Caco-2 cell line exhibited a potential prolonged drug release. Moreover, upon cellular uptake, SLNs could then enter the lymphatic system which will avoid first pass metabolism and hence higher oral bioavailability.

Modeling the effect of sonication parameters on size and dispersion temperature of solid lipid nanoparticles (SLNs) by response surface methodology (RSM)

The objective of this study was to evaluate the effect of sonication time and pulse frequency on average dispersion temperature (ART), particle size and zeta potential of solid lipid nanoparticles (SLNs). A two-factor, three-level response surface methodology (RSM) was used to optimize sonication time between 5 and 15 min and pulse frequency from 30 to 90%. SLNs made from stearyl alcohol (SA) and cetyl trimethylammonium bromide (CTAB) blend at 1:3 ratio were prepared by applying high-shear homogenization and sonication. Pulse frequency and time were found to have a significant effect on particle size and ART. The effect of sonication parameters on zeta potential, however, was insignificant. The optimal sonication parameters for preparing 100 nm SLNs made from a SA/CTAB blend was 60% pulse frequency at 40% power for 10 min. Optimized sonication parameters were then used to investigate the effect of lipid type on SLN size and zeta potential. The mean particle sizes of SLNs made with SA, cetyl palmitate, Precirol®, Dynasan118® and Compritol® were 98, 190, 350, 350 and 280 nm, respectively. In conclusion, pulse frequency and time were found to be critical for obtaining SLNs with desirable size, whereas the stability of the SLNs was dependent on their lipid content.