DARU, Journal of Pharmaceutical Sciences
Volume:20 Issue: 1, 2012

Nanotechnology is one of the premiere technologies available today, having expanded both as field of scientific study and in the public consciousness. Despite this growth, the drawbacks, limitations and potential safety hazards associated with the incorporation of nanotechnology into existing industries are still being learned. The noticeable point is that there is no enough data available yet to analyze global use of nanotechnology from a meta-perspective. Three challenges can be defined in light of nanotoxicology. One, materials that might prove to be significantly toxic must be identified. Two, a system for the categorization of NP materials must be codified and made available to toxicologists. Third, a better understanding of nanoparticles biological interactions must be obtained, in order to make the best use of the first two goals. For all three, it must be remembered that research standards need to be developed for the gathering of data on the nanoscale, as that level is where the NPs and the patient''s biosystems will be interacting.As requiring toxicologists to become nanotechnology experts would not be feasible, to properly incorporate the care of nanotoxicity into the existing medical framework, a range of experts across multiple fields of study must work in close synchronization. The focus needs to be on mechanism-driven research to ensure a solid scientific foundation for the assessment of NP and their role in healthcare.

Background and the purpose of the study:Carvedilol nonselective beta-adrenoreceptor blocker, chemically (+/-)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxypHenoxy) ethyl] amino]-2-propanol, slightly soluble in ethyl ether; and practically insoluble in water, gastric fluid (simulated, TS, pH 1.1), and intestinal fluid (simulated, TS without pancreatin, pH 7.5) Compounds with aqueous solubility less than 1% W/V often represents dissolution rate limited absorption. There is need to enhance the dissolution rate of carvedilol. The objective of our present investigation was to compare chitosan and chitosan cholorhydrate based various approaches for enhancement of dissolution rate of carvedilol. The different formulations were prepared by different methods like solvent change approach to prepare hydrosols, solvent evaporation technique to form solid dispersions and cogrind mixtures. The prepared formulations were characterized in terms of saturation solubility, drug content, infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), electron microscopy, in vitro dissolution studies and stability studies. The practical yield in case of hydrosols was ranged from 59.76 to 92.32%. The drug content was found to uniform among the different batches of hydrosols, cogrind mixture and solid dispersions ranged from 98.24 to 99.89%. There was significant improvement in dissolution rate of carvedilol with chitosan chlorhdyrate as compare to chitosan and explanation to this behavior was found in the differences in the wetting, solubilities and swelling capacity of the chitosan and chitosan salts, chitosan chlorhydrate rapidly wet and dissolve upon its incorporation into the dissolution medium, whereas the chitosan base, less water soluble, would take more time to dissolve. This technique is scalable and valuable in manufacturing process in future for enhancement of dissolution of poorly water soluble drugs.

Background and the purpose of the study: The purpose of this study was to prepare pegylated poly lactide-co-glycolide (PEG-PLGA) nanoparticles (NPs) loaded with roxithromycin (RXN) with appropriate physicochemical properties and antibacterial activity. Roxithromycin, a semi-synthetic derivative of erythromycin, is more stable than erythromycin under acidic conditions and exhibits improved clinical effects. RXN was loaded in pegylated PLGA NPs in different drug;polymer ratios by solvent evaporation technique and characterized for their size and size distribution, surface charge, surface morphology, drug loading, in vitro drug release profile, and in vitro antibacterial effects on S. aureus, B. subtilis, and S. epidermidis. Results and NPs were spherical with a relatively mono-dispersed size distribution. The particle size of nanoparticles ranged from 150 to 200 nm. NPs with entrapment efficiency of up to 80.0+/-6.5% and drug loading of up to 13.0+/-1.0% were prepared. In vitro release study showed an early burst release of about 50.03+/-0.99% at 6.5 h and then a slow and steady release of RXN was observed after the burst release. In vitro antibacterial effects determined that the minimal inhibitory concentration (MIC) of RXN loaded PEG-PLGA NPs were 9 times lower on S. aureus, 4.5 times lower on B. subtilis, and 4.5 times lower on S. epidermidis compared to RXN solution. In conclusion it was shown that polymeric NPs enhanced the antibacterial efficacy of RXN substantially.

Aegle marmelos leaf, seed and fruit from earlier studies is known to affect male fertility in reversible manner. However they had delayed onset and recovery was found to be prolonged. The present study was undertaken with an aim to evaluate the effect of Aegle marmelos bark extract on rats as the extract is found to be a rich source of marmin and fagarine known for reducing male fertility. Three different concentration of methanolic bark extracts of Aegle marmelos (L.) were evaluated for male antifertility activity on albino wistar rats. Methanolic bark extract of Aegle marmelos at the dose of 200, 400, and 600 mg/Kg b.w was administered orally for 60 days. Treatments were stopped thereafter and animals were sacrificed after a recovery period of 30 days. Control animal were administered vehicle (0.5% CMC for 60 days). Lonidamine was used as standard drug to compare the effect of extract. Methanolic extract causes a dose & duration dependent infertility via reducing reproductive organ weight and serum testosterone levels. Sperm analysis results showed reduction in sperm density, motility, viability and sperm acrosomal integrity without interfering libido and vital organ body weight. Histopathological studies of testes revealed exfoliation of elongated spermatids, nuclear chromatin condensation, degeneration and prominent spaces detected within the germinal epithelium signifying testicular cytotoxicity and necrosis. Time dependent complete infertility was observed in all dose levels. Animals after the withdrawal from treatment, for 30 days showed restoration of the morphological as well as physiological parameters in extract treated rats. Methanolic extract showed lipid lowering activity compared to control, suggestive good candidature of this plant for further studies. Our studies suggested Aegle marmelos barks methanolic extract as strong candidate for male contraceptive via its ability to produce complete inhibition of pregnancy, rapid restoration of fertility after withdrawal from treatment and its lipid correcting ability proving further beneficial effects.

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb) has intensified efforts to discover novel drugs for tuberculosis (TB) treatment. Targeting the persistent state of Mtb, a condition in which Mtb is resistant to conventional drug therapies, is of particular interest. This study is focused on propargyl acetate derivatives. 8 molecules were designed based on propargyl alcohols and different acid anhydrides. All the synthesized compounds and commercial available compounds were evaluated for anti-tuberculosis activity. Inhibitors against Mtb have been identified and characterized for further development into potential novel anti-tubercular drugs.

Background and purpose of the study: The aim of this study was to investigate the effect of cinnamaldehyde on mucositis and salivary total antioxidant capacity in gamma-irradiated rats. The study was conducted on 28 male Wistar rats, 7--11 weeks of age and 160 +/- 20 g body weight, divided into four groups of seven rats each. The first group receiving normal saline (S), the second group receiving saline and gamma radiation (SR), the third group receiving 50 mg/kg cinnamaldehyde 98% (C), and the fourth group receiving 50 mg/kg cinnamaldehyde 98% and gamma radiation (CR). SR and CR groups were exposed to 15 Gy gamma irradiation for 7 min and 39 s. Rats were intraperitoneally injected each day during the 10-day period of the experiment, and their tongues and lips were examined to assess the incidence and severity of mucositis. The saliva samples were taken from the animals three times on day zero, six, and ten. The mean mucositis incidence appeared to be delayed in the CR than the SR group (P = 0.024), and the severity was significantly higher in the SR compared to the CR group;the difference was statistically significant on the second day (P = 0.027). In the evaluation of salivary antioxidant capacity, salivary antioxidant concentration was significantly higher in the C than the S, SR, and CR groups on the tenth day of the experiment (p <0.05). The clinical effects in the CR group seem to be due to antioxidant, anti-bacterial and anti-inflammatory effects of cinnamaldehyde; this conclusion, however, requires further investigations. Delayed antioxidant effect in the CR group was evident in ip cinnamaldehyde injection, the exact mechanism is not clear.

Physician prescribing is the most frequent medical intervention with a highest impact on healthcare costs and outcomes. Therefore improving and promoting rational drug use is a great interest. We aimed to assess the effectiveness and cost-effectiveness of two forms of conducting prescribing audit and feedback interventions and a printed educational material intervention in improving physician prescribing. Method/design: A four-arm randomized trial with economic evaluation will be conducted in Tehran. Three interventions (routine feedback, revised feedback, and printed educational material) and a no intervention control arm will be compared. Physicians working in outpatient practices are randomly allocated to one of the four arms using stratified randomized sampling. The interventions are developed based on a review of literature, physician interviews, current experiences in Iran and with theoretical insights from the Theory of Planned Behavior. Effects of the interventions on improving antibiotics and corticosteroids prescribing will be assessed in regression analyses. Cost data will be assessed from a health care provider''s perspective and incremental cost-effectiveness ratios will be calculated. This study will determine the effectiveness and cost-effectiveness of three interventions and allow us to determine the most effective interventions in improving prescribing pattern. If the interventions are cost-effective, they will likely be applied nationwide.

Background and the purpose of the study: The objectives of the present study were phytochemical screening and study of the effects of ethanolic extract of aerial parts of Ocimum basilicum (basil) on cardiac functions and histopathological changes in isoproterenol-induced myocardial infarction (MI). The leaves of the plant were extracted with ethanol by maceration and subjected to colorimetry to determine flavonoids and phenolic compounds. High-performance TLC analysis and subsequent CAMAG''s TLC scanning were performed to quantify rosmarinic acid content. Wistar rats were assigned to 6 groups of normal control, sham, isoproterenol, and treatment with 10, 20, and 40 mg/kg of the extract two times per day concurrent with MI induction. A subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used to induce MI. Phytochemical screening indicated the presence of phenolic compounds (5.36%) and flavonoids (1.86%). Rosmarinic acid was the principal phenolic compound with a 15.74% existence. The ST-segment elevation induced by isoproterenol was significantly suppressed by all doses of the extract. A severe myocardial necrosis and fibrosis with a sharp reduction in left ventricular contractility and a marked increase in left ventricular end-diastolic pressure were seen in the isoproterenol group, all of which were significantly improved by the extract treatment. In addition to in-vitro antioxidant activity, the extract significantly suppressed the elevation of malondialdehyde levels both in the serum and the myocardium. The results of the study demonstrate that Ocimum basilicum strongly protected the myocardium against isoproterenol-induced infarction and suggest that the cardioprotective effects could be related to antioxidative activities.

Cancer is one of the most prominent human diseases which has enthused scientific and commercial interest in the discovery of newer anticancer agents from natural sources. Here we demonstrated the anticancer activity of ethanolic extract of aerial parts of Pupalia lappacea (L) Juss (Amaranthaceae) (EAPL) on Chronic Myeloid Leukemia K562 cells. Antiproliferative activity of EAPL was determined by MTT assay using carvacrol as a positive control. Induction of apoptosis was studied by annexin V, mitochondrial membrane potential, caspase activation and cell cycle analysis using flow cytometer and modulation in protein levels of p53, PCNA, Bax and Bcl2 ratio, cytochrome c and cleavage of PARP were studied by Western blot analysis. The standardization of the extract was performed through reverse phase-HPLC using Rutin as biomarker. The results showed dose dependent decrease in growth of K562 cells with an IC50 of 40 +/- 0.01 mug/ml by EAPL. Induction of apoptosis by EAPL was dose dependent with the activation of p53, inhibition of PCNA, decrease in Bcl2/Bax ratio, decrease in the mitochondrial membrane potential resulting in release of cytochrome c, activation of multicaspase and cleavage of PARP. Further HPLC standardization of EAPL showed presence 0.024 % of Rutin. Present study significantly demonstrates anticancer activity of EAPL on Chronic Myeloid Leukemia (K562) cells which can lead to potential therapeutic agent in treating cancer. Rutin, a known anti cancer compound is being reported and quantified for the first time from EAPL.

This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA). Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering and transmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger. The polymeric micelles prepared in this study could entrap up to 43.2+/-2.27 mug of ITRA per milliliter. All micelles showed mean diameter between 120--200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58x10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF) varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process. In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.

Background and purpose of the study: Diabetes mellitus has been recognized as a major risk factor for osteoporosis in which bone turnover is affected by different mechanisms. As the morbidity, mortality and financial cost related to osteoporosis are expected to rise in Iran in coming years, and considering the efficacy of Angipars(R) for improvement of different ulcers which made it a new herbal drug in diabetic foot ulcer, there is a need to evaluate the effect of this new drug on different organs including bone resorption and bone formation markers. In this randomized, double- blind clinical trial, 61 diabetic patients were included. The subjects were randomly divided into intervention and control groups. Subjects of intervention group received 100 mg of Angipars(R) twice a day. Laboratory tests including bone resorption and bone formation markers were performed at baseline and after 3 months. 31 patients in study group and 30 patients in control group finished the study. The mean age of the study population and the mean disease duration was respectively 51.8 +/- 6.2 and 7.5 +/- 4.7 years with no significant differences between intervention and control patients. No statistically significant differences between patients and controls were observed in pyridinoline, osteocalcin, urine calcium, bone alkaline phosphatase and tumor necrosis factor (TNF-alpha). Only urine creatinine level significantly changed between two groups after 3 month of treatment (p-value: 0.029) In conclusion, the findings of this study indicate that Semelil (Angipars(R)) had no beneficial or harmful effects on bone. It might be other effects of this new component on bone turnover process which need more studies and more time to be discovered.

The prevalence of Pediatric Functional Constipation (FC) has been reported between 0. 7% to 29. 6%. This study was conducted to compare the laxative effect of cassia fistula emulsion (CFE) with mineral oil (MO) on FC. Cassia fistula is named in Traditional Iranian Medicine (TIM) as «Folus». Materials and methods A randomized clinical trial was carried on 81 children (age range: 4-13 years) with FC, according to Rome III criteria in Amirkola Children''s Hospital, Babol, Iran. They received CFE or MO randomly for three weeks. CFE was produced according to the order of TIM references. Children were counted as improved when they exited from Rome III criteria of FC. Frequency of defecation, fecal incontinence, retentive posturing, severity of pain, consistency of stool and anal leakage of oily material were compared between the two groups and with baselines. An intent-to-treat analysis was used. Safety of drugs was assessed with the evaluation of clinical adverse effects. 41 children were assigned randomly to receive CFE and 40 children received MO. After three weeks of medication, 84% of children in CFE group and 50% in MO group (p = 0. 002) exited from the criteria of FC, so called improved. All measurable criteria improved in both groups. The frequency of defecation in CFE group improved from 1. 7 per week (before the study) to 10. 6 per week (at the third week) while this parameter differed in MO group from 2 to 6. 1 (p < 0. 001). The severity of pain during defecation and consistency of stool improved significantly better in CFE group than MO group (p < 0. 05), but there were not any significant differences between the two groups in fecal incontinence and retentive posturing. Anal leakage of oily material occurred as an important complication in MO group while the children in CFE group did not complaint it. Drug''s compliances were not significantly different in the two groups. CFE and MO did not cause clinically significant side effects. CFE was most effective than MO in the 3-week treatment of children with FC.