Novel Biphasic In Vitro Dissolution Method Correctly Predicts the Oral Bioavailability of Curcumin in Humans.

In vitro dissolution methods correctly predicting in vivo bioavailability of compounds from complex mixtures are lacking. We therefore used data on the in vivo performance of bioavailability-improved curcumin formulations to implement an in vivo predictive dissolution method (BiPHa+). BiPHa+ was applied for the characterization of eight curcumin formulations previously studied in a strictly controlled pharmacokinetic human trial. During dissolution, the dissolved proportion of curcumin in the aqueous medium underwent a formulation-dependent reduction, whereas the proportion remained stable in the organic layer. Compared with conventional dissolution systems, BiPHa+ was superior in terms of in vivo-relevant formulation characterization. All formulations could be precisely categorized according to their bioavailability in humans. In vitro-in vivo relationships for each dissolution method were established, with BiPHa+ providing the highest degree of linearity (r2 = 0.9975). The BiPHa+ assay correctly predicted the bioavailability of curcuminoids from complex mixtures and provided mechanistic information about formulation-dependent release characteristics.

Enhanced Pharmacokinetics and Anti-inflammatory Activity of Curcumin Using Dry Emulsion as Drug Delivery Vehicle.

BACKGROUND AND OBJECTIVE: Many naturally available dietary molecules such as curcumin have not seen the market due to poor solubility, bioavailability, and photodegradability. Successful development of a lipid-based dry emulsion may overcome these issues and help in reaching the markets for natural dietary molecules such as curcumin. The current study aims to develop a dry emulsion formulation of curcumin using natural oil and evaluate its dissolution, photostability, pharmacokinetics, and anti-inflammatory activity. METHODS: Dry emulsions were prepared using emu oil and corn oil as the lipid phase, Caproyl 90 and Cremophor RH 40 as surfactants, and dextrin as a hydrophilic carrier. RESULTS: Microscopic studies showed the formation of spherical porous particles, and solid-state characterization using differential scanning calorimetry and powder X-ray diffraction showed the conversion of curcumin to an amorphous form. About 80% drug release was observed from formulation, whereas pure drug showed only 50% drug release in 30 min. In vivo pharmacokinetic studies showed fivefold improvement in the maximum concentration of curcumin in plasma (Cmax) and sevenfold improvement in the area under the concentration-time curve of curcumin from emu oil formulation compared with pure curcumin. Significant differences were observed in the anti-inflammatory activity of curcumin dry emulsion and plain curcumin. Emu-oil-based formulations showed synergistic anti-inflammatory activity over corn-oil-based formulations with improved photostability. CONCLUSION: The present study suggests that the dry emulsion may enhance the bioavailability with synergistic anti-inflammatory activity and photostability of curcumin when given orally.

Regional distributions of curcumin and tetrahydrocurcumin in the liver and small intestine of rats when orally co-administered with quercetin and paeoniflorin.

Curcumin (CUR), derived from the dietary spice turmeric, is a polyphenolic compound with various biological and pharmacological activities. Tetrahydrocurcumin (THC) is one of the major reductive metabolites of curcumin. A pharmacokinetic study using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) for the simultaneous determination of curcumin, THC, quercetin (QR), and paeoniflorin (PF) in rat plasma had been performed. In this study, the regional distributions of curcumin and tetrahydrocurcumin in the liver and the three segments of small intestine (duodenum, jejunum, and ileum) of rats when orally co-administered with quercetin and paeoniflorin were carried out. Drug concentrations were determined using UHPLC-MS/MS. The results showed that curcumin was well distributed in the small intestine, while the distributions of tetrahydrocurcumin in the liver, duodenum, jejunum were similar, but much more abundant in the ileum. When orally co-administered with quercetin and paeoniflorin, the tissue to plasma concentration ratios (Kp values) of curcumin in the three segments of the small intestine were increased, indicating that the presence of quercetin and paeoniflorin increases the distribution of curcumin in these regions. Moreover, the half-life (t1/2 ) of THC in the liver was significantly prolonged, and the Kp value of THC in the liver was increased and the Kp values in the small intestine were decreased, suggesting that the combination of quercetin and paeoniflorin might suppress the metabolism of curcumin in the small intestine. In brief, the combination had an effect on the distributions of curcumin and tetrahydrocurcumin in the liver and small intestine of rats.

Comparative Pharmacokinetic of Curcuminoids Formulations with an Omega-3 Fatty Acids Monoglyceride Carrier: A Randomized Cross-Over Triple-Blind Study.

There is a growing interest for curcuminoids in the general population and the scientific research community. Curcuminoids, derived from turmeric spice, are lipophiles and therefore have a low solubility in water which hence have a low bioavailability in the human plasma. To circumvent this issue, a natural product developed by Biodroga Nutraceuticals combined curcuminoids with omega-3 fatty acids (OM3) esterified in monoglycerides (MAG). The objective was to perform a 24 h pharmacokinetics in humans receiving a single dose of curcuminoid formulated by three different means, and to compare their plasma curcuminoids concentration. Sixteen males and fifteen females tested three formulations: 400 mg of curcuminoids powder extract, 400 mg of curcuminoids in rice oil and 400 mg of curcuminoids with 1 g MAG-OM3. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 8, 10 and 24 h post dose intake. Plasma samples were analyzed by ultra high-performance liquid chromatography with a triple quadrupole mass spectrometer (UPLC-MS/MS). Twenty-four hours after a single dose intake, the total plasma curcuminoids area under the curve (AUC) reached 166.8 ± 17.8 ng/mL*h, 134.0 ± 12.7 ng/mL*h and 163.1 ± 15.3 ng/mL*h when curcuminoids were provided with MAG-OM3, with rice oil or in powder, respectively. The Cmax of total curcuminoids reached between 11.9-17.7 ng/mL at around 4 h (Tmax). One-hour post-dose, the curcuminoids plasma concentration was 40% higher in participants consuming the MAG-OM3 compared to the other formulations. Thus, in a young population, plasma curcuminoids 24 h pharmacokinetics and its increase shortly after the single dose intake were higher when provided with MAG-OM3 than rice oil.

Pharmacokinetics of a single dose of novel curcumin formulations mixed with fish oils in healthy humans.

The pharmacokinetics of novel formulations of curcumin mixed with squalene (CSQU) and of curcumin mixed with docosahexaenoic acid (CDHA) was investigated and compared with a standardized unformulated curcumin extract (StdC) and a solid lipid curcumin particle (SLCP) formulation in a randomized, open-label, crossover study. A total of 10 healthy subjects consumed a single dose of each formulation, and blood samples were collected over 8 h. Plasma concentrations of curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) were measured. The dose-normalized AUC0-8h of curcumin was significantly higher for SLCP (2.2-fold), CSQU (2.3-fold) and CDHA (2.8-fold) than for StdC. The dose-normalized AUC0-8h of DMC and BDMC did not significantly change, but their Tmax was significantly shortened for SLCP, CSQU, and CDHA. In conclusion, compared with StdC, both fish oil formulations, CSQU and CDHA, significantly improved curcumin absorption as well as SLCP, and CDHA was bioequivalent or superior to SLCP. No sex differences were observed in curcumin absorption.

Comparative pharmacokinetics of new curcumin preparations and evidence for increased bioavailability in healthy adult participants.

OBJECTIVE: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted. MATERIALS AND METHODS: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) 0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of Cmax. TS-P1 tended to have a higher Cmax than CR-033P, CR-043P tended to have a slightly lower Cmax than CR-033P, and TS-P1 tended to have a higher Cmax than CR-043P. CONCLUSION: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

Effects of wound dressing based on the combination of silver@curcumin nanoparticles and electrospun chitosan nanofibers on wound healing.

Healing of various skin wounds is a lengthy process and often combined with bacterial infection and scar formation. Biomimetic electrospun nanofibrous wound dressing loaded with materials that possess properties of dual antibacterial and tissue repair would be developed to address this problem. In this study, a composite chitosan electrospun nanofibrous material containing Cur@ß-CD/AgNPs nanoparticles composed of silver and curcumin possessed synergic effects on antibacterial activity and wound healing. The developed functionalized silver nanoparticles showed effective activity against both Gram-negative and Gram-positive bacteria. In vivo, Cur@ß-CD/AgNPs chitosan dressing displayed enhanced wound closure rates compared to commercial AquacelAg. Moreover, Cur@ß-CD/AgNPs chitosan dressing contributed to the most uniform collagen distribution by Masson's trichrome staining. In brief, Cur@ß-CD/AgNPs chitosan nanofibers work as a potential wound dressing with antibacterial and antiscarring properties.

Nanocurcumin Potently Inhibits SARS-CoV-2 Spike Protein-Induced Cytokine Storm by Deactivation of MAPK/NF-κB Signaling in Epithelial Cells.

Interleukin-mediated deep cytokine storm, an aggressive inflammatory response to SARS-CoV-2 virus infection in COVID-19 patients, is correlated directly with lung injury, multi-organ failure, and poor prognosis of severe COVID-19 patients. Curcumin (CUR), a phenolic antioxidant compound obtained from turmeric (Curcuma longa L.), is well-known for its strong anti-inflammatory activity. However, its in vivo efficacy is constrained due to poor bioavailability. Herein, we report that CUR-encapsulated polysaccharide nanoparticles (CUR-PS-NPs) potently inhibit the release of cytokines, chemokines, and growth factors associated with damage of SARS-CoV-2 spike protein (CoV2-SP)-stimulated liver Huh7.5 and lung A549 epithelial cells. Treatment with CUR-PS-NPs effectively attenuated the interaction of ACE2 and CoV2-SP. The effects of CUR-PS-NPs were linked to reduced NF-κB/MAPK signaling which in turn decreased CoV2-SP-mediated phosphorylation of p38 MAPK, p42/44 MAPK, and p65/NF-κB as well as nuclear p65/NF-κB expression. The findings of the study strongly indicate that organic NPs of CUR can be used to control hyper-inflammatory responses and prevent lung and liver injuries associated with CoV2-SP-mediated cytokine storm.

Multilayered Curcumin-Loaded Hydrogel Microcarriers with Antimicrobial Function.

The design of multifunctional microcarriers has attracted significant attention because they combine various functions within a single system. In this study, we developed a set of multilayered hydrogel microcarriers, which were first loaded with chemotherapeutic curcumin (CUR), then, using the layer-by-layer (LbL) technique, coated through a polyelectrolyte shell consisting of chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). As an outer layer with antimicrobial function, newly synthesised alkylene quaternary ammonium salt functionalised polyelectrolytes (A-QAS-PEs) were applied. For this purpose, poly(acrylic acid) (PAA) was decorated with different hydrophobic side chains (n-hexane and n-dodecane side entities) and different degrees of substitution (m) of quaternary ammonium groups (abbreviated as PAA-C(O)O-(CH2)n-N+(CH3)3(m); n = 6, 12; m = 8-14%). The grafting approach of PAA with the alkylene quaternary ammonium salt moiety was performed under mild reaction conditions using Steglich esterification followed by quaternisation. The structure of antimicrobial decorated PAA was confirmed by 1H NMR and FTIR, and the mean diameter of all multifunctional microparticles was characterised by SEM. The viscoelastic properties of the functional layers were studied using quartz crystal microbalance with a dissipation (QCM-D). The release of CUR from the microcarriers was described using a hybrid model, i.e., a combination of first-order kinetics and the Korsmeyer-Peppas model. The antimicrobial activity of functionalised PAA and multilayered CUR-loaded hydrogel microcarriers with quaternary ammonium function was assessed against Staphylococcus aureus and Serratia marcescens by the agar diffusion assay method. Only a limited inhibition zone of PAA was observed, but in the case of both antimicrobial decorated PAA and the corresponding multilayered nanocarriers, the inhibitory activity increase was achieved against both strains of bacteria.

Post-Ischemic Brain Neurodegeneration in the Form of Alzheimer's Disease Proteinopathy: Possible Therapeutic Role of Curcumin.

For thousands of years, mankind has been using plant extracts or plants themselves as medicinal herbs. Currently, there is a great deal of public interest in naturally occurring medicinal substances that are virtually non-toxic, readily available, and have an impact on well-being and health. It has been noted that dietary curcumin is one of the regulators that may positively influence changes in the brain after ischemia. Curcumin is a natural polyphenolic compound with pleiotropic biological properties. The observed death of pyramidal neurons in the CA1 region of the hippocampus and its atrophy are considered to be typical changes for post-ischemic brain neurodegeneration and for Alzheimer's disease. Additionally, it has been shown that one of the potential mechanisms of severe neuronal death is the accumulation of neurotoxic amyloid and dysfunctional tau protein after cerebral ischemia. Post-ischemic studies of human and animal brains have shown the presence of amyloid plaques and neurofibrillary tangles. The significant therapeutic feature of curcumin is that it can affect the aging-related cellular proteins, i.e., amyloid and tau protein, preventing their aggregation and insolubility after ischemia. Curcumin also decreases the neurotoxicity of amyloid and tau protein by affecting their structure. Studies in animal models of cerebral ischemia have shown that curcumin reduces infarct volume, brain edema, blood-brain barrier permeability, apoptosis, neuroinflammation, glutamate neurotoxicity, inhibits autophagy and oxidative stress, and improves neurological and behavioral deficits. The available data suggest that curcumin may be a new therapeutic substance in both regenerative medicine and the treatment of neurodegenerative disorders such as post-ischemic neurodegeneration.

Nanodiamond-based multifunctional platform for oral chemo-photothermal combinational therapy of orthotopic colon cancer.

Combination therapy system has become a promising strategy for achieving favorable antitumor efficacy. Herein, a novel oral drug delivery system with colon localization and tumor targeting functions was designed for orthotopic colon cancer chemotherapy and photothermal combinational therapy. The polydopamine coated nanodiamond (PND) was used as the photothermal carrier, through the coupling of sulfhydryl-polyethylene glycol-folate (SH-PEG-FA) on the surface of PND to achieve systematic colon tumor targeting, curcumin (CUR) was loaded as the model drug, and then coated with chitosan (CS) to achieve the long gastrointestinal tract retention and colon localization functions to obtain PND-PEG-FA/CUR@CS nanoparticles. It has high photothermal conversion efficiency and good photothermal stability and exhibited near-infrared (NIR) laser-responsive drug release behavior. Folate (FA) modification effectively promotes the intracellular uptake of nanoparticles by CT26 cells, and the combination of chemotherapy and photothermal therapy (CT/PTT) can enhance cytotoxicity. Compared with free CUR group, nanoparticles prolonged the gastrointestinal tract retention time, accumulated more in colon tumor tissues, and exhibited good photothermal effect in vivo. More importantly, the CT/PTT group exhibited satisfactory tumor growth inhibition effects with good biocompatibility in vivo. In summary, this oral drug delivery system is an efficient platform for chemotherapy and photothermal combinational therapy of orthotopic colon cancer.

The inhibition of interaction with serum albumin enhances the physiological activity of curcumin by increasing its cellular uptake.

Based on the free drug hypothesis, we hypothesized that food compounds that bind stronger to BSA than CUR inhibit the binding between BSA and CUR, and that this results in an increase of the cellular uptake and physiological activities of CUR. To verify this hypothesis, food compounds that bind stronger to BSA than CUR were identified. When THP-1 monocytes were co-treated with the identified compounds (e.g., piperine) and CUR, cell viability significantly decreased, suggesting that the physiological activity of CUR was enhanced. Also, when THP-1 macrophages were co-treated with CUR and the identified compounds following LPS + IFNγ treatment, the decrement of TNF-α was higher compared to treatment with CUR only. Furthermore, the cellular uptake of CUR was increased during this co-treatment. Such results verify our hypothesis, and provide insights into the development of ways to enhance the physiological activities of various food compounds via focusing on their interaction with albumin.

Curcumin combined with photodynamic therapy, promising therapies for the treatment of cancer.

Curcumin, a phytochemical derived from the rhizome of turmeric (Curcuma longa L.), has a broad group of substances with antibacterial, anti-inflammatory, anti-oxidant, anticancer activities. The anticancer activity of curcumin and its derivatives are mainly related to its regulation of signal transduction pathways. However, due to the low oral availability of curcumin, fast metabolism and other pharmacokinetic properties limit the application of curcumin in the treatment of cancer. Evidence suggests that curcumin combined with photodynamic therapy can overcome the limitation of curcumin's low bioavailability by acting on apoptosis pathways, such as B-cell lymphoma 2 (Bcl-2) and caspase family, and affecting cell cycle. This paper reviews the structure and pharmacokinetics of curcumin, focusing on the anticancer activity of curcumin combined with photodynamic therapy and the effects on cancer-related signal pathways.

In vitro release mechanism and cytotoxic behavior of curcumin loaded casein nanoparticles

Abstract In the recent past, drug delivery through nanoparticles is considered an effective tool to treat various diseases. Biopolymeric nanoparticles such as protein based nanoparticles have vital role as drug carrier as it is non-antigenic, and easily biodegradable. Curcumin, plant polyphenolic anticancerous compound was loaded into the casein nanoparticles by coacervation method. Particle size and surface charge of spherical casein nanoparticles as observed to be 201.4 nm and -86.9 mV. The loading efficiency of curcumin loaded casein nanoparticles was found to 85.05 %. In vitro drug release was performed at different pH (7.4 and 3.0), and the cumulative release was observed to be 24.8 and 20.13% and at different temperatures (25°C and 37°C), the cumulative release was observed to be 24.8 and 28.60 % respectively in 48 h. Curcumin release from casein nanoparticles was shown to be in a steady, and prolonged rate. The nanoparticles were observed to have an effective antimocrobial activity than curcumin in free form. The drug loaded casein nanoparticles were found to be potent particles to protect cells from hydrogen peroxide and UV light damage. The cytotoxic activity of nanoparticles on MCF7 and A549 cells were assayed and was observed to have an IC50 value of 609 and 825.2µg/ml. Cell death was observed to be through apoptosis, accompanied by DNA fragmentation.

Curcumin for parkinson´s disease: potential therapeutic effects, molecular mechanisms, and nanoformulations to enhance its efficacy.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Monocarbonyl Analogs of Curcumin Based on the Pseudopelletierine Scaffold: Synthesis and Anti-Inflammatory Activity.

Curcumin (CUR) is a natural compound that exhibits anti-inflammatory, anti-bacterial, and other biological properties. However, its application as an effective drug is problematic due to its poor oral bioavailability, solubility in water, and poor absorption from the gastrointestinal tract. The aim of this work is to synthesize monocarbonyl analogs of CUR based on the 9-methyl-9-azabicyclo[3.2.1]nonan-3-one (pseudopelletierine, granatanone) scaffold to improve its bioavailability. Granatane is a homologue of tropane, whose structure is present in numerous naturally occurring alkaloids, e.g., l-cocaine and l-scopolamine. In this study, ten new pseudopelletierine-derived monocarbonyl analogs of CUR were successfully synthesized and characterized by spectral methods and X-ray crystallography. Additionally, in vitro test of the cytotoxicity and anti-inflammatory properties of the synthesized compounds were performed.

Effect of oxidized dextran on the stability of gallic acid-modified chitosan-sodium caseinate nanoparticles.

We incorporated oxidized dextran (Odex) into nanoparticles composed of gallic acid-modified chitosan (GA-CS) and sodium caseinate (NaCas). The mass ratio of GA-CS to NaCas and the pH of the reaction solution were optimized to obtain nanoparticles with excellent performance and stability. The interactions among various nanomaterials were confirmed by Fourier-transform infrared spectroscopy (FT-IR) and fluorescence spectrometer. The optimized complex nanoparticles had a diameter of approximately 131.2 nm with a polydispersity index (PDI) of 0.14, and a zeta potential of 26.2 mV. Our results showed that Odex enhanced the stability and function of GA-CS/NaCas nanoparticles (NP). At a curcumin loading of 10%, the encapsulation efficiency of Odex-crosslinked GA-CS/NaCas (NP (Odex)) was 96.2%, whereas that for uncrosslinked nanoparticles was 66.9%. Compared to the burst release profile of free curcumin in simulated GI fluids, the sustained release profile of encapsulated curcumin was observed. Radical-scavenging assays confirmed that the nanoparticles had excellent antioxidant activity themselves due to the grafting of phenolic acid on chitosan backbone. Overall, NP (Odex) with good GI stability and antioxidant activity hold promising for the oral delivery of hydrophobic bioactives.

Cellular uptake and apoptotic properties of gemini curcumin in gastric cancer cells.

INTRODUCTION: Curcumin is a polyphenolic natural compound, which has demonstrated to possess antioxidant, anti-inflammatory, and anticancer effects in vitro & in vivo. However, its applicability in cancer therapy has been limited due to its poor cellular uptake. Here, we aimed to evaluate the anticancer effect of novel gemini curcumin (Gemini-Cur) on the gastric cancer AGS cells. METHOD: The AGS cancerous and HFF-2 non-cancerous cells were treated with Gemini-Cur and curcumin (Cur) in a time- and dose-dependent manner. Cellular toxicity was studied using MTT, fluorescence microscopy, annexin V/FITC, and cell cycle assays. Additionally, real-time PCR and western blotting were employed to evaluate the expression of Bax, Bcl-2 and survivin genes. RESULTS: Our data indicated that Gemini-Cur is significantly taken into AGS cells compared to Cur. Moreover, the viability of Gemini-Cur treated cells was significantly reduced in a time- and dose-dependent manner (p < 0.001). Gemini-Cur compound induced G2/M cell cycle arrest that was followed by apoptosis in a time-dependent manner (p < 0.0001). DISCUSSION: Taken together, our findings support the idea that Gemini-Cur has the potential to be considered as an anticancer agent.

A Systematic Approach for Liposome and Lipodisk Preclinical Formulation Development by Microfluidic Technology.

Lipid nanoparticles have transformed the drug delivery field enhancing the therapeutic drug performance of small molecules and biologics with several approved drug products. However, in industry, these more complex drug delivery systems such as liposomes require more material and time to develop. Here, we report a liposome and lipodisk decision tree with model compounds of diverse physicochemical properties to understand how to resourcefully optimize encapsulation efficiency (EE) for these lipid-based drug delivery systems. We have identified trends with physicochemical properties such as Log P, where higher Log P compounds such as curcumin were able to efficiently load into the lipid bilayer resulting in high EE with altering the drug/lipid (D/L) ratio. Moderate Log P compounds such as cyclosporine A and dexamethasone had significantly higher encapsulation in lipodisks, which contain higher amounts of PEG lipid compared to liposomes. The EE of negative Log P compounds, like acyclovir, remained low regardless of altering the D/L ratio and PEG concentrations. In this study, microfluidic techniques were employed to fabricate liposomes and lipodisks formulations allowing for a reproducible strategy for formulation development. Both liposome and lipodisk of curcumin demonstrated enhanced in vivo performance compared with a conventional formulation in the rat pharmacokinetic study. This combination of approaches with multiple model compounds and lipid-based drug delivery systems provides a systematic guidance to effective strategies to generate higher EE with minimal drug waste and expedite the process for preclinical development when applied to industry compounds.

Neuroprotective effects of curcumin-loaded nanophytosome on ketamine-induced schizophrenia-like behaviors and oxidative damage in male mice.

Curcumin as an antioxidant natural herb has shown numerous pharmacological effects. However, the poor bioavailability of curcumin is a significant pharmacological barrier for its antioxidant activities. The present study was conducted to develop curcumin-loaded nanophytosome (CNP) and explore their therapeutic potential in a ketamine (KET)-induced schizophrenia (SCZ) model. The mice in our experiment were treated orally with curcumin and CNP (20 mg/kg) for 30 consecutive days. In addition, the animals received intraperitoneal injection of KET (30 mg/kg/day) from the 16th to the 30th day. SCZ-like behaviors were evaluated employing forced swimming test (FST), open field test (OFT), and novel object recognition test (NORT), and oxidative stress markers in the brain were estimated. Our results revealed that CNP has a greater neuroprotective effect compared to free curcumin. CNP pretreatment significantly ameliorated KET-induced brain injury evidenced by a marked reduction in the depressive and anxiety-like behaviors, memory deficits, and oxidative stress markers in cortical and subcortical tissues. Therefore, CNP, as a suitable drug delivery system, may improve curcumin bioavailability and confer stronger neuroprotective effects against KET-induced behavioral deficits and oxidative damages.