Drug-loaded Solid Lipid Nanoparticles Research Articles

Solid lipid nanoparticles self-assembled from spray dried microparticles.

We report the self-assembly of drug-loaded solid lipid nanoparticles (SLNs) from spray dried microparticles comprising poly(vinylpyrrolidone) (PVP) loaded with glyceryl tristearate (GTS) and either indomethacin (IMC) or 5-fluorouracil (5-FU). When the spray dried microparticles are added to water, the PVP matrix dissolves and the GTS and drug self-assemble into SLNs. The SLNs provide a non-toxic delivery platform for both hydrophobic (IMC) and hydrophilic (5-FU) drugs. They show extended release profiles over more than 24 h, and in permeation studies the drug cargo is seen to accumulate inside cancer cells. This overcomes major issues with achieving local intestinal delivery of these active ingredients, in that IMC permeates well and thus will enter the systemic circulation and potentially lead to side effects, while 5-FU remains in the lumen of the small intestine and will be secreted without having any therapeutic benefit. The SLN formulations are as effective as the pure drugs in terms of their ability to induce cell death. Our approach represents a new and simple route to the fabrication of SLNs: by assembling these from spray-dried microparticles on demand, we can circumvent the low storage stability which plagues SLN formulations.

On the Structure of Solid Lipid Nanoparticles.

Solid lipid nanoparticles (SLNs) have a crystalline lipid core which is stabilized by interfacial surfactants. SLNs are considered favorable candidates for drug delivery vehicles since their ability to store and release organic molecules can be tailored through the identity of the lipids and surfactants used. When stored, polymorphic transitions in the core of drug-loaded SLNs lead to the premature release of drug molecules. Significant experimental studies have been conducted with the aim of investigating the physicochemical properties of SLNs, however, no molecular scale investigations have been reported on the behaviors that drive SLN formation and their polymorphic transitions. A combination of small angle neutron scattering and all-atom molecular dynamics simulations is therefore used to yield a detailed atomistic description of the internal structure of an SLN comprising triglyceride, tripalmitin, and the nonionic surfactant, Brij O10 (C18:1 E10 ). The molecular scale mechanisms by which the surfactants stabilize the crystalline structure of the SLN lipid core are uncovered. By comparing these results to simulated liquid and solid aggregates of tripalmitin lipids, how the morphology of the lipids vary between these systems is demonstrated providing further insight into the mechanisms that control drug encapsulation and release from SLNs.

DEVELOPMENT AND EVALUATION OF TIZANIDINE HYDROCHLORIDE LOADED SOLID LIPID NANOPARTICLES

Objectives: The primary objective of the present study is to develop and evaluate tizanidine hydrochloride (TZ) solid lipid nanoparticles (SLNs) using solid lipids/triglycerides.
 Methods: TZ SLNs were prepared by hot homogenization followed by ultrasonication technique. The prepared SLNs were characterized for drug content, entrapment and loading efficiency, particle size, zeta potential, polydispersity index (PDI), and in intro release kinetics.
 Results: TZ SLNs were prepared. The particle size ranged from 49.7 to 523.7 nm. PDI of all formulations was good within the range of 0.189–0.487. The zeta potential of blank SLNs was −15.2 mV whereas drug-loaded SLNs showed zeta potential from −8.85 mV to −42.0 mV. Entrapment efficiency observed was in the range of 34.5–75.0%. The cumulative percentage release of TZ from different TZ nanoparticles varied from 35.28% to 83.98% depending on the drug-lipid ratio and the type of lipid and surfactant used. The release kinetic studies of optimized formulation showed that the release was first order and the release mechanism was non-Fickian type.
 Conclusion: The prepared SLNs were able to sustain the drug release for 24 h, thus reducing dosing frequency and occurrence of side effects, thereby increasing the effectiveness of the drug.

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.

Formulation, optimization, and characterization of rifampicin-loaded solid lipid nanoparticles for the treatment of tuberculosis

Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box–Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456 ± 11 nm, %EE of 84.12 ± 2.78%, and %DL of 15.68 ± 1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6 months does not revealed any significant change in characteristics of developed RIF-SLNs.

Encapsulation of ritonavir in solid lipid nanoparticles: in-vitro anti-HIV-1 activity using lentiviral particles.

In this study, ritonavir was entrapped into solid lipid nanoparticles (SLNs) employing two production methods. The prepared SLNs were characterized and antiretroviral activity was investigated for more efficient formulation. Ritonavir-loaded SLNs were produced by solvent emulsification evaporation (SE) and double emulsion methods (DE), and the effects of Tween80 and poloxamer188 as external phase surfactant were compared. Prepared SLNs were characterized in terms of size, surface charge, entrapment efficiency (EE), release profile and thermal behaviour. Moreover, the activity of drug-loaded SLNs was investigated on the lentiviral-based pseudo-HIV-1 particles. The average size of negatively charged SLNs was 170-250 nm with polydispersity index (PDI) of 0.2. The most EE% was about 53.2% achieved by DE method in the presence of poloxamer188. It was found that addition of poloxamer188 in the process led to increased entrapment efficiency and particle size. The in-vitro antiviral experiment showed ritonavir SLNs can actively maintain inhibition of virus production as well as free drug. In this study, we showed the SLNs not only can encapsulate ritonavir efficiently but also can maintain its antiviral activity and modulate drug release as promising nanocarrier.

Microwave-assisted microemulsion technique for production of miconazole nitrate- and econazole nitrate-loaded solid lipid nanoparticles

The microwave-assisted production of solid lipid nanoparticles (SLNs) is a novel technique reported recently by our group. The small particle size, solid nature and use of physiologically well-tolerated lipid materials make SLNs an interesting and potentially efficacious drug carrier. The main purpose of this research work was to investigate the suitability of microwave-assisted microemulsion technique to encapsulate selected ionic drug substances such as miconazole nitrate and econazole nitrate.The microwave-produced SLNs had a small size (250–300nm), low polydispersity (<0.20), high encapsulation efficiency (72–87%) and loading capacity (3.6–4.3%). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies suggested reduced crystallinity of stearic acid in SLNs. The release studies demonstrated a slow, sustained but incomplete release of drugs (<60% after 24h) from microwave-produced SLNs. Data fitting of drug release data revealed that the release of both drugs from microwave-produced SLNs was governed by non-Fickian diffusion indicating that drug release was both diffusion- and dissolution- controlled.Anti-fungal efficacy of drug-loaded SLNs was evaluated on C. albicans. The cell viability studies showed that cytotoxicity of SLNs was concentration-dependent. These encouraging results suggest that the microwave-assisted procedure is suitable for encapsulation of ionic drugs and that microwave-produced SLNs can act as potential carriers of antifungal drugs.

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.

Development and in vivo evaluation of an innovative “Hydrochlorothiazide-in Cyclodextrins-in Solid Lipid Nanoparticles” formulation with sustained release and enhanced oral bioavailability for potential hypertension treatment in pediatrics

An innovative pediatric oral formulation of hydrochlorothiazide (HCT) (2mg/mL), endowed with improved bioavailability and sustained release properties and suitable for the hypertension treatment in pediatric patients, was developed by combining the drug-cyclodextrin complexation and the incorporation of the complex into Solid Lipid Nanoparticles (SLN). Precirol®ATO5-based SLN, with two different surfactants (Pluronic®F68 and Tween®80) loaded with the drug as such or as binary system with hydroxypropyl-beta-cyclodextrin (HPβCd) and sulfobutyl-ether-beta-cyclodextrin (SBEβCd) both as physical mixture (P.M.) or coground product (GR), were prepared using the hot high-shear homogenization followed by ultrasonication method. Loading of the drug:HPβCd both as P.M. and GR gave rise to nanoparticle formation, differently from the HCT:SBEβCd ones, with an entrapment efficiency of about 65%. Such SLN formulations showed an improvement of the drug release rate compared both to the drug suspension and to the free drug-loaded SLN. In all cases the SLN containing the GR systems exhibited better performances than the corresponding with P.M. However, the presence of Tween®80 gave rise to the complete drug release after only 150min, without providing a sustained release, whereas Pluronic®F68-based SLN containing GR were able to assure a sustained release over the time achieving more than 75% drug released at the end of the test, maintaining a constant 1.8-fold increase respect to simple drug suspension. Pluronic®F68-based SLN showed a pharmaceutically acceptable stability up to three months. In vivo studies highlighted the effectiveness of such formulations, enabling a concomitant increased diuretic effect and a sustained drug release and, consequently, enhanced HCT oral bioavailability.

Microwave-assisted formulation of solid lipid nanoparticles loaded with non-steroidal anti-inflammatory drugs

Stearic acid-based solid lipid nanoparticles (SLNs) were prepared using the microwave assisted one-pot microemulsions procedure pioneered by our group. In this study, non-steroidal anti-inflammatory drugs (NSAIDs) including indomethacin, ketoprofen and nimesulide were selected as ideal “test” drugs, based on their poor water solubility. The model drugs were incorporated within the SLNs by the microwave-assisted procedure at the time of SLN production. The microwave-produced drug-loaded SLNs were evaluated in terms of their physicochemical characteristics, drug release behavior and their uptake into against A549 cell line (human lung epithelial cells). The microwave-produced drug-loaded SLNs had a small particle size distribution, negative zeta potential and high encapsulation efficiency. The drug release studies were consistent with a core-shell structure of SLNs (probably a drug-loaded shell) which results in biphasic drug release from the SLNs. The drug release kinetics suggested a good fit of the release data to the Makoid-Banakar model and was governed by Fickian diffusion. The drug-loaded SLNs showed concentration-dependent cytotoxicity and reduced IL-6 and IL-8 secretion in lipopolysaccharide-induced cells. All of the above findings suggest that the microwave-produced SLNs could be promising drug carriers of NSAIDs and will further facilitate their development for topical, oral and/or nasal administration.

Encapsulation of clotrimazole into solid lipid nanoparticles by microwave-assisted microemulsion technique

Recently, we reported a novel microwave-assisted one-pot microemulsion procedure for the production of solid lipid nanoparticles (SLNs). In the current study, the suitability of the microwave-assisted procedure in encapsulation of clotrimazole was investigated. Clotrimazole, a synthetic, imidazole-type anti-fungal drug, was used as lipophilic model drug. The particle sizes of microwave-produced stearic acid-based clotrimazole-loaded SLNs were within the nanometer size range with zeta potential values high enough to predict good physical stability. High encapsulation efficiency and loading capacity demonstrated the high encapsulation capability of microwave-produced SLNs. Physicochemical characterization of SLNs and bulk stearic acid, performed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD), indicated decreased crystallinity of stearic acid, a factor that influences incorporation and release of drug. The release studies demonstrated a slow and sustained but incomplete release of drugs (<50% after 12h and <70% after 24h). The release of clotrimazole was found to be governed by both diffusion and swelling, i.e. anomalous or non-Fickian diffusion. The release data, however, fitted more appropriately to the Weibull model. The clotrimazole-loaded SLNs were found to be non-toxic, investigated by cell viability assays using human epithelial A549 and mouse epithelial 3T3-L1 cell lines. The cytotoxic concentration (CC50) value was greater than 100μg/mL. Internalization of SLNs into A549 cells by endocytosis was demonstrated by confocal imaging. The antifungal efficacy of drug-loaded SLNs was evaluated on Candida albicans. These encouraging results suggest that microwave-produced SLNs can be considered as efficient carriers for clotrimazole and will further assist their development for administration via different routes.

Evaluation of the Hydatid Cyst Membrane Permeability of Albendazole and Albendazole Sulfoxide-Loaded Solid Lipid Nanoparticles

Background: Albendazole (ABZ) and albendazole sulfoxide (ABZSO) have a basic role in the treatment of hydatid cysts. However, their poor solubility and limited intestinal permeability are the main problems in their formulation. Objectives: The preparation and characterization of ABZ and ABZSO-loaded solid lipid nanoparticles (SLNs) to increase the hydatid cyst membrane permeation by loading into SLNs. Materials and Methods: First, ABZ and ABZSO-loaded SLNs were prepared by micro emulsification and high shear homogenization. Physicochemical characterization of the formulations for particle size, polydispersity index, drug entrapment efficiency (EE) and drug loading (DL), zeta potential, particle shape, drug stability, and in vitro drug release studies were evaluated. Next, the permeability of conventional and prepared formulations on hydatid cysts was evaluated by quantifying the drug concentrations in cyst fluid using high-performance liquid chromatography (HPLC). Results: The prepared formulations showed particle sizes < 180 nm, polydispersity index values around 0.08 with narrow size distributions, a high EE of (91%) for ABZ-SLN and (94%) for ABZSO-SLN, and ideal stabilities with regard to their largely negative zeta potentials. The in vitro drug release of free drugs exhibited very fast release in the initial time, but displayed a biphasic pattern for drug-loaded SLNs. Greater permeability was achieved using the SLN preparations. Conclusions: ABZ and ABZSO achieved good physicochemical characterizations, controlled release, higher permeability and efficacy by loading into SLNs, and are promising for the treatment of this disease.

Evaluation of the Hydatid Cyst Membrane Permeability of Albendazole and Albendazole Sulfoxide-Loaded Solid Lipid Nanoparticles

Background: Albendazole (ABZ) and albendazole sulfoxide (ABZSO) have a basic role in the treatment of hydatid cysts. However, their poor solubility and limited intestinal permeability are the main problems in their formulation. Objectives: The preparation and characterization of ABZ and ABZSO-loaded solid lipid nanoparticles (SLNs) to increase the hydatid cyst membrane permeation by loading into SLNs. Materials and Methods: First, ABZ and ABZSO-loaded SLNs were prepared by micro emulsification and high shear homogenization. Physicochemical characterization of the formulations for particle size, polydispersity index, drug entrapment efficiency (EE) and drug loading (DL), zeta potential, particle shape, drug stability, and in vitro drug release studies were evaluated. Next, the permeability of conventional and prepared formulations on hydatid cysts was evaluated by quantifying the drug concentrations in cyst fluid using high-performance liquid chromatography (HPLC). Results: The prepared formulations showed particle sizes < 180 nm, polydispersity index values around 0.08 with narrow size distributions, a high EE of (91%) for ABZ-SLN and (94%) for ABZSO-SLN, and ideal stabilities with regard to their largely negative zeta potentials. The in vitro drug release of free drugs exhibited very fast release in the initial time, but displayed a biphasic pattern for drug-loaded SLNs. Greater permeability was achieved using the SLN preparations. Conclusions: ABZ and ABZSO achieved good physicochemical characterizations, controlled release, higher permeability and efficacy by loading into SLNs, and are promising for the treatment of this disease.

Surfactant effect on the physicochemical characteristics of γ-oryanol-containing solid lipid nanoparticles

Abstract Surfactants employed in production of solid lipid nanoparticles (SLNs) play a major role on physical stability of nanoparticles, and the extent of drug dissolution and permeability into cells. In this study, cationic (cetyl pyridinium chloride), anionic (sodium dodecyl sulfate) and non-ionic (Tween 80) surfactants, as well as its combinations, were employed to formulate compritol based SLNs using γ-oryzanol as a model drug. The physicochemical properties of drug-loaded SLNs are influenced by the surfactant composition systems. Surfactant blend systems gave SLNs with superior stability compared with single surfactant systems due to enhanced incorporation of the drug within the solid lipid matrix. This may be due to synergic effects arising from electrostatic repulsion of the surfactant charges (ionic), the steric hindrance of surfactant structure (non-ionic), and ion-pairing effects between cationic and anionic ones. The cytotoxicity results demonstrated that positively charged SLNs can be uptaken into cells to a high extent. Nevertheless, the mixed surfactant systems (cationic/non-ionic and cationic/anionic/non-ionic), have remarkable advantages providing SLNs with high cell internalization capability, however, low cytotoxicity. This systematic investigation may give an insight into the practical integration of multi-surfactant systems to achieve non-toxic and highly effective drug delivery systems.

Tamoxifen-loaded solid lipid nanoparticles-induced apoptosis in breast cancer cell lines

An in vitro study was conducted to determine the apoptosis induced by tamoxifen (TAM) and TAM-loaded solid lipid nanoparticles (SLNs) in breast cancer cell lines, MCF-7 and MDA-MB231 cells. The effect of free drug and drug-loaded SLN on the cell lines was characterised by cell morphology and cell cycle distribution using phase contrast microscopy, nuclear morphology and flow cytometry, respectively. The results showed that TAM-loaded SLNs have an equally efficient cytotoxic activity against MCF-7 and MDA-MB231 cells, compared to free TAM, and the half maximal inhibitory concentration (IC50) of TAM-loaded SLNs was generally lower than that of free TAM. In the presence of TAM and TAM-loaded SLN, the viability of the both cells diminishes and the cancer cells lose their normal morphological characteristics, detaches, aggregates and later develops apoptotic bodies. Flow cytometry analysis showed that TAM-loaded SLN like the free TAM caused a dose- and time-dependent apoptosis without cell cycle arrest of human breast cancer cells. Therefore, TAM-loaded SLN has great potential in human medicine for the treatment of breast cancers.

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.

Dual drugs (microRNA-34a and paclitaxel)-loaded functional solid lipid nanoparticles for synergistic cancer cell suppression.

A co-delivery system that can transport cancer related microRNAs and chemotherapeutics to their distinct targets in the tumors is an attractive strategy to eliminate tumor relapse in lung cancer therapy. In this study, we developed a dual-drug delivery system for an endogenous microRNA (miR-34a) and paclitaxel (PTX) for synergistic cancer therapy. PTX (a meiotic inhibitor) and miR-34a were loaded into cationic solid lipid nanoparticles (miSLNs-34a/PTX) which were used to treat murine B16F10-CD44(+) melanoma metastasized to the lungs of mice. This nanoparticle system demonstrated good protection for miR-34a and PTX from degradation in the serum, and had an average size of approximately 220 nm by photon correlation spectroscopy (PCS). In vitro, the parallel activity of PTX and miR-34a show synergistic anticancer efficacy. In vivo, miSLNs-34a/PTX showed passive targetability to the tumor-bearing lung tissues, and was demonstrated to be much more potent in inhibition of B16F10-bearing tumor growth and elimination of cancer cell populations in the lung than single drug-loaded solid lipid nanoparticles. It has been shown that such co-delivery of miR-34a and PTX is promising for enhanced cancer therapy to reduce tumor relapse.

Solid lipid nanoparticles loaded with fluorescent-labelled Cyclosporine A: anti-inflammatory activity in vitro.

FMOC-isocyclosporine A, a fluorescent labeled cyclosporine A, was encapsulated in solid lipid nanoparticles (SLN) prepared by the coacervation technique, and its anti-inflammatory activity was evaluated. The anti-inflammatory activity of the fluorescent labelled molecule, measured as inhibition of TNF-α secretion, is similar to the native one. SLN were compared to commercial formulations, through measurement of cytokine release and drug uptake in rat peripheral blood mononuclear cells. Drug-loaded SLN inhibit TNF-α secretion in a lower extent than commercial formulations, probably due to a lower uptake by the cells, but the increase of IL-10 secretion caused by the lipid matrix itself makes this formulation interesting for its anti-inflammatory activity.

In vivo pharmacokinetics and biodistribution of resveratrol-loaded solid lipid nanoparticles for brain delivery

Resveratrol is a potent anticancer. However, because of its low half-life (<0.25h) the molecule is difficult to achieve the therapeutic concentration at the site of action. The aim of this work was to check the brain targeting ability of glyceryl behenate-based solid lipid nanoparticles (SLN) for resveratrol. SLN were prepared by solvent evaporation technique employing high speed homogenization followed by ultrasonication. SLN were designed at varying drug–lipid ratios (1:5, 1:9, 1:10, 1:11, 1:12 and 1:15) using Tween 80 or a combination of Tween 80 and polyvinyl alcohol (PVA) as surfactants. The mean particle size and zeta potential of the optimized formulation (drug–lipid ratio of 1:10) were 248.30±3.80nm and −25.49±0.49mV, respectively. The particle size and the encapsulation efficiency (EE) increased when varying the drug–lipid ratio from 1:5 to 1:15. Scanning electron microscopic (SEM) analysis showed that SLN were spherical in shape and had a smooth surface. The X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses revealed that the matrix of drug-loaded SLN was in disordered crystalline phase. The in vitro release study in phosphate buffer pH 7.4 followed a sustained release pattern. The drug release data was found to fit best into Higuchi kinetic model suggesting the diffusion controlled mechanism of drug release. The cytotoxicity assay (MAT) showed that SLN were equally effective (P<0.5) as free resveratrol, as an anti-tumor agent. The in vivo biodistribution study using Wistar rats demonstrated that SLN could significantly (P<0.001) increase the brain concentration of resveratrol (17.28±0.6344μg/g) as compared to free resveratrol (3.45±0.3961μg/g). The results showed that our resveratrol-loaded SLN serve as promising therapeutic systems to treat neoplastic diseases located in the brain tissue.

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.