Curcumin and nano-curcumin applications in psychiatric disorders.

Psychiatric disorders cause long-lasting disabilities across different age groups. While various medications are available for mental disorders, some patients do not fully benefit from them or experience treatment resistance. The pathogenesis of psychiatric disorders involves multiple mechanisms, including an increase in the inflammatory response. Targeting inflammatory mechanisms has shown promise as a therapeutic approach for these disorders. Curcumin, known for its anti-inflammatory properties and potential neuroprotective effects, has been the subject of studies investigating its potential as a treatment option for psychiatric disorders. This review comprehensively examines the potential therapeutic role of curcumin and its nanoformulations in psychiatric conditions, including major depressive disorder (MDD), bipolar disorder, schizophrenia, and anxiety disorders. There is lack of robust clinical trials across all the studied psychiatric disorders, particularly bipolar disorder and schizophrenia. More studies have focused on MDD. Studies on depression indicate that curcumin may be effective as an antidepressant agent, either alone or as an adjunct therapy. However, inconsistencies exist among study findings, highlighting the need for further research with improved blinding, optimized dosages, and treatment durations. Limited evidence supports the use of curcumin for bipolar disorder, making its therapeutic application challenging. Well-designed clinical trials are warranted to explore its potential therapeutic benefits. Exploring various formulations and delivery strategies, such as utilizing liposomes and nanoparticles, presents intriguing avenues for future research. More extensive clinical trials are needed to assess the efficacy of curcumin as a standalone or adjunctive treatment for psychiatric disorders, focusing on optimal dosages, formulations, and treatment durations.

Antibacterial and Cellular Behaviors of Novel Zinc-Doped Hydroxyapatite/Graphene Nanocomposite for Bone Tissue Engineering.

Bacteria are one of the significant causes of infection in the body after scaffold implantation. Effective use of nanotechnology to overcome this problem is an exciting and practical solution. Nanoparticles can cause bacterial degradation by the electrostatic interaction with receptors and cell walls. Simultaneously, the incorporation of antibacterial materials such as zinc and graphene in nanoparticles can further enhance bacterial degradation. In the present study, zinc-doped hydroxyapatite/graphene was synthesized and characterized as a nanocomposite material possessing both antibacterial and bioactive properties for bone tissue engineering. After synthesizing the zinc-doped hydroxyapatite nanoparticles using a mechanochemical process, they were composited with reduced graphene oxide. The nanoparticles and nanocomposite samples were extensively investigated by transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Their antibacterial behaviors against Escherichia coli and Staphylococcus aureus were studied. The antibacterial properties of hydroxyapatite nanoparticles were found to be improved more than 2.7 and 3.4 times after zinc doping and further compositing with graphene, respectively. In vitro cell assessment was investigated by a cell viability test and alkaline phosphatase activity using mesenchymal stem cells, and the results showed that hydroxyapatite nanoparticles in the culture medium, in addition to non-toxicity, led to enhanced proliferation of bone marrow stem cells. Furthermore, zinc doping in combination with graphene significantly increased alkaline phosphatase activity and proliferation of mesenchymal stem cells. The antibacterial activity along with cell biocompatibility/bioactivity of zinc-doped hydroxyapatite/graphene nanocomposite are the highly desirable and suitable biological properties for bone tissue engineering successfully achieved in this work.

Drug release kinetic analysis and prediction of release data via polymer molecular weight in sustained release diltiazem matrices.

This study was conducted to investigate the effects of HPMC (K4M and K100M) as well as tragacanth on the drug release rate of diltiazem (DLTZ) from matrix tablets prepared by direct compression method.Mechanism of drug transport through the matrices was studied by fitting the release data to the 10 kinetic models. 3 model independent parameters; i. e., mean dissolution time (MDT), mean release rate (MRR) and release rate efficacy (RE) as well as 5 time point approaches were established to compare the dissolution profiles. To find correlation between fraction of drug released and polymer's molecular weight, dissolution data were fitted into two proposed equations.All polymers could sustain drug release up to 10 h. The release data were fitted best to Peppas and Higuchi square root kinetic models considering squared correlation coefficient and mean percent error (MPE). RE and MRR were decreased when polymer to drug ratio was increased. Conversely, t60% was increased with raising polymer /drug ratio. The fractions of drug released from the formulations prepared with tragacanth were more than those formulated using the same amount of HPMC K4M and HPMC K100M.Preparation of DLTZ matrices applying HPMCK4M, HPMC K100M and tragacanth could effectively extend the drug release.

Micro-suspension coating method: a new approach in formulation and development of controlled porosity osmotic pump systems.

PURPOSE: The aim of this study was to design and evaluate diltiazem hydrochloride controlled porosity osmotic pump (CPOP) system employing a new coating technique named the micro suspension coating method. METHOD: In this method the fast dissolving pore formers were suspended in polymeric coating solution as micronized particles. Cellulose acetate and dextrose were used as film former polymer and pore former, respectively. 4 comparative parameters i. e., D24h (cumulative release percent after 24 h), Devzero (mean percent deviation of drug release from zero order kinetic), tL (lag time of the drug release) and RSQzero were used to assess various formulations. RESULTS: The results showed a significant increase of D24h due to the decrease in the thickness of the semipermeable membrane (SPM) and increase of the sucrose concentration (P<0.05). An inverse relationship was seen between sucrose amounts and drug release lag times of the formulations. In addition, lag time was significantly reduced following addition of tween 80 to SPM formulation (P<0.05). Results of scanning electron microscopy studies exhibited formation of pores in the membrane from where the drug release occurred. CONCLUSION: Micro suspension coating method was found to be a novel and promising method to formulate CPOP system of diltiazem hydrochloride.

The effect of Beta-cyclodextrin on percutaneous absorption of commonly used Eusolex® sunscreens.

BACKGROUND: There is a serious concern about the topical and systemic absorption of organic ultraviolet filters in sunscreen formulations and subsequent phototoxic and photo allergic reactions. Ideally, a sunscreen should localize in the surface of stratum corneum and create a barrier against UV radiation, but not penetrate into the underlying viable tissues and systemic circulation. PURPOSE: The objective of the present study was to determine the effects of ß-cyclodextrin (ß-CDX) complexation on the transdermal penetration of 3 commonly used sun blocking agents, Eusolex ® 4360 (avobenzone), Eusolex ® 9020 (Oxybenzone) and Eusolex ® 232 (Ensulizole). METHODS: The complexation of the sunscreen agents with ß-CDX was performed by 3 methods and confirmed by differential scanning calorimetry (DSC). Sunscreens, and their physical mixtures and complexes with ß-CDX were introduced into a model cream base (o/w emulsion). To find out the influence of ß-CDX, sunscreen creams were applied to the rat skin in vitro in standard Franz diffusion cells and the amount of sunscreen permeated after 6 h was assessed by HPLC. RESULTS: The skin penetration flux of the UV filters was significantly reduced (4­15 fold) by complexation with ß-CDX. Complexation also could prolong absorption lag time of sun blocking agents to more than 150 min. CONCLUSION: Considering the ability of ß-CDX complexation in the reduction of flux and enhancement ratio as well as prolongation of absorption lag time, this technique could be very helpful for reducing systemic absorption of the UV filters and subsequent toxicity and allergic reaction.

The effect of pore-formers and plasticizers on the release kinetic of diltiazem hydrochloride from the controlled porosity osmotic pumps.

BACKGROUND: The aim of this study was to design a controlled porosity osmotic pump (CPOP) tablet of diltiazem hydrochloride (DLTZ) to deliver the drug according to the zero order kinetic model over 24 h. METHOD: CPOPS were prepared by incorporating DLTZ in the tablet core followed by coating with cellulose acetate solution containing various types of pore-formers (PVP, PEG 2000, PEG 6000 and PEG 20000) and plasticizers (glycerol, castor oil and diethylphthalate). In vitro release study was conducted for the prepared formulations and the dissolution profiles were compared throughout four parameters, namely, D24 h (cumulative release in 24 h), tL (lag time), RSQzero (squared correlation coefficient of zero order kinetic) and MPDzero (mean percent deviation from zero order equation). RESULTS: Scanning electron microscopy showed formation of the pores in the semi-permeable membrane after coming in contact with dissolution medium. All formulations released more than 76% of contained drug during 24 h. CONCLUSION: Drug release rate and lag time were found to be directly proportional to the type and concentration of pore-formers as well as hydrophilicity of plasticizers. Our findings indicated that by optimizing formulation variables, CPOP tablets obeying zero order drug release kinetic could be obtained.

Preparation and evaluation of sustained release calcium alginate beads and matrix tablets of acetazolamide.

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Serum concentrations and hypoglycemic effect of gliclazide: crosspovidone solid dispersion on streptozotocin induced diabetic rats.

Gliclazide is practically insoluble in water and its GI absorption is limited by its dissolution rate. Our previously published works indicated that preparing gliclazide-crosspovidone solid dispersion in the drug/ carrier ratio of 1:1 using cogrinding technique is able to enhance drug dissolution rate. The coground of gliclazide-crosspovidone was administrated to the rats and the hypoglycemic effects of pure drug, a physical mixture and the coground were considered in 3 groups of rats weighing 200-250 g (n=6). The rats were made diabetic by single intravenous administration of streptozotocin (60 mg/kg). Each of the rats received a single dose of gliclazide (equivalent to 40 mg/kg) as pure drug, physical mixture and coground in an aqueous suspension. Glucose level was assessed via glucometer after collecting the blood samples from tail vein. Gliclazide concentration in plasma was assessed applying high pressure liquid chromatography. According to 1-way ANOVA, Student-Newman-Keuls test, the coground revealed enhanced hypoglycemic effects as well as higher serum gliclazide concentration relative to pure drug and its corresponding physical mixture in the all sampling times. The area under serum glucose concentration curve vs. time for the pure gliclazide, physical mixture and coground formulations were 3 090.5±79, 3 018.8±96 and 2 374.0±73 mg.h/dl, respectively. Correspondingly, their area under serum gliclazide concentration curve vs. time were 1 171.8±156.8, 1 379.5±96.2 and 4 827.7±637.5 µg.h/ml. It follows that; formulation of gliclazide-crosspovidone coground is able to improve oral absorption of the drug.