Optimization Of Solid Lipid Nanoparticles Research Articles

Sulconazole-Loaded Solid Lipid Nanoparticles for Enhanced Antifungal Activity: In Vitro and In Vivo Approach.

Solid lipid nanoparticles (SLNs) have the advantages of a cell-specific delivery and sustained release of hydrophobic drugs that can be exploited against infectious diseases. The topical delivery of hydrophobic drugs needs pharmaceutical strategies to enhance drug permeation, which is a challenge faced by conventional formulations containing a drug suspended in gel, creams or ointments. We report the fabrication and optimization of SLNs with sulconazole (SCZ) as a model hydrophobic drug and then a formulation of an SLN-based topical gel against fungal infections. The SLNs were optimized through excipients of glyceryl monostearate and Phospholipon® 90 H as lipids and tween 20 as a surfactant for its size, drug entrapment and sustained release and resistance against aggregation. The SCZ-SLNs were physically characterized for their particle size (89.81 ± 2.64), polydispersity index (0.311 ± 0.07), zeta potential (-26.98 ± 1.19) and encapsulation efficiency (86.52 ± 0.53). The SCZ-SLNs showed sustained release of 85.29% drug at the 12 h timepoint. The TEM results demonstrated spherical morphology, while DSC, XRD and FTIR showed the compatibility of the drug inside SLNs. SCZ-SLNs were incorporated into a gel using carbopol and were further optimized for their rheological behavior, pH, homogeneity and spreadability on the skin. The antifungal activity against Candida albicans and Trichophyton rubrum was increased in comparison to a SCZ carbopol-based gel. In vivo antifungal activity in rabbits presented faster healing of skin fungal infections. The histopathological examination of the treated skin from rabbits presented restoration of the dermal architecture. In summary, the approach of formulating SLNs into a topical gel presented an advantageous drug delivery system against mycosis.

Design and Optimization of Solid Lipid Nanoparticles Loaded with Triamcinolone Acetonide.

Principles of quality by design and design of experiments are acquiring more importance in the discovery and application of new drug carriers, such as solid lipid nanoparticles. In this work, an optimized synthesis of solid lipid nanoparticles loaded with Triamcinolone Acetonide is presented using an approach that involves Stearic Acid as a lipid, soy PC as an ionic surfactant, and Tween 80 as a nonionic surfactant. The constructed circumscribed Central Composite Design considers the lipid and nonionic surfactant quantities and the sonication amplitude in order to optimize particle size and Zeta potential, both measured by means of Dynamic Light Scattering, while the separation of unentrapped drug from the optimized Triamcinolone Acetonide-loaded solid lipid nanoparticles formulation is performed by Size Exclusion Chromatography and, subsequently, the encapsulation efficiency is determined by HPLC-DAD. The proposed optimized formulation-with the goal of maximizing Zeta potential and minimizing particle size-has shown good accordance with predicted values of Zeta potential and dimensions, as well as a high value of encapsulated Triamcinolone Acetonide. Experimental values obtained from the optimized synthesis reports a dimension of 683 ± 5 nm, which differs by 3% from the predicted value, and a Zeta potential of -38.0 ± 7.6 mV (12% difference from the predicted value).

Ocular Delivery of Bimatoprost-Loaded Solid Lipid Nanoparticles for Effective Management of Glaucoma.

Glaucoma is a progressive optic neuropathy characterized by a rise in the intraocular pressure (IOP) leading to optic nerve damage. Bimatoprost is a prostaglandin analogue used to reduce the elevated IOP in patients with glaucoma. The currently available dosage forms for Bimatoprost suffer from relatively low ocular bioavailability. The objective of this study was to fabricate and optimize solid lipid nanoparticles (SLNs) containing Bimatoprost for ocular administration for the management of glaucoma. Bimatoprost-loaded SLNs were fabricated by solvent evaporation/ultrasonication technique. Glyceryl Monostearate (GMS) was adopted as solid lipid and poloxamer 407 as surfactant. Optimization of SLNs was conducted by central composite design. The optimized formulation was assessed for average particle size, entrapment efficiency (%), zeta potential, surface morphology, drug release study, sterility test, isotonicity test, Hen's egg test-chorioallantoic membrane (HET-CAM) test and histopathology studies. The optimized Bimatoprost-loaded SLNs formulation had an average size of 183.3 ± 13.3 nm, zeta potential of -9.96 ± 1.2 mV, and encapsulation efficiency percentage of 71.8 ± 1.1%. Transmission electron microscopy (TEM) study revealed the nearly smooth surface of formulated particles with a nano-scale size range. In addition, SLNs significantly sustained Bimatoprost release for up to 12 h, compared to free drug (p < 005). Most importantly, HET-CAM test nullified the irritancy of the formulation was verified its tolerability upon ocular use, as manifested by a significant reduction in mean irritation score, compared to positive control (1% sodium dodecyl sulfate; p < 0.001). Histopathology study inferred the absence of any signs of cornea tissue damage upon treatment with Bimatoprost optimized formulation. Collectively, it was concluded that SLNs might represent a viable vehicle for enhancing the corneal permeation and ocular bioavailability of Bimatoprost for the management of glaucoma.

Design, Characterization and Optimization of Solid Lipid Nanoparticles of Bupropion by Using 23 Factorial Design

Design, Characterization and Optimization of Solid Lipid Nanoparticles of Bupropion by Using 23 Factorial Design

Design, Development and Optimization of Solid Lipid Nanoparticles for Ocular Delivery of an Antifungal Agent

Oral and intravenous dosing of the second-generation antifungal drug voriconazole (VCZ), with its wide range of antifungal action, is commercially accessible. Visual and hepatic problems might occur when VCZ is used in large doses. Voriconazole SLNs were prepared in this study with the goal of increasing corneal penetration and drug release. The thin fi lm hydration approach was used to make VCZ SLNs. The central composite experimental design was used to maximize the impacts of independent processing factors on vesicle size (R1), drug entrapment effi ciency (%EE) and zeta potential (ZP; R3) responses on lipid concentration (X1), surfactant concentration (X2), and sonication duration (X3). An evaluation of the drug release profi le, corneal penetration, antifungal susceptibility, and cytotoxicity of the improved formula was conducted. The improved recipe achieved the best results with a ZP of -39.6 ± 0.28 mV, an average particle size of 156 ± 3.84 nm, and an EE% of 89.2 ± 2.01. When compared to the unformulated drug solution, the VCZ-SLNs had a prolonged 10 hours drug release profi le with improved corneal penetration, with Papp and Jss measuring 14.35×10-2 cm h-1 and 4.61 mol h-1, respectively, instead of 7.28×10-2 cm h-1 and 2.48 mol h-1. Non-irritating VCZ-SLNs were determined to be corneal tissue, according to the study. Improved corneal penetration and higher antifungal activity without harmful eff ects on ocular tissues were achieved by VCZ-SLNs

Development, characterization and optimization of solid lipid nanoparticles of alpha-mangostin by central composite design approach

Development, characterization and optimization of solid lipid nanoparticles of alpha-mangostin by central composite design approach

Development and optimization of solid lipid nanoparticles coated with chitosan and poly(2-ethyl-2-oxazoline) for ocular drug delivery of ciprofloxacin

Many formulation strategies have been employed to improve ocular bioavailability of topical eye drops. The aim of this study was to develop and evaluate a series of solid lipid nanoparticles coated with poly(2-ethyl-2-oxazoline) and chitosan for ocular delivery of ciprofloxacin. Ciprofloxacin-loaded poly(2-ethyl-2-oxazoline) (PSLN) formulation was prepared by a combination of melt-emulsion sonication and low-temperature solidification methods. A Box-Behnken design, was employed to statistically optimize the effects of the amount of drug (X1), lipid:polymer ratio (X2) and surfactant concentration (X3) on particle size (Y1) and entrapment efficiency (Y2). Analysis of variance was used to validate the optimization design; and regression equations and response surface plots were generated. The optimized formulation was selected through numerical point prediction approach. These nanoparticles were characterized using dynamic light scattering, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). In vitro drug release and corneal permeation studies were carried out, while the mucoadhesive properties were evaluated ex vivo using porcine corneal tissue. The particle size and zeta potential of the optimized formulations ranged from 141 to 213 nm and +24.6 to −35.6 mV, respectively. PSLN possessed higher encapsulation efficiency than chitosan-coated solid lipid nanoparticles (CSLN). The in vitro drug release from all the formulations showed an initial burst release followed by prolonged release over 24 h. The release mechanism followed Korsemeyer-Peppas model and Fickian diffusion (n < 0.5). DSC revealed lower enthalpy and crystallinity of the formulations as also detected by PXRD, while TEM showed spherical particles in the lower nanometer range with a layer of polymer coating. The results of this study demonstrated that CSLN exhibited higher mucoadhesion and retention on corneal tissues compared with PSLN and also showed higher flux and apparent permeability, but with lower entrapment efficiency.

Systematic Optimization of Solid Lipid Nanoparticles of Silybin for Improved Oral Drug Delivery by Box-Behnken Design: In Vitro and In Vivo Evaluations

Systematic Optimization of Solid Lipid Nanoparticles of Silybin for Improved Oral Drug Delivery by Box-Behnken Design: In Vitro and In Vivo Evaluations

Preparation, evaluation and optimization of solid lipid nanoparticles composed of pantoprazole

Nanoparticles are a promising medication delivery method that can deliver drugs in a controlled and targeted manner. They're made to release the medicine in close proximity to the target tissue. Solid lipid nanoparticles (SLNs) are a new type of submicron-sized lipid emulsion in which solid lipid replaces liquid lipid (oil). The goal of this study was to create solid lipid nanoparticles (SLN) containing pantoprazole (a proton pump inhibitor) and improve the drug's entrapment efficiency in SLN. This was accomplished by integrating the medication into solvent-injection-prepared solid lipid nanoparticles (SLN). During formulation development, the component concentrations were optimized, and then the particles were characterized in terms of particle size, zeta potential, drug loading, percent drug entrapment, stability studies, and drug release behavior. There was no interaction between the medication and the excipients in FT-IR experiments. The improved formulation's percent EE, particle size, and drug content were found to be 91.88±1.38, 7.16±0.26µm and 97.20±1.46 respectively. F6 was shown to be the most promising formulation among all created formulations in this investigation. For 30 days, stability tests were conducted (F6) at refrigerated temperature (4.0±0.2°C), room temperature (25-28±2°C), and 45±1°C. The current project also aims to improve the formulation's pharmacological acceptability.&#x0D; Keywords: Solid lipid nanoparticles, Pantoprazole, Solvent-injection method, Entrapment efficiency

Design, Development and Optimization of Solid Lipid Nanoparticles of Rizatriptan for Intranasal delivery: Invitro & Invivo assessment

Solid lipid nanoparticles were at the frontline of the rapid development of nanotechnology, with several potential applications in drug administration. Because of their unique size-dependent properties, solid lipid nanoparticles have the potential to produce innovative treatments. The capacity to incorporate drugs into nanocarriers allows for the creation of a revolutionary drug delivery prototype that might be utilized for targeting novel drugs to the brain. RZT benzoate intra nasal formulation would be a practical, non-invasive, & alternative method of fast drug delivery to the brain for migraine treatment. Poloxamer-containing solid lipid nanoparticles having mucoadhesive characteristics improve drug absorption by increasing contact duration at the nasal mucosa. Shape, surface morphology, particle size, FTIR, DSC, X-ray diffraction tests, drug entrapment, total drug content, and in vitro drug release studies were all performed on RZT-loaded solid lipid nanoparticles created utilizing a modified solvent diffusion method. There was a wide range in particle size from 124.9 to 467.2 nm for these lipid nanoparticles, all of which were spherical and smooth on the outside. There was a maximum in vitro drug release of 92.6% in 24 h, a drug content of 45–55%, and a maximum entrapment efficacy of 78.6 percent. When administered through the nose, RZT benzoate may be more bioavailable than when taken orally, overcoming the first-pass impact and allowing for a long-term therapy plan for acute migraine.

Central Composite Design for Formulation and Optimization of Solid Lipid Nanoparticles to Enhance Oral Bioavailability of Acyclovir.

Treatment of herpes simplex infection requires high and frequent doses of oral acyclovir to attain its maximum therapeutic effect. The current therapeutic regimen of acyclovir is known to cause unwarranted dose-related adverse effects, including acute kidney injury. For this reason, a suitable delivery system for acyclovir was developed to improve the pharmacokinetic limitations and ultimately administer the drug at a lower dose and/or less frequently. In this study, solid lipid nanoparticles were designed to improve the oral bioavailability of acyclovir. The central composite design was applied to investigate the influence of the materials on the physicochemical properties of the solid lipid nanoparticles, and the optimized formulation was further characterized. Solid lipid nanoparticles formulated from Compritol 888 ATO resulted in a particle size of 108.67 ± 1.03 nm with an entrapment efficiency of 91.05 ± 0.75%. The analyses showed that the optimum combination of surfactant and solid lipid produced solid lipid nanoparticles of good quality with controlled release property and was stable at refrigerated and room temperature for at least 3 months. A five-fold increase in oral bioavailability of acyclovir-loaded solid lipid nanoparticles was observed in rats compared to commercial acyclovir suspension. This study has presented promising results that solid lipid nanoparticles could potentially be used as an oral drug delivery vehicle for acyclovir due to their excellent properties.

Optimization of Solid Lipid Nanoparticles and Nanostructured Lipidic Carriers as Promising Delivery for Gefitinib: Characterization and Invitro Evaluation

Background: Response surface methodology is a unique tool for the optimization of Solid lipid Nanoparticles and Nanostructured lipid carriers by developing the relationship between dependent and independent variables and exploring their interactions. Methods: Central Composite Design and Box Benkhen Design was used to develop optimized formulations of Gefitinib [GEF] Solid Lipid Nanoparticles [SLN] and Nanostructured Lipidic Carriers [NLC]. In the design matrix, the independent variables chosen were the amount of Solid Lipid, Liquid Lipid, and Surfactant and dependent variables were Particle Size and Poly Dispersity Index. Result: The GEF-SLN under optimized conditions gave rise to Particle size (187.9 nm ± 1.15), PDI (0.318 ± 0.006), %EE (95.38%±0.14), Zeta Potential (-8.75 mv ±0.18) and GEF-NLC under optimized conditions gave rise to Particle size (188.6 nm± 1.12), PDI (0.395± 0.004), %EE (97.46%± 0.33), Zeta Potential (-5.72 mv± 0.04) respectively. SEM of the Freeze-dried optimized lipidic carriers showed spherical particles. The in vitro experiments proved that Gefitinib in the lipidic carriers is released gradually throughout 24 h. Conclusion: This study showed that the response surface methodology could be efficiently applied for the modeling of GEF-SLN &amp; GEF-NLC.

Evaluation and Comparison of Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Vectors to Develop Hydrochlorothiazide Effective and Safe Pediatric Oral Liquid Formulations.

The aim of this study was the optimization of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in terms of physicochemical and biopharmaceutical properties, to develop effective and stable aqueous liquid formulations of hydrochlorothiazide, suitable for paediatric therapy, overcoming its low-solubility and poor-stability problems. Based on solubility studies, Precirol® ATO5 and Transcutol® HP were used as solid and liquid lipids, respectively. The effect of different surfactants, also in different combinations and at different amounts, on particle size, homogeneity and surface-charge of nanoparticles was carefully investigated. The best formulations were selected for drug loading, and evaluated also for entrapment efficiency and release behaviour. For both SLN and NLC series, the use of Gelucire® 44/14 as surfactant rather than PluronicF68 or Tween® 80 yielded a marked particle size reduction (95–75 nm compared to around 600–400 nm), and an improvement in entrapment efficiency and drug release rate. NLC showed a better performance than SLN, reaching about 90% entrapped drug (vs. 80%) and more than 90% drug released after 300 min (vs. about 65%). All selected formulations showed good physical stability during 6-month storage at 4 °C, but a higher loss of encapsulated drug was found for SLNs (15%) than for NLCs (<5%). Moreover, all selected formulations revealed the absence of any cytotoxic effect, as assessed by a cell-viability test on Caco-2 cells and are able to pass the intestinal epithelium as suggested by Caco-2 uptake experiments.

Optimization of Solid Lipid Nanoparticles of Ezetimibe in Combination with Simvastatin Using Quality by Design (QbD)

Background: The objective of this study was to develop solid lipid nanoparticles (SLNs) of poorly water soluble anti-hyperlipidemic drugs-Ezetimibe in combination with Simvastatin. Methods: This study describes a 32 full factorial experimental design to optimize the formulation of drug loaded lipid nanoparticles (SLN) by the high speed homogenization technique. The independent variables amount of lipid (GMS) and amount of surfactant (Poloxamer 188) were studied at three levels and arranged in a 32 factorial design to study the influence on the response variables- particle size, % entrapment efficiency (%EE) and cumulative drug release (% CDR) at 24 h. Results: The particle size, % EE and % CDR at 24 h for the 9 batches (B1 to B9) showed a wide variation of 104.6-496.6 nm, 47.80-82.05% (Simvastatin); 48.60-84.23% (Ezetimibe) and 54.64-92.27% (Simvastatin); 43.8-97.1% (Ezetimibe), respectively. The responses of the design were analysed using Design Expert 10.0.2. (Stat-Ease, Inc, USA), and the analytical tools of software were used to draw response surface plots. From the statistical analysis of data, polynomial equations were generated. Optimized formulation showed particle size of 169.5 nm, % EE of 75.43% (Simvastatin); 79.10% (Ezetimibe) and 74.13% (Simvastatin); 77.11% (Ezetimibe) %CDR after 24 h. Thermal analysis of prepared solid lipid nanoparticles gave indication of solubilisation of drugs within lipid matrix. Conclusion: Fourier Transformation Infrared Spectroscopy (FTIR) showed the absence of new bands for loaded solid lipid nanoparticles indicating no interaction between drugs and lipid matrix and being only dissolved in it. Electron microscope of transmission techniques indicated sphere form of prepared solid lipid nanoparticles with smooth surface with size approximately around 100 nm.

Formulation and Optimization of Solid-Lipid Nano-particles of the Anticancer Drug Bortezomib

Solid-lipid nanoparticles (SLNs) are an alternative carrier system used for loading the drug for targeting, improving the bioavailability by increasing its solubility, and protecting the drug from presystemic metabolism. The avoidance of presystemic metabolism is due to the nanometric size range so that the liver cannot uptake the drug from the delivery system and is not metabolized by the liver. Bortezomib is an anti-cancer drug. Due to its poor oral bioavailability, presystemic metabolism and decreased half-life, it was chosen to formulate as the SLN system with the use of a 3-factor, 3-level Box–Behnken design, by hot homogenization followed by an ultrasonication method. Trimyristin (Dynasan-114), tripalmitin (Dynasan 116) and tristearin (Dynasan-118) were used as lipids and based on the results from the initial studies tripalmitin (Dynasan116) was selected as the lipid for the further studies along with phosphatidylcholine as surfactant and Poloxamer 188 as stabilizer. The optimized formulation (F1) was obtained with minimum particle size (204 nm), maximum entrapment efficiency (70.24) and drug loading (21.24). The optimised batches were further investigated by FTIR, DSC, XRD, SEM and stability. In vitro release studies showed that maximum cumulative drug release was obtained for F1 (99.74%). The optimized formulation Bortezomib followed zero-order release kinetics with a strong correlation coefficient (R2= 0.9994). The nanoformulation prepared under optimized conditions is in concurrence with the expected results. It is concluded that the SLN formulation can be used as a potential carrier for the effective delivery of Bortezomib.

Formulation Development and Optimization of Simvastatin Loaded Solid Lipid Nanoparticles

The present research work support preformulation, formulation, development and optimization of solid lipid nanoparticles containing simvastatin as an antihyperlipidemic drug. The different batches of formulation were obtained using simvastatin as active pharmaceutical ingredient, stearic acid as the source of lipid and β-cyclodextrin as a polymer. Solid lipid nanoparticles of simvastatin were prepared by precipitation method. The prepared formulations were evaluated for various parameters like Particle size, Percentage entrapment efficiency, Measurement of Zeta Potential, FTIR, in-vitro release study. The result was found to be within standard limit. FTIR study reports indicated that there was no interaction between Simvastatin and other excipients. Motic microscope shown that the nanoparticles size ranges from 100-550nm. Percent entrapment efficiency was between 61.40%-92.30%. Based on the resultants of the entrapment and particle size of nanoparticles, formulation S6 was observed to be optimized formulation. The optimized formulation exhibited 63.75% cumulative drug release after 24 h. The optimized batch shows mean of zeta potential at-44.0 mV.

Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability.

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients.

Transport features and structural optimization of solid lipid nanoparticles crossing the intestinal epithelium

In vitrosimulated intestinal epithelial cell monolayer is a novel avenue to screen optimal SLNs formulations.

Application of Box–Behnken design for preparation of levofloxacin-loaded stearic acid solid lipid nanoparticles for ocular delivery: Optimization, in vitro release, ocular tolerance, and antibacterial activity

The aim of the present study was to develop and optimize levofloxacin loaded solid lipid nanoparticles for the treatment of conjunctivitis. Box–Behnken experimental design was applied for optimization of solid lipid nanoparticles. The independent variables were stearic acid as lipid (X1), Tween 80 as surfactant (X2) and sodium deoxycholate as co-surfactant (X3) while particle size (Y1) and entrapment efficiency (Y2) were the dependent variables. Further in vitro release and antibacterial activity in vitro were also performed. The optimized formulation of levofloxacin provides particle size of 237.82nm and showed 78.71% entrapment efficiency and achieved flux 0.2493μg/cm2/h across excised goat cornea. In vitro release study showed prolonged drug release from the optimized formulation following Korsmeyer–Peppas model. Antimicrobial study revealed that the developed formulation possesses antibacterial activity against Staphylococcus aureus, and Escherichia coli equivalent to marketed eye drops. HET-CAM test demonstrated that optimized formulation was found to be non-irritant and safe for topical ophthalmic use. Our results concluded that solid lipid nanoparticles are an efficient carrier for ocular delivery of levofloxacin and other drugs.

Optimization of solid lipid nanoparticles prepared by a single emulsification-solvent evaporation method.

This data article contains the data related to the research article “Characterization, biorecognitive activity and stability of WGA grafted lipid nanostructures for the controlled delivery of rifampicin” (Pooja et al. 2015) [1]. In the present study, SLN were prepared by a single emulsification-solvent evaporation method and the various steps of SLN preparation are shown in a flow chart. The preparation of SLN was optimized for various formulation variables including type and quantity of lipid, surfactant, amount of co-surfactant and volume of organic phase. Similarly, effect of variables related to homogezation, sonication and stirring processes, on the size and surface potential of SLN was determined and optimized.