Lipid nanoparticles of zaleplon for improved oral delivery by Box–Behnken design: optimization,in vitro and in vivo evaluation

Purpose: Zaleplon (ZL) is a hypnotic drug prescribed for the management of insomnia and convulsions. The oral bioavailability of ZL was low (～30%) owing to poor water solubility and hepatic first-pass metabolism. The cornerstone of this investigation is to develop and optimize solid lipid nanoparticles (SLNs) of ZL with the aid of Box–Behnken design (BBD) to improve the oral bioavailability.

Methods: A design space with three formulation variables at three levels were evaluated in BBD. Amount of lipid (A₁), amount of surfactant (A₂) and concentration of co-surfactant (%) (A₃) were selected as independent variables, whereas, particle size (B₁), entrapment efficiency (B₂) and zeta potential (ZP, B₃) as responses. ZL-SLNs were prepared by hot homogenization with ultrasonication method and evaluated for responses to obtain optimized formulation. Morphology of nanoparticles was observed under SEM. DSC and XRD studies were examined to understand the native crystalline behavior of drug in SLN formulations. Further, in vivo studies were performed in Wistar rats.

Results: The optimized formulation with 132.89?mg of lipid, 106.7?mg of surfactant and 0.2% w/v of co-surfactant ensued in the nanoparticles with 219.9?±?3.7?nm of size, ?25.66?±?2.83?mV surface charge and 86.83?±?2.65% of entrapment efficiency. SEM studies confirmed the spherical shape of SLN formulations. The DSC and XRD studies revealed the transformation of crystalline drug to amorphous form in SLN formulation. In conclusion, in vivo studies in male Wistar rats demonstrated an improvement in the oral bioavailability of ZL from SLN over control ZL suspension.

Conclusions: The enhancement in the oral bioavailability of ZL from SLNs, developed with the aid of BBD, explicated the potential of lipid-based nanoparticles as a potential carrier in improving the oral delivery of this poorly soluble drug.     

Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization,in vitro characterization,cell line studies and in vivo efficacy in schizophrenia

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration.

Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies.

Results: The LH-SLNs had PS of 139.8?±?5.5?nm, EE of 79.10?±?2.50% and zeta potential of ?30.8?±?3.5?mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia.

Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.     

Enhanced intestinal absorption and bioavailability of raloxifene hydrochloride via lyophilized solid lipid nanoparticles

The current oral therapy with raloxifene hydrochloride (RXH) is less effective due to its poor bioavailability (only 2%). Henceforth, an attempt was made to investigate the utility of triglyceride (trimyristin, tripalmitin and tristearin) based solid lipid nanoparticles (SLNs) for improved oral delivery of RXH. The SLN formulations prepared were evaluated for particle size, zeta potential and % entrapment and the optimized formulation was lyophilized. Solid state characterization studies unravel the transformation of RXH to amorphous or molecular state from the native crystalline form. Further the in situ perfusion studies carried out in rat intestine reveal the potential of SLN for enhanced permeation of raloxifene HCl across gastrointestinal barrier. To derive the conclusions, in vivo pharmacokinetic study was conducted in rats to assess the bioavailability of RXH from SLN formulation compared to drug suspension. Overall a twofold increase in bioavailability with SLN formulations confer their potential for improved oral delivery of RXH.     

In vitro and in vivo evaluation of cyclodextrin-based nanosponges for enhancing oral bioavailability of atorvastatin calcium

The aim of this study was to explore the feasibility of complexing the poorly water-soluble drug atorvastatin calcium (AC) with β-cyclodextrin (β-CD) based nanosponges (NS), which offer advantages of improving dissolution rate and eventually oral bioavailability. Blank NS were fabricated at first by reacting β-CD with the cross-linker carbonyldiimidazole at different molar ratios (1:2, 1:4, and 1:8), then NS of highest solubilization extent for AC were complexed with AC. AC loaded NS (AC-NS) were characterized for various physicochemical properties. Pharmacokinetic, pharmacodynamics and histological finding of AC-NS were performed in rats. The prepared AC-NS showed particles size ranged from 408.7?±?12.9 to 423?±?15.9?nm while zeta potential values varied from ?21.7?±?0.90 to ?22.7?±?0.85?mV. The loading capacity varied from 17.9?±?1.21 to 34.1?±?1.16%. DSC, FT–IR, and PXRD studies confirmed the complexation of AC with NS and amorphous state of the drug in the complex. AC-NS displayed a biphasic release pattern with increase in the dissolution rate of AC as compared to plain AC. Oral administration of AC-NS (1:4 w/w, drug: NS) to rats led to 2.13-folds increase in the bioavailability as compared to AC suspension. Pharmacodynamics studies in rats with fatty liver revealed significant reduction (p?in vivo performance of AC.     

Design and development of multiple emulsion for enhancement of oral bioavailability of acyclovir

The objective of this investigation was to design and develop water-in-oil-in-water type multiple emulsions (w/o/w emulsions) entrapping acyclovir for improving its oral bioavailability. Multiple emulsions (MEs) were prepared and optimized using Span-80 and Span-83 as lipophilic surfactant and Brij-35 as hydrophilic surfactant. The physio-chemical properties of the w/o/w emulsions - particle size, viscosity, phase separation (centrifugation test) and entrapment efficiency were measured and evaluated along with macroscopic and microscopic observations to confirm multiple nature, homogeneity and globule size. Stability study, in vitro and ex vivo release studies were performed followed by in vivo studies in rats. Stable w/o/w emulsions with a particle size of 33.098 ± 2.985 µm and 85.25 ± 4.865% entrapment efficiency were obtained. Stability studies showed that the concentration of lipophilic surfactant was very important for stability of MEs. Drug release from the prepared formulations showed initial rapid release followed by a much slower release. In vivo studies in rats indicated prolonged release and better oral bioavailability as compared to drug solution. The overall results of this study show the potential of the w/o/w emulsions as promising drug delivery systems for acyclovir.     

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation,design and in vivo evaluation

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56?±?8.57?nm, 0.27?±?0.028 and 83.66?±?5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p?0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.     

Sustained release of piroxicam from solid lipid nanoparticle as an effective anti-inflammatory therapeutics in vivo

Abstract

This study aims to investigate the solid lipid nanoparticle (SLN) as a novel vehicle for the sustained release and transdermal delivery of piroxicam, as well as to determine the anti-inflammation effect of piroxicam-loaded SLN. SLN formulation was optimized and the particle size, polydispersity index, zeta potential (ZP), encapsulation efficiency, drug release, and morphological properties were characterized. The transdermal efficiency and mechanism of the piroxicam-loaded SLNs were investigated in vitro. With the inflammation induced edema model in rat, the anti-inflammatory efficiency of piroxicam-enriched SLNs (Pir-SLNs) was evaluated. The SLN formulation was optimized as: lecithin 100?mg, glycerin monostearate 200?mg, and Tween (1%, w/w). The particle size is around 102?±?5.2?nm with a PDI of 0.262. The ZP is 30.21?±?2.05?mV. The prepared SLNs showed high entrapment efficiency of 87.5% for piroxicam. There is no interaction between piroxicam and the vehicle components. The presence of polymorphic form of lipid with higher drug content in the optimized Pir-SLNs enables the Pir-SLNs to release the drug with a sustained manner. Pir-SLNs with oleic acid as enhancer can radically diffuse into both the stratum corneum and dermal layer, as well as penetrate through the hair follicles and sebaceous glands with significantly higher density than the other control groups. Pir-SLNs promptly inhibited the inflammation since the 3rd hour after the treatment by decreasing the PGE₂ level. SLN was demonstrated to be a promising carrier for encapsulation and sustained release of piroxicam. Pir-SLN is a novel topical preparation with great potential for anti-inflammation application.     

Optimization of the lyophilization process for long-term stability of solid–lipid nanoparticles

Objectives: To optimize a lyophilization protocol for solid–lipid nanoparticles (SLNs) loaded with dexamethasone palmitate (Dex-P) and to compare the long-term stability of lyophilized SLNs and aqueous SLN suspensions at two storage conditions.

Materials and Methods: The effect of various parameters of the lyophilization process on SLN redispersibility was evaluated. A three month stability study was conducted to compare changes in the particle size and drug loading of lyophilized SLNs with SLNs stored as aqueous suspensions at either 4°C or 25°C/60% relative humidity (RH).

Results and Discussion: Of nine possible lyoprotectants tested, sucrose was shown to be the most efficient at achieving SLN redispersibility. Higher freezing temperatures, slower freezing rates, and longer secondary drying times were also shown to be beneficial. Loading of the SLNs with Dex-P led to slightly larger particle size and polydispersity index increases, but both parameters remained within an acceptable range. Drug loading and particle shape were maintained following lyophilization, and no large aggregates were detected. During the stability study, significant growth and drug loss were observed for aqueous SLN suspensions stored at 25°C/60% RH. In comparison, lyophilized SLNs stored at 4°C exhibited a consistent particle size and showed <20% drug loss. Other storage conditions led to intermediate results.

Conclusions: A lyophilization protocol was developed that allowed SLNs to be reconstituted with minimal changes in their physicochemical properties. During a three month period, lyophilized SLNs stored at 4°C exhibited the greatest stability, showing no change in the particle size and a minimal reduction in drug retention.     

Preparation,optimization, characterization and in vivo pharmacokinetic study of asiatic acid tromethamine salt-loaded solid lipid nanoparticles

Purpose: To enhance the oral bioavailability of asiatic acid tromethamine salt (AAS) by encapsulation in solid lipid nanoparticles (SLN).

Methods: The AAS-loaded SLN (AASLN) was prepared by the modified solvent injection method with glycerin monostearate (GMS) as lipid and poloxamer 188 as surfactant. A Box–Behnken design was used to optimize the formulations. Physicochemical characterization was carried out by using dynamic light scattering, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Stabilities at 4?°C and pH 1.2 were investigated by particle size or/and entrapment efficiency (EE%). The in vivo pharmacokinetics was evaluated by HPLC-MS/MS.

Results: The optimal formulation of AASLN had an average size of 237?nm with zeta potential of ?35.9?mV, and EE% of 64.4%. SEM showed that the AASLN had spherical shape with smooth surface. Furthermore, DSC and X-ray analyses indicated that AAS was amorphous state and the crystal degree of GMS was significantly decreased in the formulation. AASLN showed excellent stability at 4?°C for 1 month and no coacervation at pH 1.2. The bioavailability of AAS in SLN was found to be 2.5-fold higher than that of AAS alone after a single oral administration in rats.

Conclusions: This study reveals that SLN is developed as a promising oral delivery system of AAS with significantly enhanced bioavailability and good storage stability.     

Characterization and formulation optimization of solid lipid nanoparticles in vitamin K1 delivery

Background: Solid lipid nanoparticle (SLN) systems have been applied to various drugs and delivery routes. Vitamin K1 is an important cofactor for maintaining hemostasis and preventing hemorrhage. Method: Vitamin K1-loaded SLNs are systematically being developed by optimizing triglycerides and lipophilic and hydrophilic surfactants based on the size and stability of the resulting SLNs. Concentrations of the surfactants, Myverol and Pluronic, were optimized by a central composite design and response surface methodology. Vitamin K1 (phylloquinone) was used as a lipophilic drug in the SLN system to evaluate the potential for oral delivery. Results: Vitamin K1-loaded SLNs had a mean size of 125 nm and a zeta potential of ?23 mV as measured by photon correlation spectroscopy. The prepared SLNs were examined by differential scanning calorimetry and transmission electron microscopy and found to have an imperfect crystalline lattice and a spherical morphology. Effects of ultrasonication duration and drug load on the particle size and entrapment efficiency of the SLNs were also evaluated. Conclusion: More than 85% of the vitamin K1 was entrapped in SLNs when the payload was <5%. The vitamin K1 in SLNs was stable for a 54-h duration in simulated gastric and intestinal fluids. The particle size and vitamin K1 entrapped in the SLN were stable after 4 months of storage at 25°C. The results demonstrated that SLNs prepared herein can potentially be exploited as carriers for the oral delivery of vitamin K1.     

Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation,optimization and in vivo evaluation

Objective: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery.

Materials and methods: Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug–excipients interactions, powder X-ray diffraction analysis and drug release in vitro.

Results and discussion: The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100?nm, PDI 0.291, zeta potential of ?23.4?mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration.

Conclusion: In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.     

Histopathological evaluation of caffeine-loaded solid lipid nanoparticles in efficient treatment of cellulite

Context: Cellulite refers to dimpled appearance of the skin, usually located in the thighs and buttocks regions of most adult women.

Objective: The aim of this study was to formulate topically used caffeine-loaded solid lipid nanoparticle (SLN) for the treatment of cellulite.

Methods: SLNs were prepared by hot homogenization technique using Precirol® as lipid phase. The physical characterization and stability studies of SLNs as well as in vitro skin permeation and histological studies in rat skin were conducted.

Results: The mean particle size, encapsulation efficiency and loading efficiency percentages for optimized SLN formulation were 94?nm, 86 and 28%, respectively. In vitro drug release demonstrated that caffeine-loaded SLN incorporated into carbopol made hydrogel (caffeine-SLN-hydrogel) exhibited a sustained drug release compared to the caffeine hydrogel over 24?h. Caffeine-loaded SLNs showed a good stability during 12 months of storage at room temperature. The DSC and XRD results showed that caffeine was dispersed in SLN in an amorphous state. In vitro permeation studies illustrated higher drug accumulation in the skin with caffeine-SLN-hydrogel compared to caffeine hydrogel. The flux value of caffeine through rat skin in caffeine-SLN-hydrogel was 3.3 times less than caffeine hydrogel, representing lower systemic absorption. In contrast with caffeine hydrogel, the histological studies showed the complete lysis of adipocytes by administration of caffeine-SLN-hydrogel in the deeper skin layers.

Conclusion: Results of this study indicated that SLNs are promising carrier for improvement of caffeine efficiency in the treatment of cellulite following topical application on the skin.     

Solid lipid nanoparticles of anticancer drug andrographolide: formulation,in vitro and in vivo studies

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (C_max), area under the curve (AUC), etc. There was an improvement in C_max and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The t_max was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.     

Oral solid compritol 888 ATO nanosuspension of simvastatin: optimization and biodistribution studies

The purpose of the present investigation was to develop solid lipid nanoparticles (SLNs) of simvastatin in order to enhance its oral bioavailability by minimizing its first-pass metabolism. To achieve our goal, SLNs were prepared by solvent injection technique and optimized by 2³ full factorial experimental design using Design Expert software. The SLN formulations were optimized for amount of compritol, concentration of poloxamer, and volume of acetone in order to achieve desired responses of particle size, entrapment efficiency (EE), and cumulative drug release (CDR). Response surface plots were constructed to study the influence of each variable on each response and the interactions between any two variables were also analyzed. Formulation F₁₀ with particle size of 271.18?nm, % EE of 68.16% and % CDR of 76.23%, and highest desirability value of 0.645 was selected as optimized formulation. The optimized formulation was evaluated for biodistribution and pharmacokinetics by technetium-99m (Tc-99m) radiolabeling technique in mice. The relative bioavailability of simvastatin from optimized SLNs was found to be 220%, substantiating the protective action of SLNs against liver metabolism. However, though the drug initially bypassed the liver metabolism, simvastatin continuously entered in liver to exert its therapeutic action that was evidenced by biodistribution study.     

Capecitabine lipid nanoparticles for anti-colon cancer activity in 1,2-dimethylhydrazine-induced colon cancer: preparation,cytotoxic, pharmacokinetic,and pathological evaluation

The cornerstone of this investigation is to determine the pharmacokinetic and histopathological behavior of solid lipid nanoparticles of capecitabine (CB-SLNs) in 1,2-dimethylhydrazine (DMH) induced colon cancer. The nanoparticles were prepared by microemulsion method. CB-SLNs were characterized for an optimal system. The cytotoxicity of CB-SLNs was evaluated by using MTT assay method. Further, pharmacokinetic and histopathological behavior of SLNs were studied in DMH induced colon cancer rats. The optimized nanoparticles have the particle size, zeta potential, and entrapment efficiency of 145.6?±?3.6?nm, ?26.9?±?2.7?mV, and 88.33?±?3.74%, respectively. Particles of CB were nearly spherical in shape and converted to amorphous form revealed by SEM and DSC, XRD studies. The nanoparticles showed dose-dependent cytotoxicity activity from 10 to 125?µg/mL compared with suspension. Pharmacokinetic studies revealed that 2.7-folds enhancement in the oral bioavailability and in aberrant crypt foci number, apoptotic index comparison with suspension formulation.     

Bortezomib-loaded solid lipid nanoparticles: preparation,characterization, and intestinal permeability investigation

Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6?±?0.66?nm with a negative surface charge of –18?±?11?mV. The entrapment efficiency of the BTZ-SLNs was 68.3?±?3.7% with a drug loading value of 0.8?±?0.05%. Cumulative drug release (%) over 48?h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a P_eff value of about threefold higher than plain BTZ solution.     

Nanosuspension of efavirenz for improved oral bioavailability: formulation optimization,in vitro,in situ and in vivo evaluation

Context: Nanosuspensions (NSs) of poorly water-soluble drugs are known to increase the oral bioavailability.

Objectives: The purpose of this study was to develop NS of efavirenz (EFV) and to investigate its potential in enhancing the oral bioavailability of EFV.

Materials and methods: EFV NS was prepared using the media milling technique. The Box–Behnken design was used for optimization of the factors affecting EFV NS. Sodium lauryl sulfate and PVP K30 were used to stabilize the NS. Freeze-dried NS was completely re-dispersed with double-distilled filtered water.

Results: Mean particle size and zeta potential of the optimized NS were found to be 320.4?±?3.62?nm and –32.8?±?0.4 mV, respectively. X-ray diffraction and differential scanning calorimetric analysis indicated no phase transitions. Rate and extent of drug dissolution in the dissolution medium for NS was significantly higher compared to marketed formulation. The parallel artificial membrane permeability assay revealed that NS successfully enhanced the permeation of EFV. Results of in situ absorption studies showed a significant difference in absorption parameters such as K_a, t_1/2 and uptake percentages between lyophilized NS and marketed formulation of EFV. Oral bioavailability of EFV in rabbits resulting from NS was increased by 2.19-fold compared to the marketed formulation.

Conclusion: Thus, it can be concluded that NS formulation of EFV can provide improved oral bioavailability due to enhanced solubility, dissolution velocity, permeability and hence absorption.     

Oral solid compritol 888 ATO nanosuspension of simvastatin: optimization and biodistribution studies

The purpose of the present investigation was to develop solid lipid nanoparticles (SLNs) of simvastatin in order to enhance its oral bioavailability by minimizing its first-pass metabolism. To achieve our goal, SLNs were prepared by solvent injection technique and optimized by 2(3) full factorial experimental design using Design Expert software. The SLN formulations were optimized for amount of compritol, concentration of poloxamer, and volume of acetone in order to achieve desired responses of particle size, entrapment efficiency (EE), and cumulative drug release (CDR). Response surface plots were constructed to study the influence of each variable on each response and the interactions between any two variables were also analyzed. Formulation F(10) with particle size of 271.18?nm, % EE of 68.16% and % CDR of 76.23%, and highest desirability value of 0.645 was selected as optimized formulation. The optimized formulation was evaluated for biodistribution and pharmacokinetics by technetium-99m (Tc-99m) radiolabeling technique in mice. The relative bioavailability of simvastatin from optimized SLNs was found to be 220%, substantiating the protective action of SLNs against liver metabolism. However, though the drug initially bypassed the liver metabolism, simvastatin continuously entered in liver to exert its therapeutic action that was evidenced by biodistribution study.     

Preparation and characterization of solid lipid nanoparticles of furosemide using quality by design

The present work aimed to synthesize solid lipid nanoparticles (SLNs) of Furosemide (FRSM). The parameter sensitivity analysis showed a significant effect of particle size and reference solubility on the AUC_0–∞, C_max and t_max. The FRSM-encapsulated SLNs were synthesized by the phase inversion temperature (PIT) technique using 3² factorial design. The optimal level of 221.28?mg of Compritol 888 ATO and 420?mg of Cremophor RH 40 showed a mean hydrodynamic diameter (MHD) of 25.54?±?0.57?nm, a polydispersity index (PdI) of 0.158?±?0.01, the % entrapment efficiency of 80.70?±?4.06%, percent dissolution efficiency of 71.72?±?1.52% and time elapsed for 50% drug release of 3.67?±?0.15?h. The PIT was determined using the turbidity method and the values ranged between 75°C and 73°C. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) images represent spherical to sub-spherical and smooth surface of SLN. The Fourier transform-infrared (FTIR), differential scanning calorimetry (DSC) and x-ray diffraction (XRD) depict the drug-excipient compatibility. Korsmeyer–Peppas was found to be the best fit release kinetics model (R²?=?0.973; K-value?=?29.96 and release exponent?=?0.40), predicting the Fickian diffusion. The results advocate that the optimized formulation (OF) could promote the controlled release, and improve the physicochemical stability of the formulation. Hence, SLN could be a potential drug carrier for the peroral delivery of FRSM.     

Formulation-optimization of solid lipid nanocarrier system of STAT3 inhibitor to improve its activity in triple negative breast cancer cells

In the present study, solid lipid nanoparticles (SLNs) have been formulated as a carrier system for effective intracellular delivery of STAT3 inhibitor, niclosamide (Niclo) to triple negative breast cancer (TNBC) cells. Emulsification-solvent evaporation method was employed in formulation of Niclo-loaded SLNs (Niclo-SLNs). The formula of Niclo-SLN was optimized by Box–Behnken design and characterized for their shape, size, and surface charge. The in vitro anti-cancer efficacy of Niclo-SLNs was studied in TNBC cells. The prepared Niclo-SLNs were found to be spherical with the particle size of 112.18?±?1.73?nm and zetapotential of 23.8?±?2.7?mV. In the in vitro anticancer study the Niclo SLNs show a better cytotoxicity than the naïve Niclo, which is attributed to improved cell uptake of SLN formulation. In conclusion, the results of the present study demonstrate that the formulation of Niclo as SLNs will improve the anticancer efficacy against TNBC.