Curcumin-loaded Nanostructured Lipid Carriers Research Articles

Hyaluronic acid-decorated lipid nanocarriers as novel vehicles for curcumin: Improved stability, cellular absorption, and anti-inflammatory effects

This study aimed to investigate how hyaluronic acid interfacial decoration affects the stability, cellular absorption, and anti-inflammatory effects of curcumin-loaded nanostructured lipid carriers. Nanocarriers were synthesized with an ovalbumin single layer and ovalbumin/hyaluronic acid double, mixed, or conjugated layers. All nanocarriers were spherical (200–300 nm diameter), and their encapsulation efficiency exceeded 95 %. Among the layers, the conjugated one exhibited the highest elastic surface dilatational modulus of approximately 40 mN/m, and the longest curcumin half-life of 186.07 days at 4 °C. Spearman's correlation analysis showed a negative correlation (r = −0.6698) between the recrystallization index and curcumin stability. The layer's mechanical strength improved curcumin stability by preventing crystal transition. Hyaluronic acid decoration enhanced the curcumin uptake of Caco-2 cells by 1.96–2.48 folds. Among the layers, the conjugate one was the most effective because of its strong binding constant with the receptor. Hyaluronic acid decoration improved the anti-inflammatory effects of curcumin.

Design and Characterisation of Curcumin-Loaded Nanostructured Lipid Carriers for Safe and Efficient Topical Drug Delivery in The Treatment of Pressure Ulcer

Pressure ulcers (PU) are chronic lesions with a high prevalence in at-risk populations. Although curcumin has various therapeutic properties, its use as a dermal therapeutic agent is limited by its poor solubility and permeability. This study aimed to develop nanostructured lipid carriers (NLCs) to facilitate the topical use of curcumin as wound healing agent in treating PU. The optimised curcumin-NLCs were characterised for their physicochemical properties, drug release, and skin permeation, while effectiveness and toxicity were investigated via cell viability, scratch assays, and an in vivo skin irritation test. The optimised curcumin-NLCs comprised 3.5% solid lipids, 1% surfactant, and 2% co-surfactant with an average particle size of 134.68±6.0 nm, polydispersity index of 0.248±0.00, zeta potential of −44.94±5.44, percentage of encapsulation efficiency of 93.42±0.32%, and drug loading of 0.11±0.00%. Curcumin-NLCs showed stable physicochemical properties and extended drug release for up to 48 h, with a cumulative release of 77.72% following a first-order kinetics. The formulation exhibited slower curcumin permeation than the free curcumin. Furthermore, the safe and non-toxic curcumin-NLCs were highly effective at 0.98 μM and showed a high rate of wound closure without skin irritation. Collectively, the NLCs developed for topical delivery of curcumin demonstrated prolonged and sustained release and improved wound healing activity, which indicates that curcumin-NLCs are a viable strategy for treating PU.

The impact of particle size of nanostructured lipid carriers on follicular drug delivery: A comprehensive analysis of mouse and human hair follicle penetration.

Follicular delivery is one of the targeted drug delivery methods aiming to target the hair follicles. The accumulation and retention time of targeted drugs is enhanced when nanoparticles are used as drug carriers. Particle size is one of the important factors affecting the penetration and accumulation of particles in the hair follicles, and there is a controversy in different studies for the best particle size for follicular delivery. Mouse models are mostly used in clinical trials for dermal, transdermal, and follicular delivery studies. Also, it is essential to investigate the reliability of the results between human studies and mouse models. Curcumin-loaded nanostructured lipid carriers (NLCs), as a fluorescent agent, with three different particle size ranges were prepared using the hot homogenization method and applied topically on the mouse and human study groups. Biopsies were taken from applied areas on different days after using the formulation. The histopathology studies were done on the skin biopsies of both groups using confocal laser scanning microscopy (CLSM). We compared the confocal laser scanning microscope pictures of different groups, in terms of penetration and retention time of nanoparticles in human and mouse hair follicles. The best particle size in both models was the 400 nm group but the penetration and accumulation of particles in human and mouse hair follicles were totally different even for the 400 nm group. In human studies, 400 nm particles showed good accumulation after seven days; this result can help to increase the formulation using intervals. The best particle size for human and mouse follicular drug delivery is around 400 nm and although mouse models are not completely suitable for follicular delivery studies, they can be used in some conditions as experimental models.

Impact of cocoa butter and medium chain triglycerides ratios on processing stability, supersaturation, and digestive properties of curcumin-loaded nanostructured lipid carriers

In the pursuit of optimal delivery of hydrophobic agents such as curcumin, the role of lipid composition in the efficacy of nanostructured lipid carriers is gaining significant attention. This study aimed to investigate the effects of cocoa butter (0–10 wt%) and medium chain triglycerides oil (0–10 wt%) mass ratios on processing stability, crystallization, polymorphism transition, supersaturation, encapsulation, and in vitro digestion of curcumin-loaded nanostructured lipid carriers (Cur-NLCs). Transmission electron microscopy (TEM) analysis showed that spherical Cur-NLCs exhibited larger average particle size with the increase in cocoa butter content. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed that the crystallinity and thickness of solid shells decreased with the increase in liquid lipid content. The obtained Cur-NLCs remained stable under various conditions: thermal treatments (25, 37, 60, and 121 °C), varied ionic strengths (50–500 mM), pH changes (2.0–6.0), centrifugation (21382×g for 40 min), and 60-days storage. Furthermore, Cur-NLCs showed higher supersaturation (1863 ± 20–2328 ± 10%) than that of nanoemulsion (1489 ± 6%) and solid lipid nanoparticles (1635 ± 36%). In addition, the prepared Cur-NLCs exhibited high bioaccessibility (79.4 ± 3.1–91.1 ± 2.1%) along with a controlled release of curcumin. This study provides guidelines to prepare Cur-NLCs with tailored physicochemical, functional, and digestion properties to deliver hydrophobic bioactive substances, nutraceuticals, and pharmaceuticals.

Optimization and evaluation of microwave-assisted curcumin-loaded nanostructured lipid carriers: a green approach

BackgroundThe goal of current research work is to develop and optimize curcumin-encapsulated nanostructured lipid carriers and to enhance therapeutic effect of curcumin after oral administration.MethodCurcumin-loaded nanostructured lipid carriers were developed by a single-step one-pot microwave-assisted technique. The preparation of curcumin-loaded nanostructured lipid carriers was optimized by employing two factors and three levels central composite design (Design Expert® software) taking concentration of lipid blend and surfactant as independent variables and particle size, polydispersity index, and zeta potential as dependent variables, to investigate the effect of formulation ingredients on the physicochemical characteristics of nanostructured lipid carriers. The optimized batch was investigated by Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, high-resolution transmission electron microscopy, in vitro drug release, stability studies, cytotoxicity, and in vivo anthelmintic studies.ResultsThe average particle size, polydispersity index, and zeta potential of the optimized batch were found to be 144 nm, 0.301, and − 33.2 mV, respectively, with an entrapment efficiency of 92.48%. The results of high-resolution transmission electron microscopy confirmed spherical shape of particles. In vivo antiparasitic studies included determining the duration of paralysis and eventual death of earthworms in the presence of test samples. The results of in vivo studies showed good anthelmintic potential for curcumin-loaded nanostructured lipid carriers as compared to albendazole in different concentrations. Cytotoxicity studies also confirmed the formulation to be nontoxic to Vero cells. In vitro drug release study showed 90.76 ± 0.01% release of curcumin in 24 h by following the Korsmeyer-Peppas model of release kinetics.ConclusionThe aforementioned results imply that microwave-developed nanostructured lipid carriers could be promising drug carriers and will aid in their fabrication for oral administration as a possible alternative for the treatment of other parasitic infections.Graphical

Effects of Preparation Temperature and Liquid-Solid Lipid Composition to Curcumin-Nanostructured Lipid Carrier Characteristics Fabricated by Microfluidic Technique

Nanostructured Lipid Carriers (NLC) are lipid-based carrier that uses a combination of liquid and solid lipids which is believed to deliver a higher amount of active substance to the human body. This study aimed to obtain the best formulation and evaluate the stability of curcuminloaded NLC (C-NLC) using microfluidic technique at temperature of 40o C and 60o C with the ratios of liquid:solid lipids were 2 : 1 ; 3.5 : 1 ; 4 : 1 ; 6 : 1% w/w. Our results showed that the increase of process temperature and liquid lipid concentration reduced particle size. There was a non-linear relationship between lipid ratio and temperature to encapsulation percentage. At ratio of soybean oil:stearic acid 6 : 1 and, at 40°C, particles size (PS) obtained was 143.87 ± 3.36 nm, polydispersity index (PDI) obtained was 0.44 ± 0.01, zeta potential (ZP) obtained was -33.3 ± 6.53 mV with encapsulation percentage of 20.62%. At the same ratio at 60°C, the PS obtained was 60.21 ± 2.55 nm, PDI obtained was 0.72 ± 0.03, ZP obtained was -26.10 ± 1.83 mV and encapsulation percentage of 31.45%. Stability test showed that C-NLC produced at 60°C was more stable since the change of particle size and pH were lower than C-NLC produced at 40°C.

Topical delivery of Bruton’s tyrosine kinase inhibitor and curcumin-loaded nanostructured lipid carrier gel: Repurposing strategy for the psoriasis management

This work investigates the synergistic potential of the nanostructured lipid carrier (NLC) gel of Ibrutinib with Curcumin as a repurposing strategy to treat psoriasis. In the present work, various components such as liquid lipid, solid lipid, and surfactant were selected and optimized based on the solubility of each drug, size, and polydispersity index. The optimized NLC consists of Capryol PGMC as liquid lipid, Glyceryl Mono Stearate as solid lipid, and Pluronics-F-127 as a surfactant. The prepared NLCs have a particle size of 95.12 ± 3.39 nm with PDI of 0.285 ± 0.009, exhibiting high entrapment efficiency (86.04 ± 2.86% for IBR and 87.25 ± 2.14% for CUR) with spherical geometry. CI value of 0.283 suggests synergism. Carbopol 940 was used as a gelling agent and has shown improved flux compared to plain drug gel. Anti-psoriatic studies in BALB/c mice indicated negligible skin irritation and improved histopathological features of psoriasis. Moreover, a reduced amount of inflammatory markers (TNF-alpha, IL-6, IL-22, and IL-23), and psoriasis severity score was observed with prepared gel than the IMQ group. The study suggested integrated benefits of repurposing Ibrutinib with Curcumin as NLC topical gel and it could possibly reduce remission of Psoriasis like inflammation and merit additional investigation.

Digestion stability of curcumin-loaded nanostructured lipid carrier

Curcumin is known as a functional substance with various effects such as antioxidant, anti-inflammatory, and anticancer. However, it is not easily utilized due to low water solubility and bioavailability. Therefore, this study encapsulated into a nanostructured lipid carrier (NLC) with MCT oil of coconut to improve the solubility of insoluble curcumin. The physicochemical properties and stability of curcumin NLCs were observed, and the in vitro gastrointestinal stability of curcumin NLCs was also studied. The produced curcumin NLCs had a hydrodynamic diameter of 126.9 nm, zeta potential of −25.9 mV, PDI of 0.246, and encapsulation efficiency of 94.5%. TGA and DSC analysis were performed to confirm the thermal properties (pyrolysis temperature (°C), weight loss (%), melting temperature (°C), and crystallinity, etc.) of the components constituting the curcumin NLCs. Through this, it was confirmed that curcumin was completely entrapped in the NLC structure. In the digestive imitation system, NLCs released approximately 31% of curcumin in the imitation saliva step, and curcumin release gradually increased. This study showed that NLCs were an effective carrier to apply in various fields such as the functional food industry, because they increased the water solubility of curcumin and could also improve bioavailability and curcumin storage stability.

Observation of curcumin-loaded hydroxypropyl methylcellulose (HPMC) oleogels under in vitro lipid digestion and in situ intestinal absorption in rats

Curcumin-loaded nanostructured lipid carriers (Cur-NLCs)-based hydroxypropyl methylcellulose (HPMC) oleogels (Cur-NLCs-HPMC-OGs) were fabricated using a cryogel template. The effect of the HPMC viscosity grade on the oleogel characteristics and in situ intestinal absorption were examined. Highly stable Cur-NLCs were prepared with a mean particle size of 314 nm and polydispersity index of 0.275. Cur-NLCs affected the creamy texture of self-standing Cur-NLCs-HPMC-OGs. The Cur-NLCs were tightly packed as oil droplets in the network of HPMC. However, a high viscosity of HPMC-4000 led to a greater ability to entrap and prevent droplet coalescence compared to a low viscosity of HPMC-400. NLCs promoted the release of free fatty acids during in vitro lipid digestion, whereas HPMC-4000 maintained the strength and durability of oleogels against mechanical and enzymatic breakdown. The in situ loop results revealed higher curcumin absorption by Cur-NLCs-HPMC-OGs than by Cur-HPMC-OGs. HMPC-4000 showed slightly higher curcumin absorption compared to HPMC-400.

Interfacial engineering strategy to improve the stabilizing effect of curcumin-loaded nanostructured lipid carriers

In this work, the interfacial structure of nanostructured lipid carriers (NLCs) stabilized by whey protein isolate (single layer NLCs, S-NLCs) was modified with polysaccharide through two approaches: 1) electrostatic deposition of a polysaccharide layer onto the surface of S-NLCs affording double layer NLCs (D-NLCs); 2) heating the protein-polysaccharide complexes to promote biopolymer assembly, which were utilized as emulsifiers for the composite layer NLCs (C-NLCs). S-NLCs presented a spherical shape, hydrodynamic diameter of about 300 nm and curcumin (Cur) encapsulation efficiency below 30%. However, these values changed following interfacial decoration of NLCs. The interfacial viscoelastic studies suggested that the type 2 strategy enabled a more compact and elastic stabilizing layer than the type 1 method, as the interfacial biopolymers of the former were held together by multiple interactions. Therefore, C-NLCs showed higher capacity to inhibit polymorphic transition or degradation of Cur than other NLCs. Both approaches could slow down the lipolysis rate as well as decrease the lipolysis degree of NLCs during simulated digestion, while increase the bioavailability of the entrapped Cur. Besides, the highest cellular antioxidant activity was observed for Cur in C-NLCs, followed by D-NLCs and S-NLCs, in accordance to the stabilizing effects of these NLCs for the loaded agent.

FORMULATION OPTIMIZATION, CHARACTERIZATION AND IN VITRO ANTI-CANCER ACTIVITY OF CURCUMIN LOADED NANOSTRUCTURED LIPID CARRIERS

Objective: The present study was aimed at preparing stable lyophilized curcumin loaded nanostructured lipid carriers (NLCs). The optimized lyophilized curcumin loaded NLCs were characterized and evaluated for various quality control parameters. Methods: The optimized curcumin loaded NLCs were prepared by modified hot emulsification using precirol ATO 5 (PRE), capmul MCM C8 EP (CAP) as solid and liquid lipids, respectively. The combination of tween 80 (T80) and solutol HS 15 (SHS) were used as an emulsifier. The NLCs dispersion was lyophilized into powder form to improve the thermodynamic stability of the formulation. The lyophilized curcumin loaded NLCs were evaluated for particle size, size distribution, zeta potential, entrapment efficiency (EE), drug loading, assay, in vitro drug release, crystallinity and surface morphology studies. Results: The optimized lyophilized curcumin loaded NLCs have a mean particle size of 286.2±11.5 nm with a size distribution of 0.288±0.011, a zeta potential of 0.247±0.025 mV with high entrapment of 98.20±1.53 % and drug loading of 2.50±0.21 %. The X-ray diffraction and endothermic peaks confirmed the maximum encapsulation of curcumin in lipid matrices. The particles were spherical with smooth surface morphology. In vitro release studies showed sustained release for up to 24 h. The cytotoxicity against human lung cancer line A-549 for curcumin-loaded NLCs was confirmed with positive control adriamycin (ADR). Conclusion: Curcumin-loaded NLCs prepared had a nanosize particle distribution with maximum entrapment efficiency. Dispersion stability was increased by the lyophilisation process. The solid lyophilized powder is reconstituted for oral delivery.

Enhanced neuroprotective and antidepressant activity of curcumin-loaded nanostructured lipid carriers in lipopolysaccharide-induced depression and anxiety rat model

The present study aims to develop curcumin-loaded nanostructured lipid carriers (CUR-NLCs) and investigate their neuroprotective effects in lipopolysaccharide (LPS)-induced depression and anxiety model. Nanotemplate engineering technique was used to prepare CUR-NLCs with Compritol 888 ATO and oleic acid as solid and liquid lipid, respectively. Poloxamer 188, Tween 80 and Span 80 were used as stabilizing agents for solid–liquid lipid core. The physicochemical parameters of CUR-NLCs were determined followed by in vitro drug release and in vivo neuroprotective activity in rats. The optimized CUR-NLCs demonstrated nanometric particle size of 147.8 nm, surface charge of –32.8 mV and incorporation efficiency of 91.0%. CUR-NLCs showed initial rapid followed by a sustained drug release reaching up to 73% after 24 h. CUR-NLCs significantly elevated struggling time and decreased immobility time in forced swim and tail suspension tests. A substantial increase in time spent and number of entries into the light and open compartments was observed in light–dark box and elevated plus maze models. CUR-NLCs improved the tissue architecture and suppressed the expression of p-NF-κB, TNF-α and COX-2 in brain tissues from histological and immunohistochemical analysis. CUR-NLCs improved the neuroprotective effect of curcumin and can be used as a potential therapeutics for depression and anxiety.

Eco-friendly curcumin-loaded nanostructured lipid carrier as an efficient antibacterial for hospital wastewater treatment

Abstract The contamination of wastewater with a wide variety of chemical, microbiological and toxic substances is an area of increasing environmental concern. The present study aimed to introduce a new strategy to remove a variety of bacterial pathogens from hospital wastewater. Eco-friendly curcumin loaded nanostructured lipid carriers (NLC-curcumin) were prepared by the hot high-speed homogenization method. The average particle size and zeta potential of NLC-curcumin were 137.9 ± 3.21 nm and -23.36 ± 3.5 mV, respectively. The nanoparticles were also characterized in terms of morphology, thermal behavior, antioxidant properties, and infrared spectroscopy. In vitro antibacterial effects of the NLC-curcumin and free-curcumin was studied by Turbidity assay in Luria–Bertani (LB) media on the standard and wild bacteria strains. The antibacterial effect of NLC-curcumin on bacteria was also studied by the SEM images. Analysis of colony forming unit per milliliter (CFU/ml) was used to evaluate the potential of NLC-curcumin on the bacteria growth decrease in the real environment of the hospital wastewater. The findings reveal that NLC-curcumin (0.125 μ M) in Mueller–Hinton agar media clearly reduces the percentage of the wild bacteria strains in autoclaved wastewater at 37 °C. For the original hospital wastewater treatment, NLC-Curcumin (0.125 μ M) significantly decreased the percentage of the microbial total count at 25 °C.

Curcumin-loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of the DR5/caspase-mediated extrinsic apoptosis pathway.

Curcumin is a lipophilic anti-cancer compound extracted from turmeric. Our previous study demonstrated that the curcumin-loaded nanostructured lipid carrier (Cur-NLC) exhibits superior anti-cancer activity in inhibiting proliferation as well as inducing apoptosis of human HepG2 cells compared to native curcumin. This study aims to unveil the mechanisms underlying the pro-apoptotic effect of Cur-NLC on HepG2 cells. Evidence indicates that low expression of death receptors (DRs) on cancer cell membranes leads to attenuated apoptosis signaling. This study showed that Cur-NLC significantly increased total expression of DR5 protein while simultaneously upregulated cell membrane expression of DR5. Cur-NLC significantly increased caspase-8 and caspase-3 activities, accompanied by increased apoptosis. Furthermore, enhanced apoptosis was inhibited in the presence of a pan-caspase inhibitor, Z-VAD-FMK. Therefore, Cur-NLC induced activation of the extrinsic apoptosis pathway via modulating the DR5/caspase-8/-3 mediated apoptosis pathway in HepG2 cells, suggesting that Cur-NLC is a promising therapeutic agent or supplement for the treatment of hepatocellular carcinoma.

In vivo Antiplasmodial Activity of Curcumin-Loaded Nanostructured Lipid Carriers.

It has been shown that curcumin (Cur) has anti-plasmodial activity; however, its weak bioavailability, rapid metabolism, and limited chemical stability have restricted its application in clinical usages. Nanostructured lipid carriers (NLCs) are a type of Drug-Delivery Systems (DDSs) whose core matrix is composed of both solid and liquid lipids. The aim of the current study was to prepare and characterize curcumin-loaded nanostructured lipid carriers (Cur-NLC) for malaria treatment. For producing NLC, coconut oil and cetyl palmitate were selected as a liquid and solid lipid, respectively. In order to prepare the Cur-NLC, the microemulsion method was applied. General toxicity assay on Artemia salina as well as hemocompatibility was investigated. Anti-plasmodial activity was studied on mice infected with Plasmodium berghei. The NLCs mean particle size and Polydispersity Index (PI) were 145 nm and 0.3, respectively. Further, the zeta potential of the Cur-NLC was -25 mV. The NLCs indicated a pseudo-spherical shape observed via transmission electron microscopy (TEM). The loading capacity and encapsulation efficacy of the obtained Cur-NLC were 3.1 ± 0.015% and 74 ± 3.32%, respectively. In vitro, Cur release profiles showed a sustained-release pattern up to 5 days in the synthesized Cur-NLC. The results of in vivo antiplasmodial activity against P. berghei revealed that antimalarial activity of Cur-NLC was significantly higher compared with that of free Cur at the dose of 40 mg/kg/day. The results of this study suggested that NLC would be used as a potential nanocarrier for the treatment of malaria.

Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside.

The objective of the present study was to investigate the effect of partially hydrolyzed ginsenoside on the physicochemical properties and in vitro release of curcumin from phospholipid-based nanostructured lipid carrier (NLC). NLC formulas modified with partially hydrolyzed ginsenoside (NLC-PG) were prepared with different amounts of ginsenoside using the conventional hot-melt method. The average particle size of curcumin-loaded NLC-PG ranged from 150 to 200nm, and polydispersity index was in the range of 0.101-0.177, indicating monodispersed particle size distribution. Optical microscopy showed no sedimentation or recrystallization of curcumin even at 10,000μg/ml concentration as NLC-PG in distilled water, indicating significantly enhanced solubility. TEM image showed that the nanoparticles were monodispersed with a multilayered core/shell structure. X-ray diffraction and FTIR spectroscopy showed that curcumin was amorphous in the NLC-PG, and there was no interaction between curcumin and the excipients. In vitro release study using simulated gastric/intestinal fluid media revealed that the release rate (Jss) of curcumin from the NLC-PG increased as a function of the ginsenoside content in the lipid carrier. Moreover, the Jss of curcumin kept gradually increasing in the presence of lipase, whereas in the presence of viscozyme, it sharply increased until the ginsenoside content reached 9.09% and subsequently plateaued. Partially hydrolyzed ginsenoside increased the Jss of curcumin from curcumin-loaded NLC-PG and therefore may be useful for improving the bioavailability of curcumin.

Curcumin-loaded nanostructured lipid carriers prepared using Peceol™ and olive oil in photodynamic therapy: development and application in breast cancer cell line.

PurposeTo potentiate the anticancer activity of curcumin (CUR) by improving its cell penetration potentials through formulating it into nanostructured lipid carriers (NLCs) and using the prepared NLCs in photodynamic therapy.MethodsA 3×4 factorial design was used to obtain 12 CUR-NLCs using two factors on different levels: (1) the solid lipid type at four levels and (2) the solid to liquid lipid ratio at three levels. Olive oil, Tween 80 and lecithin were chosen as liquid lipid, surfactant and co-surfactant, respectively. CUR-NLCs prepared by high shear hot homogenization method were evaluated by determination of particle size (PS), polydispersity index, zeta potential (ZP), entrapment efficiency percent, drug loading percent and in vitro drug release. Optimization was based on the evaluation results using response surface modeling (RSM). Optimized formulae were tested for their in vitro release pattern and for dark and photo-cytotoxic anticancer activity on breast cancer cell line in comparison to free CUR.ResultsEvaluation tests showed the appropriateness of NLCs prepared from glyceryl monooleate and Geleol™ helped choosing two optimized formulae, PE3 and GE3. PE3 (prepared using glyceryl monooleate) showed enhanced release rates compared to GE3 (prepared from Geleol) and superior cytotoxic anticancer activity compared to both GE3 and free CUR under both light and dark conditions. The small mean PS, spherical shape as well as the negative ZP enhanced the internalization of the NLCs within cells. Modulation and inhibition of P-glycoprotein expression by glyceryl monooleate synergized the cytotoxic activity of CUR.ConclusionCUR loading in NLCs enhanced its cell penetration and cytotoxic anticancer properties both in dark and in light conditions.

Neuroprotective Potential of Curcumin-Loaded Nanostructured Lipid Carrier in an Animal Model of Alzheimer's Disease: Behavioral and Biochemical Evidence.

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and is caused by accumulation of amyloid-β (Aβ) peptide and is associated with neurological abnormalities in learning and memory. The protective role of curcumin on nerve cells, along with a potent antioxidant and free radical scavenging activity, has been widely studied. However, its low bioavailability and limited transport ability across the blood-brain barrier are two major drawbacks of its application in the treatment of different neurodegenerative diseases. The present study was designed to improve the effectiveness of curcumin in the treatment of Aβ-induced cognitive deficiencies in a rat model of AD by loading it into nanostructured lipid carriers (NLCs). The accumulation rate of curcumin (505.76±38.4 ng/g-1 h) in rat brain, as well as its serum levels, were significantly increased by using curcumin-loaded NLCs. The effective role of NLCs for brain delivery of curcumin was confirmed by reduced oxidative stress parameters (ROS formation, lipid peroxidation, and ADP/ATP ratio) in the hippocampal tissue and improvement of spatial memory. Also, histopathological studies revealed the potential of Cur-NLCs in decreasing the hallmarks of Aβ in AD in the animal model. The result of studying the neuroprotective potential of Cur-NLC in both pre-treatment and treatment modes showed that loading curcumin in NLCs is an effective strategy for increasing curcumin delivery to the brain and reducing Aβ-induced neurological abnormalities and memory defects and that it can be the basis for further studies in the area of AD prevention and treatment.

Curcumin-loaded Nanostructured Lipid Carriers for ocular drug delivery: Design optimization and characterization

The current study sought to formulate, optimize, and evaluate curcumin-loaded Nanostructured Lipid Carriers (NLCs) for their in vitro and ex vivo characteristics. NLCs, prepared using hot-melt emulsification and ultrasonication techniques, were optimized using a Central Composite Design (CCD) and evaluated for their in vitro physicochemical characteristics. Their stability over a 3 month period and transcorneal permeation across excised rabbit corneas (ex vivo) were assessed for the optimized NLCs. The optimized NLC, with a particle size of 66.8 ± 2 nm, polydispersity index of 0.17 ± 0.05, entrapment efficiency of 96 ± 1.6%, and drug loading of 3.1 ± 0.05% w/w, was chosen using CCD. The optimized NLCs showed optimum ex vivo stability at 4 °C for the study period and demonstrated a significant increase in curcumin permeation (∼2.5-fold) across the rabbit cornea in comparison to the control. Overall, these studies indicated the successful development of NLCs using the design of experiment approach; the formulation enhanced curcumin permeation across excised corneas and did not show any harmful side effects.

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

In order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax), mean residence time (MRT) and total plasma clearance (CLz/F). Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC50 value of 5.66 vs. 9.81 mg L-1, respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.