Solid Lipid Nanoparticles Formulations Research Articles

Chronic administration of cryptolepine nanoparticle formulation alleviates seizures in a neurocysticercosis model

Worldwide, neurocysticercosis remains an important cause of acquired epilepsy. We therefore seek to investigate the effectiveness of the nanoparticle formulation of cryptolepine in alleviating seizures in a neurocysticercosis model.A solid-lipid nanoparticle formulation of extracted cryptolepine was prepared. The parasites were maintained in T. crassiceps metacestode (ORF strain) - infected female BALB/c mice. Cryp (5 ​mg/kg), SLN-CRYP (5 ​mg/kg), ABZ (50 ​mg/kg) DXM (0.5 ​mg/kg), and PHE (30 ​mg/kg).were assessed for in vitro cysticidal, in vivo cysticidal and/or antiseizure activity in 70 mice that had developed seizures from infection with T. crassiceps. General pathologic processes were studied in the host tissue and inflammatory mediators were quantified from isolated mice brains.All treatments (CRYP, SLN-CRYP and ABZ) caused significantly reduced viability of T. crassiceps cysts. Treatment with SLN-CRYP significantly shrunk cysticerci and resolved ventricular expansion and deviation similar to albendazole on examination of encephala. SLN-CRYP inhibited hyperemia but was more effective against microgliosis, calcification, edema and meningitis. Mean seizure score was significantly reduced in models administered with SLN-CRYP (p ​< ​0.0001); as were frequency (p ​< ​0.0001) and duration (p ​< ​0.0001) of seizures. SLN-CRYP significantly reduced brain homogenate levels of IL-10 (p ​= ​0.0016) and IFN-γ (p ​< ​0.0001).Our study shows that the chronic administration of the nanoparticle formulation of cryptolepine is effective in alleviating seizures associated with neurocysticercosis in a mouse model.

Preparation of cetyl palmitate-based PEGylated solid lipid nanoparticles by microfluidic technique

In recent years, several studies have shown that the use of solid lipid nanoparticles (SLN) as a colloidal drug delivery system was more advantageous than lipid emulsions, liposomes and polymeric nanoparticles. SLNs have numerous advantages of different nanosystems and rule out many of their drawbacks. Despite the numerous advantages of SLNs, translation from the preclinical formulation to the industrial scale-up is limited. In order to provide a reproducible and reliable method of producing nanoparticles, and thus, obtain an industrial scale-up, several methods of synthesis of nanoparticles by microfluidic have been developed. Microfluidic technique allows a good control and a continuous online synthesis of nanosystems compared to synthesis in bulk, leading to a narrow size distribution, high batch-to-batch reproducibility, as well as to the industrial scale-up feasibility. This work described the optimization process to produce SLNs by microfluidics. The SLNs produced by microfluidics were characterized by complementary optical and morphological techniques and compared with those produced by bulk method. SLNs were loaded with paclitaxel and sorafenib, used as model drugs. The anti-cancer efficiency of the SLNs formulation was estimated with 2D and 3D tumour models of two different cell lines, and the cellular uptake was also studied with fluorescence-assisted measurements.

Development of Candesartan Loaded Solid Lipid Nanoparticles by Box-Behnken Design

The primary motive behind this the present investigation was to develop and optimize the solid lipid nanoparticles formulation of candesartan to enhance solubility and dissolution rate. The prepared SLNs composed of precirol, poloxamer 188, soy lecithin, tween 80, were fabricated employing hot emulsification/ ultrasonication technique. Box-Behnken design was employed for 17 formulation batches in which 3 factors namely lipid, surfactant, and co-surfactant (precirol, poloxamer 188 and soy lecithin) tween 80 weretested at 3 levels of their concentration, i.e., low, medium and high. The effect of different levels of factors was evaluated for the particle size, entrapment efficiency and % cumulative drug release. Kinetic model fitting for candesartan solid lipid nanoparticles (SLN) formulation was done to interpret the release rate from the SLN. Optimized formulation was subjected for fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and stability studies. The mean particle size, PDI, zeta potential, entrapment efficiency, content uniformity and in-vitro drug release of optimized candesartan-loaded SLNs (CD10) were found to be 135.38 ± 3.41 nm, 0.125 ± 0.04, -18.16 ± 2.89 mV, 86.4 ± 2.35%, 99.78 ± 2.54% and 98.91 ± 0.85% respectively. The release kinetics suggested that drug release followed zero-order and release was anomalous non-fickian diffusion super case II transport. FTIR studies revealed no incompatibility between drug and excipients, SEM images exhibited nanoparticles to be more porous and in a spherical shape. Stability studies indicated good stability of the formulation. The proposed way of SLN preparation could be considered a proper method for producing a candesartan-loaded colloidal carrier system.

Design and Optimization of Itraconazole Loaded SLN for Intranasal Administration Using Central Composite Design

Introduction: Solid Lipid nanoparticles (SLN) are comprising of a solid lipid core with a mean diameter between 50 and 1000 nm. SLN is an advanced carrier system to traditional colloidal carriers such as emulsion, liposomes, and polymeric microparticles. Objective: The objective of this study was to formulate SLN of Itraconazole (ITZ) for intranasal administration. Methods: ITZ-loaded SLN were prepared by high pressure homogenization technique using the Central Composite Design (CCD). The concentration of surfactant (X1) and drug to lipid ratio (X2) was considered as independent variables, whereas particle size (Y1) and percentage entrapment efficiency (Y2) were considered as a response. The compatibility of ingredients with the drug was tested using differential scanning calorimetry. SLN were characterized for their particle size, entrapment efficiency, transmission electron microscopy, in vitro drug release, and ex vivo study. Results: The solid lipid nanoparticles were successfully prepared using high pressure homogenization technique and glyceryl monostearate was used as solid lipid. The lipid ratio significantly increases the particle size as well as entrapment efficiency. The particle size and (%) entrapment efficiency of optimized formulation were found to be 29 nm and 78.9%, respectively. The differential scanning calorimetry confirmed that the drug existed in amorphous form. Nasal histopathology study on sheep mucosa revealed that the developed SLN was non-toxic and safe to use for intranasal administration. The results of ex vivo study showed that the Higuchi pattern of drug release was followed. The in vitro release studies showed the significant difference in drug release from ITZ-loaded SLN compared to plain ITZ-solution. Conclusion: ITZ-loaded SLN were successfully prepared and validated. The best batch was selected based on the desired particle size, and EE which is an important characteristic for SLN formulations. The developed formulations were nontoxic as determined by histo-pathological studies.

Diosmin-loaded solid nanoparticles as nano-antioxidant therapy for management of hepatocellular carcinoma: QbD-based optimization, in vitro and in vivo evaluation

The present work focuses on the development and evaluation of the diosmin-loaded solid lipid nanoparticles (SLNs) with the goal of improving its therapeutic efficacy in hepatic carcinoma (HCC) treatment. HCC was induced by administration of diethyl nitrosamine (DEN) intraperitoneally at a dose of 200 mg/kg in male Wistar rats. The formulation and optimization of diosmin-loaded SLNs was performed using a five-factor and two-level full factorial design. The optimized SLNs exhibited particle size of 37.48 nm, polydispersity index of 0.29 nm, entrapment efficiency of 73.46% and drug loading capacity of 9.075%. In vitro drug release analysis of SLNs performed with dialysis bag technique revealed cumulative drug release >60% in 6 h. In vitro cytotoxicity study of diosmin-SLNs on HepG2 cells showed relatively higher cytotoxicity than diosmin solution and blank SLN. After 48 h of treatment, IC50 values for the diosmin-SLNs and diosmin solution were found to be 22.01 μg/mL and 33.11 μg/mL, respectively. In vivo animal study demonstrated that the hepatic DEN group rats shown hepatic nodules and antioxidant parameters that were altered by the diosmin in a dose-related fashion dramatically (p < 0.001). Diosmin-SLNs demonstrated strongest chemotherapeutic activity against DEN-induced HCC rats over diosmin solution, via the regulation of antioxidant mechanism-induced hepatic parameters. Overall, the studies indicated potential improvement in the biopharmaceutical and anticancer activity of the diosmin loaded in SLNs.

Formulation and evaluation of rutin-loaded solid lipid nanoparticles for the treatment of brain tumor.

The primary requirement for curing cancer is the delivery of essential drug load at the cancer microenvironment with therapeutic efficacy. Considering this, the present study aims to formulate "Rutin"-encapsulated solid lipid nanoparticles (SLNs) for effective brain delivery across the blood-brain barrier (BBB). Rutin-loaded SLNs were fabricated by oil-in-water microemulsion technique and were characterized for their physicochemical properties. The in vivo biodistribution study of rutin-loaded SLNs was studied using Rattus norvegicus rats. Subsequently, in silico molecular docking and dynamic calculations were performed to examine the binding affinity as well as stability of rutin at the active site of target protein "epidermal growth factor receptor (EGFR)." Formulated rutin-loaded SLNs were predominantly spherical in shape with an average particle diameter of 100nm. Additionally, the biocompatibility and stability have been proved in vitro. The presence and biodistribution of rutin in vivo after 54h of injection were observed as 15.23 ± 0.32% in the brain, 8.68 ± 0.63% in the heart, 4.78 ± 0.28% in the kidney, 5.04 ± 0.37% in the liver, 0.92 ± 0.04% in the lung, and 11.52 ± 0.65% in the spleen, respectively. Molecular docking results revealed the higher binding energy of - 150.973kJ/mol of rutin with EGFR. Molecular dynamic simulation studies demonstrated that rutin with EGFR receptor complex was highly stable at 30ns. The observed results exemplified that the formulated rutin-loaded SLNs were stable in circulation for a period up to 5days. Thus, rutin-encapsulated SLN formulations can be used as a promising vector to target tumors across BBB. Graphical abstract.

Solid Lipid Nanoparticles for Oral Drug Delivery: A Review

Background: The high molecular weight and increasing lipophilicity of drug face many problems starting from the drug development to formulation and conduction of pharmacological, toxicological and pharmacokinetic studies to its biological application. To overcome this problem, nano-sized formulations are in trend recently. The use of Solid lipid nanoparticles (SLNs) offers new insight into the formulation of the poor soluble and low bioavailable drug. Objective: The study aimed to investigate the literature concerning the development of SLNs for oral drug delivery of poorly soluble drugs, with a view survey the various methods of manufacturing and evaluation of formulation of SLNs and future prospects of SLNs and application of SLNs in oral delivery systems. Conclusion: Oral drug delivery is looking ahead progressively into newer directions due to the realization of various poor performance limiting factors such as reduced drug solubility or absorption, rapid metabolism, high actuation in plasma level of drug and variability caused due to food effect. These play a vital role in disappointing in vivo results, which leads in the failure of the conventional delivery system. Since the last decade, oral drug delivery has taken a new dimension with the increasing application of SLNs as a carrier for the delivery of poorly water-soluble or lipophilic drugs. The site-specific and sustained release effect of the drug is better achieved by using SLNs. This review highlights the various pros and cons, manufacturing techniques, characterization, and future prospects of SLNs in oral drug delivery systems.

Formulation and Evaluation of Solid Lipid Nanoparticles of Olanzapine for the Treatment of Psychosis

Solid lipid nanoparticles (SLN) are typically spherical with an average diameter between 1 nm to 1000 nm in range. It is alternative carrier systems to tradition colloidal carriers, such as liposomes emulsions and polymeric micro and nanoparticles. Olanzapine (OZP) is an atypical antipsychotic agent which is used for treatment of Schizophrenia. Its oral bioavailability is around of 40%. OZP is a class II drug so it having low aqueous solubility. To overcome that problem and to increase its bioavailability, the solid lipid nanoparticles of olanzapine are prepared. Formulation batches designed by modifying type of surfactant ( Span 80, Tween 80), concentration of surfactant, Concentration of co-surfactant, type of lipid ( glyceryl monostearate, Stearic acid), Lipid concentration, speed of stirring and time of stirring using customised design of DOE. The SLN were prepared by high speed homogenization technique, and then characterized by particle size analysis, Drug entrapment efficiency and Drug diffusion study. A formulation containing GMS as a lipid stabilised with tween 80 as surfactant show good drug release, smaller particle size, as compared with other formulations with different lipid and surfactant. The present research findings indicate that OZP loaded solid lipid Nano particulate system for delivery of OZP with better efficacy with minimum adverse effects. Keywords: Olanzapine, SLN, GMS, high speed homogenization and DOE.

Transcutol® P Containing SLNs for Improving 8-Methoxypsoralen Skin Delivery.

Topical psoralens plus ultraviolet A radiation (PUVA) therapy consists in the topical application of 8-methoxypsoralen (8-MOP) followed by the skin irradiation with ultraviolet A radiation. The employment of classical 8-MOP vehicles in topical PUVA therapy is associated with poor skin deposition and weak skin permeability of psoralens, thus requiring frequent drug administration. The aim of the present work was to formulate solid lipid nanoparticles (SLNs) able to increase the skin permeation of 8-MOP. For this purpose, the penetration enhancer Transcutol® P (TRC) was added to the SLN formulation. SLNs were characterized with respect to size, polydispersity index, zeta potential, entrapment efficiency, morphology, stability, and biocompatibility. Finally, 8-MOP skin diffusion and distribution within the skin layers was investigated using Franz cells and newborn pig skin. Freshly prepared nanoparticles showed spherical shape, mean diameters ranging between 120 and 133 nm, a fairly narrow size distribution, highly negative ζ potential values, and high entrapment efficiency. Empty and loaded formulations were almost stable over 30 days. In vitro penetration and permeation studies demonstrated a greater 8-MOP accumulation in each skin layer after SLN TRC 2% and TRC 4% application than that after SLN TRC 0% application. Finally, the results of experiments on 3T3 fibroblasts showed that the incorporation of TRC into SLNs could enhance the cellular uptake of nanoparticles, but it did not increase their cytotoxicity.

Formulation and Evaluation of Leflunomide Loaded Magnetic Solid-Lipid Nanoparticles for The Targeted Therapy of Breast Cancer

Formulation and Evaluation of Leflunomide Loaded Magnetic Solid-Lipid Nanoparticles for The Targeted Therapy of Breast Cancer

Formulation and Evaluation of Solid Lipid Nanoparticles of Bifonazole

The objective of this study was to develop suitable solid lipid nanoparticles for topical delivery of Bifonazole. Bifonazole is an imidazole antifungal drug used in form of ointments. It was patented in 1974 and approved for medical use in 1983. Bifonazole having broad spectrum activity against dermatophytes, moulds, yeasts, fungi and some gram positive bacteria. BFZ SLNs systems were developed by melt emulsification followed by solvent evaporation technique using Compritol 888ATO (Glyceryl behenate) as a solid lipid and Tween 80 as a surfactant. Developed SLNs were evaluated for particle size, polydispersity index (PI), entrapment efficiency (EE) and drug release profiles. Process and formulation parameters were optimized. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies were carried out on SLNs to mark the changes in the drug and lipid modifications. The BFZ SLNs based gels were prepared using Carbopol 940 as a gelling agent. The SLNs based gels were evaluated for rheological parameters, in vitro drug release and permeation studies. In vitro antifungal study suggested that the SLNs based gel was more effective in inhibiting growth of Candida albicans. Thus the study concludes that SLNs based gel of BFZ gives a sustained release profile of BFZ and has the potential for treatment of topical fungal infections.

Selection of Cryoprotectant in Lyophilization of Progesterone-Loaded Stearic Acid Solid Lipid Nanoparticles.

Cryoprotectants are often required in lyophilization to reduce or eliminate agglomeration of solute or suspended materials. The aim of this study was to select a cryoprotecting agent and optimize its concentration in a solid lipid nanoparticle formulation. Progesterone-loaded stearic acid solid lipid nanoparticles (SA-P SLNs) were prepared by hot homogenization with high speed mixing and sonication. The stearic acid content was 4.6% w/w and progesterone was 0.46% w/w of the initial formulation. Multiple surfactants were evaluated, and a lecithin and sodium taurocholate system was chosen. Three concentrations of surfactant were then evaluated, and a concentration of 2% w/w was chosen based on particle size, polydispersity, and zeta potential. Agglomeration of SA-P SLNs after lyophilization was observed as measured by increased particle size. Dextran, glycine, mannitol, polyvinylpyrrolidone (PVP), sorbitol, and trehalose were evaluated as cryoprotectants by both an initial freeze–thaw analysis and after lyophilization. Once selected as the cryoprotectant, trehalose was evaluated at 5%, 10%, 15%, and 20% for optimal concentration, with 20% trehalose being finally selected as the level of choice. Evaluation by DSC confirmed intimate interaction between stearic acid and progesterone in the SA-P SLNs, and polarized light microscopy shows successful lyophilization of the trehalose/SA-P SLN. A short term 28-day stability study suggests the need for refrigeration of the final lyophilized SA-P SLNs in moisture vapor impermeable packaging.

Phytol-Loaded Solid Lipid Nanoparticles as a Novel Anticandidal Nanobiotechnological Approach.

Phytol is a diterpene alcohol and can be found as a product of the metabolism of chlorophyll in plants. This compound has been explored as a potential antimicrobial agent, but it is insoluble in water. In this study, we describe a novel approach for an interesting anticandidal drug delivery system containing phytol. Different formulations of phytol-loaded solid lipid nanoparticles (SLN) were designed and tested using a natural lipid, 1,3-distearyl-2-oleyl-glycerol (TG1). Different compositions were considered to obtain three formulations with 1:10, 1:5, and 1:3 w/w phytol/TG1 ratios. All the formulations were prepared by emulsification solvent evaporation method and had their physicochemical properties assessed. The biocompatibility assay was performed in the HEK-293 cell line and the antifungal efficacy was demonstrated in different strains of Candida ssp., including different clinical isolates. Spherical and uniform SLN (<300 nm, PdI < 0.2) with phytol-loading efficiency >65% were achieved. Phytol-loaded SLN showed a dose-dependent cytotoxic effect in the HEK-293 cell line. The three tested formulations of phytol-loaded SLN considerably enhanced the minimal inhibitory concentration of phytol against 15 strains of Candida spp. Considering the clinical isolates, the formulations containing the highest phytol/TG1 ratios showed MICs at 100%. Thus, the feasibility and potential of phytol-loaded SLN was demonstrated in vitro, being a promising nanocarrier for phytol delivery from an anticandidal approach.

Lipid Nanoparticles for Enhancing the Physicochemical Stability and Topical Skin Delivery of Orobol.

Orobol is one of the major soy isoflavones, and has been reported to have various pharmacological activities, including an anti-skin-aging effect. However, since it has low solubility in water and physicochemical instability, the formulation of orobol for delivery into the dermal layer of the skin could be challenging. The objective of this study was to prepare lipid nanoparticles formulations of orobol to enhance its stability as well as its deposition into the skin. Formulations of orobol-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were characterized in terms of their mean particle size, entrapment efficiency, and morphology. The nano-sized spherical NLCs formulations maintained the stability of orobol for up to 28 days. Moreover, the NLCs formulation significantly increased the in vitro deposition of orobol into both Strat-M membranes and human cadaver skin compared with the other formulations. Additionally, the NLCs formulation did not cause significant skin irritation in clinical study. These results demonstrate that a shea butter-based NLC formulation could be a promising and safe carrier system for improving the stability of orobol and enhancing its topical skin delivery.

Development and Statistical Optimization of Solid Lipid Nanoparticle Formulations of Fluticasone Propionate.

The aim of this study was to develop fluticasone propionate (FP)-loaded solid lipid nanoparticle (SLN) formulations by using factorial design approach. Tristearin percentages (X1) (1%, 2%, and 4%) and homogenization cycles (X2) (2, 4, and 8 cycles) were selected as independent variables in the factorial design. SLN formulations were optimized by multiple linear regression (MLR) to evaluate the influence of the selected process and formulation independent variables on SLNs' characteristics, namely as encapsulation efficiency (Q1) and particle size (Q2). The polydispersity index and surface charge of the SLNs were also evaluated in this research. Moreover, transmission electron microscopy, differential scanning calorimetry, and in vitro drug release studies were carried out on the optimum SLN formulation. The MLR analysis indicated that as the homogenization cycle (X2) increased in the production process, the mean particle size decreased. This research showed that FP-encapsulated SLNs with desired characteristics can be produced by varying the production and content variables of the formulations.

FORMULATION, DEVELOPMENT AND CHARACTERISATION OF NIMODIPINE LOADED SOLID LIPID NANOPARTICLES

Objective: The aim of the present study is to develop solid lipid nanoparticles (SLNs) of Nimodipine using hot homogenization followed by ultrasonication technique and to improve the dissolution characteristics of the drug.&#x0D; Methods: The Nimodipine-loaded SLN was prepared using palmitic acid and stearic acid as a lipid matrix and Tween-80 as an emulsifier by a hot homogenization and ultra-sonication method. The physicochemical characteristics of SLN were investigated for entrapment efficiency, zeta potential, in vitro drug release, particle size analysis, Fourier transform infrared studies, scanning electron microscopy, and stability studies.&#x0D; Results: The mean particle size, PDI, Zeta potential and entrapment efficiency of optimized Nimodipine SLN formulation of stearic acid was found to be 119.54 nm, 0.165,-17.60mV, 85% and for palmitic acid was found to be 132.54 nm, 0.155,-17.0mV, 81% respectively. In vitro drug release studies indicated that after an initial burst release, SLN could provide prolonged release of Nimodipine. The selected SLNs have shown good stability for a period of 180 d.&#x0D; Conclusion: SLN formulations showed the best results in EE as well as in vitro drug release and therefore, these results indicate that SLN might be a promising delivery system to enhance the release of Nimodipine.

Formulation and pharmacokinetic evaluation of rifampicin solid lipid nanoparticles

Formulation and pharmacokinetic evaluation of rifampicin solid lipid nanoparticles

Curcumin Containing PEGylated Solid Lipid Nanoparticles for Systemic Administration: A Preliminary Study.

Curcumin (CUR) has a wide range of pharmacological properties, including anti-inflammatory and antioxidant activities, and it can be considered a good candidate for the potential treatment of central nervous system (CNS) pathologies, although its use in clinical practice is compromised due to its high lipophilicity. Solid lipid nanoparticles (SLNs) are well-known nanocarriers representing a consolidated approach for the delivery of lipophilic compounds, but their systemic use is limited due their short half-life. The formulation of stealth SLNs (pSLNs) could be a valid strategy to overcome this limit. Curcumin-loaded-pSLNs were prepared by the solvent evaporation method. Formulation was characterized for their mean size, zeta potential, size distribution, and morphology. Drug antioxidant activity was evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay. Finally, the obtained formulations were analyzed in terms of long-term stability. Curcumin-loaded-pSLNs showed good technological parameters with a mean particle size below 200 nm, as confirmed by TEM images, and a zeta potential value around −30 mV, predicting good long-term stability. Differential Scanning Calorimetry (DSC) analysis confirmed that PEG micelles interacted with the SLN surface; this suggests the location of the PEG on the pSLN surface. Therefore, these preliminary studies suggest that the produced formulation could be regarded as a promising carrier for the systemic administration.

Enhancement of ciprofloxacin activity by incorporating it in solid lipid nanoparticles

Purpose: To incorporate ciprofloxacin (CIP) into solid lipid nanoparticles (SLN) in order to enhance its biopharmaceutical properties and antibacterial activity.Methods: A sonication melt-emulsification method was employed for the preparation of CIP-loaded SLN. The composition of the SLN was varied in order to investigate factors such as lipid type and combination ratio, drug to lipid ratio, and surfactant ratio. The produced SLN formulations wereevaluated for their particle size and shape, zeta potential, and entrapment efficiency. In addition, the effect of SLN formulation composition on its drug release profile and antimicrobial activity against Escherichia coli, Pseudomonas Aeruginosa, and Staphylococcus Aureus was also investigated.Results: The generated nanoparticles had particle size in the range of 165 to 320 nm. The zetapotential values were generally low within ± 5. All formulations exhibited entrapment efficiency between 50 and 90 %. CIP release exhibited a biphasic release profile with a low burst phase, followed by uniform controlled-release behavior of various rates. SLN-loaded CIP exhibited one-fold reduction in minimum inhibitory concentration (MIC) and caused significant inhibition of all the three bacterial strains tested, when compared with pure CIP.Conclusion: Loading of CIP into SLN significantly enhances its antimicrobial activity in vitro which can translate to significant enhancement of therapeutic outcomes by minimizing the dose-dependent adverse and side effects and/or enhancing the antimicrobial spectrum of activity.&#x0D; Keywords: Solid lipid nanoparticles, Sonication melt-emulsification, Ciprofloxacin, Escherichia coli, Pseudomonas aeruginosa

Preparation, Statistical Optimization and Characterization of Propolis-Loaded Solid Lipid Nanoparticles Using Box-Behnken Design.

Purpose: Propolis is a resinous material obtained by honeybees with many biological and pharmacological properties which can be used for treatment of various diseases. Current study aims to formulate and characterize propolis-loaded solid lipid nanoparticles (SLNs) carrier system. Methods: The prepared SLNs, composed of glyceryl monostearate (GMS), Soy lecithin, Tween 80 and polyethylene glycol 400 (PEG 400), were fabricated employing solvent emulsification-evaporation technique. In addition, the impact of several variables including concentration ratios of GMS/Soy lecithin and PEG 400/Tween 80 along with emulsification time were evaluated on the size, polydispersity index (PDI) and zeta potential of particles. SLN formulations were optimized using Box-Behnken design. The particles were freeze dried and morphologically studied by scanning electron microscopy (SEM). The in-vitro release profile of propolis entrapped in the optimized nanoparticles was investigated. Results: The mean particle size, PDI, zeta potential, entrapment efficiency (EE) and loading efficiency (LE) of optimized propolis-loaded SLNs were found to be 122.6±22.36 nm, 0.28±0.06, -26.18±3.3 mV, 73.57±0.86% and 3.29±0.27%, respectively. SEM images exhibited nanoparticles to be non-aggregated and in spherical shape. The in-vitro release study showed prolonged release of propolis from nanoparticles. Conclusion: The results implied that the proposed way of SLN preparation could be considered as a proper method for production of propolis loaded colloidal carrier system.