Correction to: Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.

[This corrects the article DOI: 10.1007/s40200-022-01074-4.].

Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.

Objectives: Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer's disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)-induced rats. Methods: Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (Na+K+-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab. Results: Metformin treatment significantly (p < 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO (p < 0.01 and p < 0.05). The lipid profile was significantly (p < 0.001) controlled with cardiometabolic functions. Conclusions: Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline.

SGLT inhibitors as antidiabetic agents: a comprehensive review.

Diabetes is one of the most common disorders that substantially contributes to an increase in global health burden. As a metabolic disorder, diabetes is associated with various medical conditions and diseases such as obesity, hypertension, cardiovascular diseases, and atherosclerosis. In this review, we cover the scientific studies on sodium/glucose cotransporter (SGLT) inhibitors published during the last decade. Our focus on providing an exhaustive overview of SGLT inhibitors enabled us to present their chemical classification for the first time.

Effect of Resveratrol on biofilm formation and virulence factor gene expression of Porphyromonas gingivalis in periodontal disease.

Periodontal disease is an oral inflammatory disease that destroys the tooth supporting periodontal tissues resulting in tooth loss. Porphyromonas gingivalis is a keystone pathogen that plays a significant role in periodontitis. In previous studies, resveratrol has shown significant results by targeting inflammatory and adhesive markers. Virulence factors of P. gingivalis play an important role in the bacterial adhesion and colonization. In this study, we aimed to demonstrate the anti-biofilm and anti-bacterial activity of resveratrol and also study the effect of resveratrol on the expression of virulence factor genes of P. gingivalis using reverse transcriptase polymerase chain reaction (RT-PCR). The anti-microbial and anti-biofilm activity of resveratrol on P. gingivalis was carried out by broth microdilution assay and biofilm adhesion reduction-crystal violet assay, respectively. We carried out the gene expression analysis by RT-PCR with the P. gingivalis treated compound to analyze the change in the expression of virulence factors: fimbriae and gingipain. Minimal inhibitory concentrations (MIC) of resveratrol against P. gingivalis and other clinical strains are in the range of 78.12-156.25 µg/mL. Resveratrol dose-dependently prevented the biofilm formation and also attenuated the virulence of P. gingivalis by reducing the expression of virulence factor genes such as fimbriae (type II and IV) and proteinases (kgp and rgpA). Resveratrol demonstrated superior anti-bacterial and anti-biofilm activity against P. gingivalis. There was significant reduction in the expression of fimbriae and gingipain with the resveratrol-treated compound. The results suggest that resveratrol, due to its multiple actions, may become a simple and inexpensive therapeutic strategy for treating periodontal disease.

Stability studies of pure and mixture form of curcuminoids by reverse phase-HPLC method under various experimental stress conditions.

Since time immemorial, turmeric has been widely marketed and consumed as dietary supplement due to its diverse medicinal properties. Curcuminoids-comprising a mixture of curcumin (CUR), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)-are the prime bioactive constituents of turmeric. However, the usage of curcuminoids is limited by their chemical instability. The lack of information on comparative stability profiles of curcuminoids (in pure and mixture form) prompted us to study how pure curcuminoids and their mixtures behave under different stress degradation conditions. The order of stability of curcuminoids when exposed to acidic, alkaline, and oxidative degradation was found to be as follows: BDMC > DMC > CUR. While the pure and mixture forms of curcuminoids were stable against heat, they completely degraded upon exposure to sunlight. The degradation extent of curcuminoids (in mixture form) was substantially less as compared to their pure form; therefore, this suggested the synergistic stabilizing influence of DMC and BDMC in the curcuminoids' mixture.

Hesperidin, a citrus flavonoid, protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress, endothelial dysfunction and neurotoxicity in Wistar rats.

CONTEXT: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties. OBJECTIVE: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats. MATERIALS AND METHODS: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100 mg/kg), HSP-per se (100 mg/kg) and donepezil (0.1 mg/kg). HHcy was induced by oral administration of l-methionine (1.7 g/kg) for 32 days. From the 14th day of study HSP (25, 50 and 100 mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28th-32nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done. RESULTS: HSP (100 mg/kg) treatment in l-methionine-treated rats exhibited significant (p < 0.001) dose-dependent activity and reduced behavioural deficits, brain acetylcholinesterase (25.99 ± 2.36 versus 10.73 ± 1.26 µmoles/mg), brain lipid peroxidation (15.25 ± 1.65 versus 6.18 ± 0.74 nM/mg), serum homocysteine (Hcy) (22.37 ± 0.30 versus 11.01 ± 1.01 µg/mL) and serum cholesterol (182.7 ± 2.15 versus 101.5 ± 2.76 mg/dL) and increased brain antioxidant levels. HSP significantly (p < 0.001) reduced endothelial dysfunction (ED) by abolishing the effect of l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations. CONCLUSION: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.

Effects of fisetin on hyperhomocysteinemia-induced experimental endothelial dysfunction and vascular dementia.

This study was designed to investigate the effects of fisetin (FST) on hyperhomocysteinemia (HHcy)-induced experimental endothelial dysfunction (ED) and vascular dementia (VaD) in rats. Wistar rats were randomly divided into 8 groups: control, vehicle control, l-methionine, FST (5, 10, and 25 mg/kg, p.o.), FST-per se (25 mg/kg, p.o.), and donepezil (0.1 mg/kg, p.o.). l-Methionine administration (1.7 g/kg, p.o.) for 32 days induced HHcy. ED and VaD induced by HHcy were determined by vascular reactivity measurements, behavioral analysis using Morris water maze and Y-maze, along with a biochemical and histological evaluation of thoracic aorta and brain tissues. Administration of l-methionine developed behavioral deficits; triggered brain lipid peroxidation (LPO); compromised brain acetylcholinesterase activity (AChE); and reduced the levels of brain superoxide dismutase (SOD), brain catalase (CAT), brain reduced glutathione (GSH), and serum nitrite; and increased serum homocysteine and cholesterol levels. These effects were accompanied by decreased vascular NO bioavailability, marked intimal thickening of the aorta, and multiple necrotic foci in brain cortex. HHcy-induced alterations in the activities of SOD, CAT, GSH, AChE, LPO, behavioral deficits, ED, and histological aberrations were significantly attenuated by treatment with fisetin in a dose-dependent manner. Collectively, our results indicate that fisetin exerts endothelial and neuroprotective effects against HHcy-induced ED and VaD.

Vanillic Acid Ameliorates Cationic Bovine Serum Albumin Induced Immune Complex Glomerulonephritis in BALB/c Mice.

Preclinical Research Vanillic acid (VA) is a dihydroxybenzoic acid derivative widely used as a flavoring agent. It has chemopreventive effects on experimentally-induced carcinogenesis and in ulcerative colitis. The object of the present study was to investigate the effects of VA, alone and in combination with methylprednisolone (MP), on cationic bovine serum albumin (cBSA induced immune-complex glomerulonephritis in female BALB/c mice. Pre-immunization was carried out with cBSA in BALB/c mice and repeated (cBSA, 13 mg/kg, 3 times/week, i.v.) for 6 weeks to induce glomerulonephritis which was confirmed by the presence of severe proteinuria. The effect of VA (50, 100, and 200 mg/kg, p.o.) and its combination with MP (12.5 mg/kg, p.o.) was assessed in the nephrotic disease model. Treatment with VA decreased inflammatory nephrotic injury as evidenced by decreased proteinuria, serum creatinine, blood urea nitrogen, serum IgG1 and TNF-α levels. Co-administration of VA with MP showed an improvement in the immunohistochemistry of glomerular nephrin and podocin. The present results indicate that VA has a nephroprotective effect in the management of autoimmune nephritis. Drug Dev Res 77 : 171-179, 2016. © 2016 Wiley Periodicals, Inc.

Antiproliferative, ACE-inhibitory and functional properties of protein hydrolysates from rohu (Labeo rohita) roe (egg) prepared by gastrointestinal proteases.

Previously, we have reported the chemical composition, molecular mass distribution and antioxidant activity of rohu roe protein hydrolysates. In the current study, antiproliferative, angiotensin-converting enzyme (ACE)-inhibitory activities and functional properties of protein hydrolysates from rohu (Labeo rohita) roe proteins, prepared by gastrointestinal proteases (pepsin and trypsin), were investigated. Antiproliferative activity was evaluated against human colon cancer cell line Caco-2. The results showed that the pepsin hydrolysate possessed dose dependent inhibitory effect on Caco-2 cell line. Pepsin and trypsin hydrolysates displayed ACE-inhibitory activity in vitro. The ACE-inhibitory activity of the hydrolysate generated by pepsin (47 ± 1.7 %, at 1 mg/ml) is higher than that obtained by trypsin (36 ± 3.2 %). Additionally, the undigested rohu roe proteins and its hydrolysates exhibited functional properties. Solubilities of the hydrolysates were above 81 ± 9.2 % at all pH values tested. Pepsin and trypsin hydrolysates showed good foaming capacity (45-211 %) and emulsification activity (4-29 m(2)/g). The foaming abilities and emulsifying activity index (EAI) were affected by pH. The results suggest that protein hydrolysates from rohu roe could be useful in food industry for various applications.

Antioxidant activity and functional properties of enzymatic protein hydrolysates from common carp (Cyprinus carpio) roe (egg).

Previously, we have reported the composition, molecular mass distribution and in vivo immunomodulatory effects of common carp roe protein hydrolysates. In the current study, antioxidative activity and functional properties of common carp (Cyprinus carpio) roe (egg) protein hydrolysates, prepared by pepsin, trypsin and Alcalase, were evaluated. The three hydrolysates showed excellent antioxidant activities in a dose dependent manner in various in vitro models such as 2,2 diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, 2,2'-azino-bis(3-ethylbenzthiazoline-6)-sulfonic acid (ABTS(+)) radical scavenging activity, ferric reducing antioxidant power (FRAP) and ferrous ion (Fe(2+)) chelating ability. Enzymatic hydrolysis significantly increased protein solubility of the hydrolysates to above 62 % over a wide pH range (2-12). Carp roe hydrolysates exhibited good foaming and emulsification properties. The results suggest that bioactive carp roe protein hydrolysates (CRPHs) with good functional properties could be useful in health food/nutraceutical/pharmaceutical industry for various applications.

Chemical composition and immunomodulatory effects of enzymatic protein hydrolysates from common carp (Cyprinus carpio) egg.

OBJECTIVES: The aim of this study was to prepare protein hydrolysates from underutilized common carp (Cyprinus carpio) egg and to investigate their immunomodulatory effects in vivo. METHODS: Common carp (Cyprinus carpio) egg (roe) was hydrolysed by pepsin, trypsin, and Alcalase. Chemical composition (proximate, amino acid, mineral and fatty acid compositions) and molecular mass distribution of the three hydrolysates were determined. The carp egg protein hydrolysates (CEPHs) were evaluated for their immunomodulatory effects in BALB/c mice. CEPHs (0.25, 0.5 and 1 g/kg body weight) were orally administered daily to female BALB/c mice (4-6 wk, 18-20 g) for a period of 45 d. After 45 d, mice were sacrificed and different tissues were collected for the immunologic investigations. RESULTS: The three hydrolysates contained high protein content (64%-73%) with all essential amino acids, and good proportion of ω-3 fatty acids, especially docosahexaenoic acid. Molecular mass analysis of hydrolysates confirmed the conversion of large-molecular-weight roe proteins into peptides of different sizes (5-90 kDa). The three hydrolysates significantly enhanced the proliferation of spleen lymphocytes. Pepsin hydrolysate (0.5 g/kg body weight) significantly increased the splenic natural killer cell cytotoxicity, mucosal immunity (secretory immunoglobulin A) in the gut and level of serum immunoglobulin A. Whereas Alcalase hydrolysate induced significant increases in the percentages of CD4+ and CD8+ cells in spleen. CONCLUSIONS: The results demonstrate that CEPHs are able to improve the immune system and further reveal that different CEPHs may exert differential influences on the immune function. These results indicate that CEPHs could be useful for several applications in the health food, pharmaceutical, and nutraceutical industries.

Improved anti-diabetic activity of glibenclamide using oral self nano emulsifying powder.

The objective of the present study was to improve solubility, dissolution rate and therapeutic efficacy of a BCS Class II drug, glibenclamide by using oral self nano emulsifying powder. The powder was prepared by adsorbing the mixture of oil, surfactant and co-surfactant onto a carrier with large surface area; Aerosil 200. The ratios of oil and Smix (surfactant/co-surfactant mixture) required to produce an emulsion was optimized based on percentage transmittance studies and particle size determinations. The optimized formulation was subjected to in vitro dissolution study and in vivo therapeutic efficacy in rabbits by monitoring blood glucose levels. Scanning electron microscopy, differential scanning calorimetry and X-ray powder diffraction studies revealed that the drug was present in amorphous form in the final formulation. The in vivo study in rabbits indicated the improved therapeutic efficacy of glibenclamide in self-nanoemulsifying powder compared to plain drug.

Solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of glimepiride: development and antidiabetic activity in albino rabbits.

CONTEXT: This study presents novel self-nanoemulsifying drug delivery system potential of oral delivering which leads poorly aqueous soluble drug glimepiride. OBJECTIVE: The objective of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) for the improved oral delivery of glimepiride and to evaluate its therapeutic efficacy in albino rabbits. RESULTS AND DISCUSSION: The droplet size analyses revealed a droplet size of less than 200 nm. The solid state characterization of S-SNEDDS by scanning electron microscopy (SEM), X-ray powder diffraction and differential scanning calorimetry (DSC) revealed the absence of crystalline glimepiride in the S-SNEDDS. The in vitro dissolution studies revealed that the significant improvement in glimepiride release characteristics. The effect of S-SNEDDS on therapeutic efficacy of glimepride was assessed in albino rabbits by monitoring blood glucose levels and compared with free drug suspension, L-SNEDDS. The S-SNEDDS showed significant (p < 0.05) increase in in vitro drug release and therapeutic efficacy as compared with free drug. CONCLUSION: This study demonstrated that S-SNEDDS is a promising novel drug delivery system of glimepride to enhance oral delivery.

Enhancement of solubility, dissolution release profile and reduction in ulcerogenicity of piroxicam by inclusion complex with skimmed milk.

CONTEXT: Piroxicam (PXM), a non-steroidal anti-inflammatory drug which is poorly soluble in water and ulcerogenic. Milk has been used against the gastric disturbances caused by non-steroidal anti-inflammatory drugs. In this study, skimmed milk (SKM) is used as the carrier for inclusion complex (IC) due to its surface active agent and amino acid content. PURPOSE: To enhance the solubility, dissolution rate and prevent ulcerogenicity of PXM though IC with SKM. METHODS: IC of PXM were prepared with SKM by solvent evaporation method using rota evaporator and were evaluated for solubility, dissolution, solid state characterization, drug excipient interaction, rat intestinal permeation, ulcerogenicity and histopathological studies. RESULTS: Solubility of PXM was enhanced 2.5 times with IC. The dissolution release and amount of PXM permeated through rat small intestine was enhanced significantly with IC. Decreases in the gastric lesion index values of IC were observed than physical mixture (PM) and free PXM. The histopathological studies revealed significant reduction in ulceration in rat stomach after treatment with IC. CONCLUSION: It is concluded that SKM is a good carrier to prepare IC of PXM for oral administration.

Drug-drug interaction between voriconazole and oral hypoglycemic agents in diabetic rats.

OBJECTIVE: The objective was to study the of drug-drug interaction between voriconazole and oral hypoglycemic agents in normal and alloxan induced diabetic rats. MATERIALS AND METHODS: The study was designed in two phases. In the first phase, influence of glibenclamide (0.45 mg/kg, p.o.) and pioglitazone (2.7 mg/kg, p.o. once daily) on blood glucose levels in normoglycemic rats was studied and then influence of voriconazole (18 mg/kg, p.o. twice daily.) pre-treatment on the hypoglycemic activity studied. Simultaneously the influence of voriconazole treatment for seven consecutive days (per se effect) on blood glucose levels was also studied in normoglycemic rats. In the second phase of the study alloxan-induced diabetic rats were used to find out the influence of voriconazole pre-treatment on glibenclamide and pioglitazone induced hypoglycemic effect in pathophysiological condition. Blood samples were collected from retro orbital plexus at regular intervals of 0.0, 0.5, 1.0, 2.0, 4.0, 8.0, 12.0, 18.0 and 24.0 h after drug treatment. All the blood samples were analyzed for plasma glucose by glucose oxidase peroxidase method (GOD/POD). RESULTS: The therapeutic dose of voriconazole potentiates the hypoglycemic activity of glibenclamide and pioglitazone both in normoglycemic and diabetic rats respectively. CONCLUSION: The results indicate that the dose of oral hypoglycemic agents needs to be adjusted if co-administered with voriconazole.

Erythropoietin protects polychlorinated biphenyl (Aroclor 1254) induced neurotoxicity in mice.

Erythropoietin is a hematopoietic cytokine factor with various biological effects and its receptors are expressed in the central nervous system, which helps in normal brain development and exerts neuroprotection in different models of brain injury. The present study was designed to evaluate the neuroprotective role of erythropoietin in Aroclor 1254 induced oxidative stress in mice. Neurotoxicity was induced by Aroclor 1254 (10 mg/kg bw/day). Erythropoietin was administered simultaneously with Aroclor 1254 for 14 days in co-treatment groups and administered before induction of neurotoxicity for 7 days in case of pretreatment groups. To assess the behavioural parameters in observation with learning and memory, open field and Y-maze were employed. Acetylcholinesterase, glutamate, antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) were estimated in brain tissue and corticosterone in plasma to evaluate the intensity of oxidative signalling in brain. Triglycerides and total cholesterol were estimated in plasma. Both doses of erythropoietin (500 and 1000 IU/kg) pretreatment and co-treatment, (i) significantly increased the habituation memory and percentage alteration which are indicative of the cognitive improvement, (ii) attenuated the Aroclor 1254 induced rise in acetylcholinesterase activity, corticosterone, triglycerides and total cholesterol, (iii) increased the glutamate and antioxidant enzyme levels. These results indicate that erythropoietin protects against Aroclor 1254 induced neurotoxicity and improves the cognitive function and that this cytokine could be a promising therapeutic agent for stress induced neurodegeneration.

ß-Hydroxybutyric acid grafted solid lipid nanoparticles: a novel strategy to improve drug delivery to brain.

Delivery of drugs to brain is an elusive task in the therapy of many serious neurological diseases. With the aim to create a novel formulation to enhance the drug uptake to brain, betreliesoxybutyric acid (HBA) grafted docetaxel loaded solid lipid nanoparticles (HD-SLNs) were explored. Transportation of HD-SLNs relies on the transport of novel ligand, HBA, by monocarboxylic acid transporter (MCT1). Expression of MCT1 transporter on brain endothelial cells (bEnd cells) was studied using immunocytochemistry. Stearylamine-HBA conjugate was used to modify the surface of SLNs and it was confirmed using XPS (X-Ray Photon Spectroscopy) analysis. In vitro release studies revealed the controlled release of drug from HD-SLNs. Cytotoxicity and cell uptake studies revealed the increased uptake of docetaxel with HD-SLNs. Mechanism involved in the uptake of HD-SLNs was studied in bEnd cells by saturating MCT1 with excess HBA. Pharmacokinetic and brain distribution demonstrated increased docetaxel concentrations in brain compared with Taxotere®. FROM THE CLINICAL EDITOR: The authors of this study demonstrate enhanced drug delivery to the brain using a novel formulation of beta-hydroxybutyric acid grafted docetaxel loaded solid lipid nanoparticles. The results show increased uptake of docetaxel compared with Taxotere.

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design.

CONTEXT: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets. OBJECTIVE: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole. METHODS: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed. RESULTS: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage. CONCLUSION: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

Increased brain uptake of docetaxel and ketoconazole loaded folate-grafted solid lipid nanoparticles.

Docetaxel is used in the treatment of many types of cancer, but its entry into the brain is restricted by p-glycoprotein (p-gp) efflux. A potential drug-drug interaction exists between docetaxel and ketoconazole because both agents are metabolized hepatically by the cytochrome P-450 system, and ketoconazole can inhibit p-gp efflux of docetaxel at blood brain barrier. Hence, these two drugs were loaded in solid lipid nanoparticles (SLNPs) and surface of these NPs were modified with folic acid for brain targeting. These NPs were characterized for particle size, zeta potential, entrapment efficiency, in vitro drug release, cytotoxicity, and cell uptake in brain endothelial cell lines. Plasma and brain pharmacokinetics have shown increased brain uptake of docetaxel with surface-modified dual drug-loaded SLNPs. Brain permeation coefficient (K(in)) of folate-grafted docetaxel and ketoconazole loaded SLNPs was 44 times higher than that of Taxotere. Hence, these NPs were suitable for the delivery of lipophilic anticancer drugs to the brain. FROM THE CLINICAL EDITOR: In this paper, successful delivery of docetaxel and ketoconazole is reported using solid lipid nanoparticles surface modified with folic acid for brain targeting, which may pave the way to optimized clinical applications of lipophilic anticancer drugs to the brain.