Curcumin-loaded Solid Lipid Nanoparticles Research Articles

Design and Evaluation of SLNs Encapsulated Curcumin-based Topical Formulation for the Management of Cervical Cancer.

Curcumin has the propensity to inhibit cancer growth, slow cancer development, increase chemotherapy effectiveness, and shield healthy cells from radiation treatment harm. As a result of curcumin's ability to block several signaling pathways, cervical cancer cells can once again proliferate normally. To optimize topically applied curcumin-loaded solid lipid nanoparticles (SLNPs) for the treatment of cervical cancer, this study set out to establish the relationship between design variables and experimental data. It also performed in vitro characterizations to determine the formulation's efficacy and safety. Curcumin-loaded SLNPs were constructed and optimized using a systematic design of experiment (DoE) technique. SLNPs that were loaded with curcumin were produced utilizing a cold emulsification ultrasonication process. Using the Box Behnken Design, it was determined how independent variables (factors) like the quantity of lipid (A), the quantity of phospholipid (B), and the concentration of surfactant (C) affected the responses of the dependent variables (responses), such as particle size (Y1), polydispersity index (PDI) (Y2), and entrapment efficiency (EE) (Y3) (BBD). The ideal formulation (SLN9) was chosen using the desirability technique based on 3-D surface response graphs. Using polynomial equations and three-dimensional surface plots, the influence of independent factors on the dependent variables was evaluated. The observed responses were almost equal to the levels that the optimal formulation expected. The improved SLNP gel's shape and other physicochemical characteristics were also assessed, and they were determined to be ideal. The sustained release profile of the produced formulations was validated by in vitro release tests. Studies on hemolysis, immunogenic response, and in vitro cell cytotoxicity demonstrate the efficacy and safety of the formulations. To improve the treatment effect, chitosan-coated SLNPs may carry encapsulated curcumin to the desired location and facilitate its localization and deposition in the desired vaginal tissue.

GelMA hydrogel scaffold containing curcumin-loaded solid lipid nanoparticles promotes the regeneration of degenerative discs

Intervertebral disc degenerative disease (IDD), which usually causes lower back and neck pain, is one of the most widespread musculoskeletal disorders and often causes a low quality of life. However, the surgical and conservative treatments commonly used in clinical practice are not effective. Previous studies have identified curcumin (Cur) as a potential therapeutic agent. However, its development in this regard has been limited due to its low dissolution, instability in water, and rapid metabolism. In this study, we developed a novel anti-inflammatory composite hydrogel scaffold with curcumin encapsulated in solid lipid nanoparticles and mixed it with gelatin methacrylate (GelMA) hydrogel to treat IDD. The hydrogel scaffold, denoted Cur-solid lipid nanoparticles (SLNs)/GelMA, promoted the restoration of Collagen type II (Col II) and aggrecan expression levels in vivo, indicating that the regeneration of the intervertebral discs was effective. Combined in vitro studies showed that Cur-SLNs inhibited the expression of the inflammatory factors TNF-α and IL-6. Additionally, immunofluorescence and western blotting experiments verified that Cur-SLNs regulated the recovery of Col II and aggrecan in an inflammatory environment and promoted the metabolic homeostasis of the extramedullary cell matrix. In conclusion, this study provides a new strategy to promote IDD regeneration, which brings new application prospects.

Physicochemical Characterization, Stability, and In Vitro Evaluation of Curcumin-Loaded Solid Lipid Nanoparticles Prepared Using Biocompatible Synthetic Lipids.

Solid lipid nanoparticles (SLNs) are promising drug delivery vehicles for the delivery of various drugs, especially poorly water-soluble drugs. However, the aqueous stability, drug release, and biocompatibility of SLNs are some of the issues that need attention. In this work, curcumin-loaded SLNs were prepared, and morphology, particle size, and entrapment efficiency were studied. For this, two amino acid-derived lipids were developed. The effect of the polarity of the lipid head on the aqueous stability of the SLN dispersion was investigated. Based on the stability, particle size, and polydispersity, an optimum formulation was obtained. The curcumin entrapment efficiency of the SLNs was found to be greater than those reported in the literature. The entrapped curcumin, as well as curcumin-loaded SLN suspensions, exhibited improved storage stability. The in vitro release kinetics indicated an enhanced rate of drug release in the case of curcumin-loaded SLNs consisting of the lipid containing -OH groups at the lipid head. The pure lipid and the blank SLN were found to have no significant cytotoxicity, but curcumin and curcumin-loaded SLNs induced cell death in a concentration-dependent manner in both human prostatic adenocarcinoma PC3 cell line and human breast carcinoma MCF7 cell line. This study has proposed a potential semisynthetic lipid for the stable SLN suspension for the delivery of curcumin.

Nanocurcumin and viable Lactobacillus plantarum based sponge dressing for skin wound healing

Curcumin loaded solid lipid nanoparticles (CSLNs) and probiotic (Lactobacillus plantarum UBLP-40; L. plantarum) were currently co-incorporated into a wound dressing. The combination with manifold anti-inflammatory, anti-infective, analgesic, and antioxidant properties of both curcumin and L. plantarum will better manage complex healing process. Recent reports indicate that polyphenolics like curcumin improve probiotic effects. Curcumin was nanoencapsulated (CSLNs) to improve its bioprofile and achieve controlled release on the wound bed. Bacteriotherapy (probiotic) is established to promote wound healing via antimicrobial activity, inhibition of pathogenic toxins, immunomodulation, and anti-inflammatory actions. Combination of CSLNs with probiotic enhanced (560%) its antimicrobial effects against planktonic cells and biofilms of skin pathogen, Staphylococcus aureus 9144. The sterile dressing was devised with selected polymers, and optimized for polymer concentration, and dressing characteristics using a central composite design. It exhibited a swelling ratio of 412 ± 36%, in vitro degradation time of 3 h, optimal water vapor transmission rate of 1516.81 ± 155.25 g/m2/day, high tensile strength, low-blood clotting index, case II transport, and controlled release of curcumin. XRD indicated strong interaction between employed polymers. FESEM revealed a porous sponge like meshwork embedded with L. plantarum and CSLNs. It degraded and released L. plantarum, which germinated in the wound bed. The sponge was stable under refrigerated conditions for up to six months. No translocation of probiotic from wound to the internal organs confirmed safety. The dressing exhibited faster wound closure and lowered bioburden in the wound area in mice. This was coupled with a decrease in TNF-α, MMP-9, and LPO levels; and an increase in VEGF, TGF-β, and antioxidant enzymes such as catalase and GSH, establishing multiple healing pathways. Results were compared with CSLNs and probiotic-alone dressings. The dressing was as effective as the silver nanoparticle-based marketed hydrogel dressing; however, the cost and risk of developing resistance would be much lower currently.

Physicochemical and In Vitro Digestion Properties of Curcumin-Loaded Solid Lipid Nanoparticles with Different Solid Lipids and Emulsifiers.

Curcumin-loaded solid lipid nanoparticles (Cur-SLN) were prepared using medium- and long chain diacylglycerol (MLCD) or glycerol tripalmitate (TP) as lipid matrix and three kinds of surfactants including Tween 20 (T20), quillaja saponin (SQ) and rhamnolipid (Rha). The MLCD-based SLNs had a smaller size and lower surface charge than TP-SLNs with a Cur encapsulation efficiency of 87.54-95.32% and the Rha-based SLNs exhibited a small size but low stability to pH decreases and ionic strength. Thermal analysis and X-ray diffraction results confirmed that the SLNs with different lipid cores showed varying structures, melting and crystallization profiles. The emulsifiers slightly impacted the crystal polymorphism of MLCD-SLNs but largely influenced that of TP-SLNs. Meanwhile, the polymorphism transition was less significant for MLCD-SLNs, which accounted for the better stabilization of particle size and higher encapsulation efficiency of MLCD-SLNs during storage. In vitro studies showed that emulsifier formulation greatly impacted on the Cur bioavailability, whereby T20-SLNs showed much higher digestibility and bioavailability than that of SQ- and Rha-SLNs possibly due to the difference in the interfacial composition. Mathematical modeling analysis of the membrane release further confirmed that Cur was mainly released from the intestinal phase and T20-SLNs showed a faster release rate compared with other formulations. This work contributes to a better understanding of the performance of MLCD in lipophilic compound-loaded SLNs and has important implications for the rational design of lipid nanocarriers and in instructing their application in functional food products.

Fabrication of Sustained Release Curcumin-Loaded Solid Lipid Nanoparticles (Cur-SLNs) as a Potential Drug Delivery System for the Treatment of Lung Cancer: Optimization of Formulation and In Vitro Biological Evaluation.

The goal of current research was to develop a new form of effective drug, curcumin-loaded solid lipid nanoparticles (Cur-SLNs) and test its efficacy in the treatment of lung cancer. Different batches of SLNs were prepared by the emulsification-ultrasonication method. For the optimization of formulation, each batch was evaluated for particle size, polydispersity index (PI), zeta potential (ZP), entrapment efficiency (EE) and drug loading (DL). The formulation components and process parameters largely affected the quality of SLNs. The SLNs obtained with particle size, 114.9 ± 1.36 nm; PI, 0.112 ± 0.005; ZP, -32.3 ± 0.30 mV; EE, 69.74 ± 2.03%, and DL, 0.81 ± 0.04% was designated as an optimized formulation. The formulation was freeze-dried to remove excess water to improve the physical stability. Freeze-dried Cur-SLNs showed 99.32% of drug release and demonstrated a burst effect trailed by sustained release up to 120 h periods. The erythrocyte toxicity study of Cur-SLNs and its components demonstrated moderate hemolytic potential towards red blood cells (RBCs). The cytotoxic potential of the formulation and plain curcumin was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against A549 cell line. After 48 h of incubation, Cur-SLNs demonstrated more cytotoxicity (IC50 = 26.12 ± 1.24 µM) than plain curcumin (IC50 = 35.12 ± 2.33 µM). Moreover, the cellular uptake of curcumin was found to be significantly higher from Cur-SLNs (682.08 ± 6.33 ng/µg) compared to plain curcumin (162.4 ± 4.2 ng/µg). Additionally, the optimized formulation was found to be stable over the period of 90 days of storage. Hence, curcumin-loaded SLNs can be prepared using the proposed cost effective method, and can be utilized as an effective drug delivery system for the treatment of lung cancer, provided in vivo studies warrant a similar outcome.

Incorporation of Solid Lipid Nanoparticles into Stirred Yogurt: Effects in Physicochemical and Rheological Properties during Shelf-Life

The aim of this work was to develop a yogurt fortified with curcumin. Curcumin is a lipophilic compound with a wide range of biological activities; however, it presents low water solubility and low bioavailability, and therefore it was the first to be encapsulated in solid lipid nanoparticles (SLNs). Then the influence of the incorporation of curcumin-loaded SLNs on the physicochemical (i.e., pH, titratable acidity, syneresis and color) and rheological properties of yogurt during its shelf-life (30 days at 4 °C) was evaluated. SLN incorporation into yogurt did not affect pH and titratable acidity compared to the control (i.e., plain yogurt) during shelf-life, even though the yogurt with SLNs presented lower values of pH (4.25 and 4.34) and acidity (0.74% lactic acid and 0.84% lactic acid) than the control in the end, respectively. Furthermore, the yogurt with SLNs presented slightly higher values of syneresis than the control during the shelf-life; however, it did not present visual differences in whey separation. Relative to the color, the incorporation of SLNs into the yogurt imparted a strong yellow color to the sample but did not affect color stability during shelf-life. Both samples showed flow curves with yield stress and shear-thinning behavior during shelf-life, and, regarding the viscoelastic behavior, both showed a typical weak viscoelastic gel with an elastic structure. Overall, curcumin-loaded SLNs incorporation did not affect the physicochemical and rheological stability of yogurt during shelf-life, showing a promising application for the development of new functional foods.

Optimization and Fabrication of Curcumin Loaded Solid Lipid Nanoparticles Using Box-Behnken Design for Nasal Delivery

Aims: To prepare curcumin loaded solid lipid nanoparticles for nasal administration using Box-Behnken design. Background: The effectiveness of curcumin in neurological disorders is widely studied by various researchers, but its use is limited due to its poor bioavailability. The brain-targeting efficiency of curcumin can be improved using solid lipid nanoparticles via nasal administration. Objective: In the present work, Curcumin loaded solid lipid nanoparticles (CUR-SLN) were formulated and optimized for nasal administration. Methods: Based on solubility studies, cetostearyl alcohol and poloxamer 407 were selected as lipid and surfactant, respectively. Box-Behnken design (BBD) was used to analyze the effects of drug-to-lipid ratio (X1), surfactant concentration (X2) and homogenization time (X3) on particle size (Y1) and % entrapment efficiency (Y2). The CUR-SLN were formulated by the high shear homogenization method. The optimized formulation was evaluated for DSC, TEM, drug release and ex-vivo studies. Results: Good results were obtained for the particle size and entrapment efficiency analyzed using BBD. The optimized formulation of CUR-SLN obtained using BBD was observed with a particle size of 96.09 nm and % EE of 78.23. In-vitro release of the drug was found to be 82.93± 0.15% after 8 hours. DSC studies revealed that crystalline form of curcumin changed to an amorphous form in SLN. TEM results of optimized CUR-SLN were in correlation with the results obtained using a zeta sizer. No harmful effects were observed on nasal mucosa in the histopathology study. Conclusion: The SLN can be safely utilized for the intranasal administration of curcumin.

Effect of Unloaded and Curcumin-Loaded Solid Lipid Nanoparticles on Tissue Transglutaminase Isoforms Expression Levels in an Experimental Model of Alzheimer's Disease.

Alzheimer’s disease (AD) is a neurodegenerative disease representing the most prevalent cause of dementia. It is also related to the aberrant amyloid-beta (Aβ) protein deposition in the brain. Since oxidative stress is involved in AD, there is a possible role of antioxidants present in the effected person’s diet. Thus, we assessed the effect of the systemic administration of solid lipid nanoparticles (SLNs) to facilitate curcumin (CUR) delivery on TG2 isoform expression levels in Wild Type (WT) and in TgCRND8 (Tg) mice. An experimental model of AD, which expresses two mutated human amyloid precursor protein (APP) genes, was used. Behavioral studies were also performed to evaluate the improvement of cognitive performance and memory function induced by all treatments. The expression levels of Bcl-2, Cyclin-D1, and caspase-3 cleavage were evaluated as well. In this research, for the first time, we demonstrated that the systemic administration of SLNs-CUR, both in WT and in Tg mice, allows one to differently modulate TG2 isoforms, which act either on apoptotic pathway activation or on the ability of the protein to repair cellular damage in the brains of Tg mice. In this study, we also suggest that SLNs-CUR could be an innovative tool for the treatment of AD.

Evaluation of the hepatoprotective effect of curcumin-loaded solid lipid nanoparticles against paracetamol overdose toxicity: Role of inducible nitric oxide synthase

Curcumin (Cur) is a natural compound that exhibited therapeutic effects against various liver injuries however Cur showed poor water solubility and bioavailability. This study aimed to design Cur-loaded solid lipid nanoparticles (SLNs) and to evaluate the hepatoprotective and antioxidant effects in a model of acute hepatotoxicity induced by paracetamol (PCM) overdose compared to the raw Cur and N-acetylcysteine (NAC). SLNs were prepared by emulsion/solvent evaporation method and 32 factorial design was employed. Wistar rats were divided into Control, PCM, PCM + NAC, PCM + raw Cur, and PCM + Cur-SLNs groups and treated orally for 14 days before receiving a single PCM dose. The Cur-loaded SLNs showed high entrapment efficiency % ranging between 69.1 and 92.1%, particle size (PS) between 217 and 506 nm, and zeta potential values between −17.9 and −25.5 mV. The in vivo results revealed that the PCM group exhibited deterioration of liver functions, pathological lesions on the liver tissues, severe oxidative stress, and increases in both the serum and hepatic iNOS levels. Remarkably, the PCM + Cur-SLNs group showed significantly better liver functions and tissue integrity compared to the PCM group. Furthermore, higher reduced glutathione and catalase but lower malondialdehyde and iNOS levels were observed. In conclusion, Cur-loaded SLNs effectively prevented the liver damage induced by PCM overdose through alleviating the oxidative stress and inhibiting the serum and hepatic iNOS expression in an effect comparable to NAC and better than raw Cur.

Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study.

Curcumin is well known for its neuroprotective effect, and also able to alleviate Parkinsonian features. Clinical application of curcumin is limited due to its low bioavailability. Hence, we hypothesized that the microneedles (MN) containing drug-loaded solid lipid nanoparticles (SLNs) may be able to improve its bioavailability and efficacy. The SLNs were prepared with microemulsion technique using glyceryl monostearate as a lipid and tween 80 as a stabilizer. The particle size, polydispersity index, zeta potential, and entrapment efficiency of prepared SLNs were determined. The optimized formulation was incorporated into microneedle arrays using micromolding technique and fabricated microneedle patch were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, optical microscopy, ex vivo permeation studies, histology studies, and fluorescent microscopy. The fabricated microneedle patch was also evaluated for neuroprotective activity and skin irritation potential. Fourier transform infrared spectroscopy studies of SLNs and microneedles confirmed the chemical compatibility of excipients with curcumin. The developed microneedles were also found to be non-irritant with decreased degree of bradykinesia, high motor coordination, and balance ability. The study provided a theoretical basis for the use of novel microneedle containing curcumin-loaded solid lipid nanoparticles as a useful tool for the treatment of Parkinson's disease.

Neuroprotective effects of curcumin loaded solid lipid nanoparticles on homocysteine induced oxidative stress in vascular dementia

Vascular dementia (VaD), a diverse group of brain disorders with cognitive decline is attributable to cerebrovascular pathologies. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. Several studies consider that oxidative stress is the main pathogenic factor in VaD. However, curcumin is having a therapeutic potential in oxidative stress and is limited due to its compromised bioavailability (BA). The current study aims to evaluate the neuroprotective effects of curcumin loaded solid lipid nanoparticles (Cur-SLNP) on homocysteine (HCY) induced oxidative stress in vascular dementia (VaD) by behavioural, biochemical, neurochemical, and histopathological alterations in different regions of the brain. Male sprague dawley rats were divided in to six groups. Group I was normal control and group II received HCY at 400 µg/kg/day, i.v for 14 days. Group III and IV received (Cur – 25 mg/kg, p.o + HCY- 400 µg/kg/day, i.v) and (Cur – 50 mg/kg, p.o + HCY- 400 µg/kg/day, i.v) . Group V and VI received Cur-SLNP at the dose (Cur – SLNP – 10 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) and (Cur – SLNP – 25 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) for 14 days. Subsequently, rats were tested for behavioral assessments on 0th, 7th, and 14th days and then sacrificed for biochemical, neurochemical, and histopathological assays in different regions of the brain. In the present study, the treatment with Cur-SLNP at high dose (Cur – SLNP – 25 mg/kg, p.o + HCY - 400 µg/kg/day, i.v) successfully ameliorated the oxidative stress in VaD by the estimations of biochemical, neurochemical and histological alterations. Thus, Cur-SLNP at high dose can be considered as a potential therapeutic strategy for the treatment of oxidative stress in vascular dementia induced by homocysteine in different regions of the brain. To the best of our knowledge, based on the results, this is the first study to reveal the neuroprotective effects of Cur-SLNP on HCY induced oxidative stress in vascular dementia.

Curcumin loaded Solid lipid nanoparticles enhanced efficacy in vascular dementia against Homocysteine induced toxicity

Vascular dementia (VaD), a diverse group of brain disorders with cognitive decline is attributable to cerebrovascular pathologies. Recent studies have shown that mitochondrial dysfunctions and oxidative stress are involved in cognitive decline. The aim of the present study was designed to evaluate the effects of Curcumin loaded solid lipid nanoparticles (Cur-SLNP) in vascular dementia (VaD) against homocystiene (HCY) induced toxicity by behavioral and biochemical assessment in different regions of the brain. The sign of VaD i.e., learning and memory levels were evaluated with different behavioural assessment like plus maze test. Neurobehavioral analyses revealed that Cur-SLNP administration successfully ameliorated cognitive decline observed in HCY rats. Compared to HCY administration, Cur-SLNP 10 mg/kg and 25 mg/kg administration showed ameliorative effect in behavioural and biochemical assessment induced by HCY. We found that lipid peroxidation levels decreased significantly in striatum (p<0.01), cortex (p<0.001), and hippocampus (p<0.001) after oral administration of Cur-SLNP with HCY animals. Hence, the present findings suggest that the neuroprotective role of Cur-SLNP against HCY induced toxicity could be a novel and promising therapeutic strategy in VaD as well in other age-related neurodegenerative disorders.

Pharmacokinetics and Pharmacodynamics of Curcumin-Loaded Solid Lipid Nanoparticles in the Management of Streptozotocin-Induced Diabetes Mellitus: Application of Central Composite Design

Due to poor bioavailability and chemical instability, the effectiveness of curcumin is negligible in the treatment of numerous diseases. Solid lipid nanoparticles (SLNs) increase the bioavailability of lipophilic compounds and protect the drug from gastrointestinal degradation. The objective of our study is the utilization of SLNs to improve the pharmacokinetics and pharmacodynamics of curcumin in the management of diabetes mellitus. Central composite design was used to prepare curcumin-loaded SLNs (Cur-SLN). The analysis of independent variables like drug concentration, lipid concentration, and surfactant concentration was carried out using analysis of variance (ANOVA) to obtain the optimized batch (optimized Cur-SLN) having the desired values of dependent variables particle size and entrapment efficiency. In vitro release, differential scanning calorimeter (DSC), transmission electron microscopy (TEM), and Fourier Transform Infra-Red (FTIR) studies of optimized Cur-SLN were carried out and then its pharmacokinetic and pharmacodynamic studies were performed. The model was found to be significant for particle size and entrapment efficiency based on F-value and p-value. The optimized batch's predicted values were in close agreement with the actual values of particle size and entrapment efficiency. TEM results confirm mono-dispersion and spherical shape of particles in the formulation. The DSC results confirmed the changing of drug from crystalline to amorphous form. Burst release followed by the sustained release was obtained in the in vitro release studies. The pharmacokinetic study shows enhanced bioavailability of optimized Cur-SLN compared with a plain drug suspension. The optimized Cur-SLN achieved higher antidiabetic activity in streptozotocin-induced diabetes mellitus rats than the plain drug suspension. SLNs can be used as a promising technique for delivering curcumin in the management of diabetes mellitus.

An efficient approach for development and optimisation of curcumin-loaded solid lipid nanoparticles’ patch for transdermal delivery

This study aimed to develop and optimise a Curcumin-loaded SLNs (C-SLNs) patch through a new approach for transdermal delivery. C-SLNs were optimised through the response surface central composite design using the modified injection method. Optimised C-SLNs were loaded into a polyvinyl alcohol-based patch through the backing membrane method. Compatibility studies (FTIR, XRPD), in vitro release, ex vivo skin permeation, accelerated stability, and evaluation studies of the patch were also performed. Prepared C-SLNs exhibited average particle diameter of 170 ± 2 nm with an encapsulation efficiency of 90 ± 3.5% (w/w) while SEM illustrated spherical shape of particles. In vitro release data ensured a sustained release for up to 72 hours. The enhancement ratio of C-SLNs based patch with permeation enhancer (PE) was high up to 6.5 folds as compared to patch without PE. It is concluded that the modified injection method is simple, economical, and less time consuming for the development of C-SLNs patch for the transdermal route.

Emerging nanomaterials applied for tackling the COVID-19 cytokine storm.

During the global outbreak of coronavirus disease 2019 (COVID-19), a hyperinflammatory state called the cytokine storm was recognized as a major contributor to multiple organ failure and mortality. However, to date, the diagnosis and treatment of the cytokine storm remain major challenges for the clinical prognosis of COVID-19. In this review, we outline various nanomaterial-based strategies for preventing the COVID-19 cytokine storm. We highlight the contribution of nanomaterials to directly inhibit cytokine release. We then discuss how nanomaterials can be used to deliver anti-inflammatory drugs to calm the cytokine storm. Nanomaterials also play crucial roles in diagnostics. Nanomaterial-based biosensors with improved sensitivity and specificity can be used to detect cytokines. In summary, emerging nanomaterials offer platforms and tools for the detection and treatment of the COVID-19 cytokine storm and future pandemic.

Antineuroinflammatory Activities and Neurotoxicological Assessment of Curcumin Loaded Solid Lipid Nanoparticles on LPS-Stimulated BV-2 Microglia Cell Models.

Curcumin, which is a potential antineuroinflammatory and neuroprotective compound, exhibits poor bioavailability in brain cells due to its difficulty in crossing the blood–brain barrier and its rapid metabolism during circulation, which decreases its efficacy in treating chronic neuroinflammatory diseases in the central nervous system. The bioavailability and potential of curcumin can be improved by using a nanodelivery system, which includes solid lipid nanoparticles. Curcumin-loaded solid lipid nanoparticles (SLCN) were efficiently developed to have a particle size of about 86 nm and do not exhibit any toxicity in the endothelial brain cells. Furthermore, the curcumin-loaded solid lipid nanoparticles (SLCN) were studied to assess their efficacy in BV-2 microglial cells against LPS-induced neuroinflammation. The SLCN showed a higher inhibition of nitric oxide (NO) production compared to conventional curcumin in a dose-dependent manner. Similarly, the mRNA and proinflammatory cytokine levels were also reduced in a dose-dependent manner when compared to those with free curcumin. Thus, SLCN could be a potential delivery system for curcumin to treat microglia-mediated neuroinflammation.

Brain Delivery of Curcumin Using Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Preparation, Optimization, and Pharmacokinetic Evaluation.

Curcumin is a multitherapeutic agent with great therapeutic potential in central nervous system (CNS) diseases. In the current study, curcumin was encapsulated in solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the purpose of increasing brain accumulation. The preparation processes have been optimized using experimental design and multiobjective optimization methods. Entrapment efficiency of curcumin in SLNs and NLCs was found to be 82% ± 0.49 and 94% ± 0.74, respectively. The pharmacokinetic studies showed that the amount of curcumin available in the brain was significantly higher in curcumin-loaded NLCs (AUC0-t = 505.76 ng/g h) compared to free curcumin (AUC0-t = 0.00 ng/g h) and curcumin-loaded SLNs (AUC0-t = 116.31 ng/g h) ( P < 0.005), after intravenous (IV) administration of 4 mg/kg dose of curcumin in rat. The results of differential scanning calorimetry and X-ray diffraction showed that curcumin has been dispersed as amorphous in the nanocarriers. Scanning electron microscopy images confirmed the nanoscale size and spherical shape of the nanoparticles. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging study indicated that preparation processes do not have any significant effect on the antioxidant activity of curcumin. The results of this study are promising for the use of curcumin-loaded NLCs in more studies and using curcumin in the treatment of CNS diseases.

Development of Curcumin-Loaded Solid Lipid Nanoparticles Utilizing Glyceryl Monostearate as Single Lipid Using QbD Approach: Characterization and Evaluation of Anticancer Activity Against Human Breast Cancer Cell Line.

Solid lipid nanoparticles (SLNs) represent an affordable, easily scalable, stable and biocompatible drug delivery system with a high drug to lipid ratio which also improves solubility of poorly soluble drugs. SLNs were developed by using glyceryl monostearate as the single lipid in the presence of surfactant Poloxamer 188 and evaluated the efficiency of SLNs to load the therapeutic cargo, curcumin (CUR). The nano-formulation was optimized by Quality by Design approach to understand the effect of various process parameters on various quality attributes, including drug loadability, particle size and polydispersity. The nanoparticles were characterized using Differential scanning calorimetry (DSC), Fourier Transform Infra-red Spectroscopy (FT-IR) and X-Ray Diffraction (XRD) analysis. These novel SLNs were evaluated for in-vitro anticancer activity using breast adenocarcinoma cells (MDA-MB-231). The optimized formulation had a particle size of 226.802±3.92 nm with low polydispersity index of 0.244±0.018. The % encapsulation of CUR into SLNs was found to be 67.88±2.08 %. DSC, FT-IR and XRD confirmed that the CUR was encapsulated stably into the lipid matrix, thereby improving the solubility of the drug. CUR-SLN showed sustained drug release in comparison to the free CUR solution. CUR-SLNs exhibited higher cellular uptake in human breast adenocarcinoma cells compared to free CUR at both 1 and 4 h time points. CUR-SLNs demonstrated decreased cell viability (43.97±1.53%) compared to free CUR (59.33±0.95%) at a concentration of 50 µg/mL after 24 h treatment. Furthermore, the treatment of MDA-MB-231 cells with CUR-SLNs for 24 h induced significantly higher apoptosis (37.28±5.3%) in cells compared to the free CUR (21.06±0.97%). The results provide a strong rationale for further exploration of the newly developed CUR-SLN to be utilized as a potent chemotherapeutic agent in cancer therapy.

Curcumin-Loaded Solid Lipid Nanoparticles Enhanced Anticancer Efficiency in Breast Cancer.

Curcumin (Cur) has been widely used in medicine, due to its antibacterial, anti-inflammatory, antioxidant, and antitumor effects. However, its clinic application is limited by its instability and poor solubility. In the present wok, curcumin was loaded into solid lipid nanoparticles (SLNs), in order to improve the therapeutic efficacy for breast cancer. The results measured using transmission electron microscopy (TEM) indicated that Cur-SLNs have a well-defined spherical shape; the size was about 40 nm with a negative surface charge. The drug loading and encapsulation efficiency in SLNs reached 23.38% and 72.47%, respectively. The Cur-SLNs showed a stronger cytotoxicity against SKBR3 cells. In vitro cellular uptake study demonstrated a high uptake efficiency of the Cur-SLNs by SKBR3 cells. Moreover, Cur-SLNs induced higher apoptosis in SKBR3 cells, compared to cells treated by free drug. In addition, Western blot analysis revealed that Cur-SLNs could promote the ratio of Bax/Bcl-2, but decreased the expression of cyclin D1 and CDK4. These results suggested that Cur-SLNs could be a potential useful chemotherapeutic formulation for breast cancer therapy.