Bulletin of Faculty of Pharmacy, Cairo University最新文献

Preclinical models of immunomodulatory studies are indispensable part in the process of drug discovery and development. Still, they are mimeo of human immunostimulation/suppression provided heterogeneity of latter. This review discusses various preclinical models of immunomodulatory studies viz. cell lines for immunomodulatory studies, murine models include humoral antibody (HA) response, delayed type hypersensitivity response, macrophage phagocytosis by carbon clearance method, effect on total leucocytes count, leucocyte mobilization studies, mice lethality test Fish models include phagocytosis by fish blood lymphocytes, specific and non-specific response in fish and intestinal bacterial colonization; whereas pathogen infestation model includes immunomodulation against Eimeria vermiformis.

A portfolio of these biological models has to be utilized strategically as the specific stage of process of drug discovery. During selection of such model it has to be kept in mind that the model must be physiologically relevant. At the same time, it should be able to aid in prediction of human response. Never the less, apart from being ‘physiologically relevant’, the decisive ‘proof’ regarding safety and efficacy of test drugs lies human studies. Still, sensible construal and envision of data resulting from these models to humans, and a conformingly more prominence placed on medical research during early stage of clinical trials, are therefore indispensable to mend on the clinical study rates for discovery of novel immunomodulatory agents.

Umbelliferone is a 7-hydroxycoumarin that is a pharmacologically active agent. It is widely distributed within the Rutaceae and Apiaceae (Umbelliferae) families and is efficiently extracted using methanol. Umbelliferone is a fluorescing compound used as a sunscreen agent. It is synthesized using the Pechmann condensation reaction of resorcinol and formyl acetic acid. Biosynthetically it is synthesized using the phenylpropanoid pathway. Umbelliferone is a synthon for other coumarins and heterocycles with improved biological activities. In the Literature modest antibacterial and antifungal activities are reported with MIC values of 500–1000 μg/mL, but exhibited good E. coli anti-biofilm formation. Umbelliferone shows good inhibitions of DPPH, hydroxyl, superoxide anion and ABTS radicals. Other reported activities are anti-inflammatory, anti-hyperglycaemic, molluscicidal and anti-tumor activities.

In the present investigation, proniosomes of risperidone were formulated, optimized and evaluated for effective transdermal delivery in order to overcome the bioavailability issues of orally administered risperidone. The proniosomes were prepared using various sorbitan esters with cholesterol and soya lecithin and were evaluated for in-vitro parameters, ex-vivo permeation and in-vivo performance. Results indicated that the vesicles were spherical in shape, their size ranged from 284.00 nm to 941.40 nm and they had high zeta potential. The entrapment efficiency for spans was higher compared to tweens. DSC and IR studies confirmed the absence of chemical interactions between the risperidone and proniosome components. In-vitro release study showed that formulations with spans exhibit controlled release profile and followed the Higuchi model. No significant change in vesicle size and entrapment efficiency was observed when the proniosomes were stored at 4 ± 1 °C and 25 ± 2 °C for three months. Proniosomes with span 60 showed no signs of erythema or edema and has highest flux across the rat skin (169.851 ± 2.13 μg cm⁻² h⁻¹). The relative bioavailability was 92% after transdermal administration of proniosomes and the t_max was increased to 8 h. So we conclude that the developed proniosome formulation would be a promising alternative to improve the bioavailability problems of risperidone.

A new series of N-substituted derivatives of 2-[(5-{1-[(4-chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-yl)sulfanyl]acetamide (6a-w) has been designed and synthesized with multifunctional moieties. The synthesized compounds were evaluated for their antibacterial and anti-enzymatic potential supported by % hemolytic activity. The synthesized compound 5-(1-(4-chlorophenylsulfonyl)-3-piperidinyl)-1,3,4-oxadiazole-2-thiol (3) was stirred with synthesized electrophiles as N-aryl/alkyl/aralkyl-2-bromoacetamide (5a-w) in an aprotic solvent under basic conditions to acquire the target molecules, 6a-w. The spectral analytical techniques of IR, EI-MS, ¹H NMR and ¹³C-NMR were utilized for structural elucidation of synthesized molecules. The antibacterial screening against certain bacterial strains of gram-negative and gram-positive bacteria rendered compound 6i as good inhibitor of gram-negative bacterial strains. The enzyme inhibition revealed low potential against lipoxygenase (LOX) enzyme. The hemolytic study provided valuable information about cytotoxic behavior of synthesized molecules.

Alangium salvifolium has been used traditionally for treatment of various ailments. Almost every part of A. salvifolium including roots, leaves, stem and bark are used in the Ayurveda and Siddha systems of medicines for the treatment of various diseases. In modern scientific literatures, the plant has been reported to have potential efficacy against diabetes, peptic ulcer, arthritis, inflammation and anthelminthic activities etc. A. salvifolium is reported to contain various biologically active phytochemicals such as alangine, ankorine, tubulosine, alangicine, salsoline etc. The present review highlights the traditional uses of different parts of A. salvifolium, its phytochemical constituents with therapeutic activity and the evidence based studies on various pharmacological effects of the plant.

Butoconazole is an imidazole antifungal that is more effective than miconazole and clotrimazole for treatment of vaginal candidiasis. A highly sensitive tandem mass spectrometric assay was developed and validated to evaluate systemic absorption of Butoconazole following intravaginal administration. Chromatographic separation was achieved using Waters Xterra C18 column (3 µm, 3.0 × 50.0 mm). Liquid-liquid extraction using tert-butyl methyl ether was used for preparation of plasma samples. The mobile phase was solvent A: 0.1% formic acid in water and solvent B: acetonitrile: methanol (30:70, v/v), using gradient elution mode at 0.5 mL/min. Detection at positive electrospray ionization in the MRM mode was then employed. Analysis was carried out within 5.5 min over a linear concentration range of 0.10–30.00 ng/mL. Validation was carried out according to US FDA guidelines for bioanalytical method validation. Matrix effect, recovery efficiency and process efficiency have been investigated for the analyte and internal standard in neat solvent, post-extraction matrix and plasma. The mean percentage recoveries were higher than 80%, the accuracy was 93.51–106.85% and the RSD was below 10% throughout the studied concentration range. Results indicated sufficient stability of the target analyte in plasma at the employed experimental conditions. Results of incurred sample re-analysis and incurred sample stability revealed less than 5% variability. The applicability of the assay for monitoring of the systemic absorption of Butoconazole following intra vaginal application to healthy volunteers was demonstrated. Results confirmed that Butoconazole was detected shortly after intra vaginal administration with C_max and t_max of 30 ng/mL and 6 h, respectively.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that affects movement, balance and fine motor control mostly in the elderly population. It is characterized by the progressive loss of neurons in substantia nigra resulting in the depletion of dopamine. Due to ethical reasons the study cannot be performed directly on humans, hence various genetic models of PD based on alpha synuclein, primarily the transgenic over expression of mutant or wild forms in mice or flies are available. In the present the study, we decided to study the effect of myricetin on the climbing ability and life span of PD flies expressing human alpha synuclein in the brain. The PD flies were exposed to 10, 20 and 40 µM of myricetin for 24 days and then assayed for climbing ability. For survival assay the PD flies were transferred to a new diet at 3 day interval having the desired concentration of the myricetin until the last one will die. The PD flies exposed to various doses of myricetin showed not only a dose dependent significant delay in the loss of climbing ability but also increased life span of flies. The results suggest that myricetin is potent in delaying the loss of climbing ability and increases the life span of PD flies expressing human alpha synuclein in the brain.

Schizophrenia is a chronic mental-disorder and one of the top 10 causes of disability globally. Nearly 4.3 million people suffer from schizophrenia in India but very few visit a hospital for diagnosis or treatment. Of those patients who receive treatment, medication non-adherence and decreased quality of life (QOL) are the major problems. The objective of study was to assess the impact of pharmacist-led collaborative patient education on medication adherence and QOL in schizophrenia patients in a psychiatry out-patient setting of a tertiary-care setting. Patients were randomized into two groups. Interventional patients received medication review, followed by patient education session using Patient-Information Leaflets (PILs) developed for the study. Control patients received usual-care. Patients data were collected at the beginning of the study and after each follow-up of one-month interval, till 3rd follow-up. Medication adherence and QOL were assessed using Medication Adherence Rating Scale and WHOQOL-BREF questionnaire respectively. Twenty-three patients completed the study, 13 were in the intervention and 10 in the control group. Majority of the study subjects were of age group 18–39 years (69.56%) and female (65.21%). Medication adherence mean improvement was 0.7 ± 0.67 and 1.75 ± 0.2 in control and intervention groups respectively. Similarly, mean QOL improvement was 16.12 ± 1.98 and 24.17 ± 0.3 in control and intervention groups respectively. Statistically significant improvement in the mean medication adherence and QOL was observed in the intervention group. Results showed that pharmacist-psychiatrist collaborative care can significantly improve patients’ medication adherence and QOL.

Hyperglycemia and oxidative stress are involved in the development of diabetic neuropathy (DN). This study was designed to evaluate the effect of homeopathic preparation of Cephalendra indica (family Cucurbitaceae) mother tincture (MT), 6 C and 30 C potencies on DN in wistar rats. DN was induced by intraperitoneal injection of streptozotocin (60 mg/kg) 15 min after nicotinamide (230 mg/kg, i.p.) administration. Rats were divided into six groups (n = 6). Group 1 and 2 were kept normal control and diabetic control respectively whereas groups 3–5 consist of DN rats treated with different doses of C. indica MT, 6 C and 30 C potencies for 30 days. Gabapentin (30 mg/kg) was used as standard. DN was assessed by thermal (hot plate and tail immersion method) and mechanical hyperalgesia (randell-sellito analgesiometer test), allodynia (von frey hair test), motor nerve conduction velocity (MNCV) and oxidative-nitrosative stress in streptozotocin induced experimental diabetes Tissue antioxidant enzymes (SOD, GSH, TBARS) level was measured to assess the oxidative stress. Also the level of advanced glycation end products (AGEs) in sciatic nerve along with nitrite estimation was determined. MT, 6 C and 30 C potencies of C. indica produced significant attenuation in the biochemical parameters used to assess DN. Moreover, oxidative stress and AGE’s level in sciatic nerve was also found to be significantly reduced. So, it can be concluded that homeopathic potencies of C. indica have protective effect against DN via inhibition of oxidative stress and AGE’s.

In the presented study, orthogonal projection to latent structures (OPLS) is introduced as a data preprocessing method that handles nonlinear data prior to modelling with two well established nonlinear multivariate models; namely support vector regression (SVR) and artificial neural networks (ANN). The proposed preprocessing proved to significantly improve prediction abilities through removal of uncorrelated data.

The study was established based on a case study nonlinear spectrofluorimetric data of agomelatine (AGM) and its hydrolysis degradation products (Deg I and Deg II), where a 3 factor 4 level experimental design was used to provide a training set of 16 mixtures with different proportions of studied components. An independent test set which consisted of 9 mixtures was established to confirm the prediction ability of the introduced models. Excitation wavelength was 227 nm, and working range for emission spectra was 320–440 nm.

The couplings of OPLS-SVR and OPLS-ANN provided better accuracy for prediction of independent nonlinear test set. The root mean square error of prediction RMSEP for the test set mixtures was used as a major comparison parameter, where RMSEP results for OPLS-SVR and OPLS-ANN are 2.19 and 1.50 respectively.