Technological Innovation in Pharmaceutical Research Vol. 2

With the current emergence of Novel Drug Delivery Systems, mucoadhesive drug delivery systems march outs its significance as a unique novel drug delivery system in the present scenario. The mucosal or mucoadhesive drug delivery system plays a key role as a innovative drug delivery system in the field of Novel Drug Delivery Systems. The term mucoadhesion in a simplier manner signifies the adhesion of two materials with each other where one of the material is the mucosal surface. Certain investigations are on progress to find out an alternative route which can bypass hepatic metabolism, reduce dose frequencies and prolong the drug action. In those cases, delivery of drugs through buccal cavity can be brought up into the real picture. The dosage forms of mucoadhesive drug delivery system includes solids, semisolids and transparent drug loaded films. This when comes into contact with the buccal mucous membrane, drug tends to release at a sustained and controlled manner through the blood capillaries associated in the buccal cavity assuring maximum bioavailibility and thereby increases the ease of drug administration, bypasses hepatic portal systems and gastrointestinal tract, increase in therapeutic efficacy, improved patient compliance and reduction in dose frequencies. With the influx of a large number of new drug molecules due to drug discovery, mucoadhesive drug delivery will play an even more important role in delivering these molecules.

Treatment of severe malaria continues to rely on two plant derived drugs: artesunate and quinine. In this short overview, the use of effective antimalarial drug combinations against extremely mutable parasite Plasmodium falciparum is reviewed.

Extracts from the mistletoe plant Viscum album L. (VE) are used in the complementary cancer therapy in Europe for decades. VE contain several compounds like the mistletoe lectins (ML) 1-3 and viscotoxins (VT), but also several minor ingredients. ML-1 is suggested to be the main anti-tumor component of VE, VT induce cell death, and some minor compounds can strengthen the anti-tumor activity of ML-1. ML stimulate the immune system, induce cytotoxicity, are able to modify the expression of cancer-associated genes and influence the proliferation and motility of tumor cells.

In this study we determine the anti-tumor effects of the VE ISCADOR Qu, of recombinant ML-1 (Aviscumine) and of native ML-1 in the treatment of glioblastoma (GBM), the most common brain tumor in adults. Additionally, we were determined whether a mistletoe-based therapy, if used as adjuvant treatment in combination with temozolomide(TMZ)-or irradiation, provide synergistic effects. The expression of the ML receptor CD75s, which is expressed in GBM specimen and cells, but not in the normal brain, correlates well with the drug-induced cytotoxicity. In GBM cells, the drugs induce cell death in a concentration-dependent manner, induce an arrest in the G₂/M phase and provide synergistic and additive anti-tumor effects. A single intratumoral application of Aviscumine prolonged the survival of GBM mice longer than tumor irradiation and was even better if used in combination with radio-chemotherapy. This indicates that an adjuvant treatment of glioma patients with ML-containing drugs might be beneficial.

Diseases caused by microorganisms have been managed traditionally using medicinal plants, as they contain components of therapeutic value. In this context, in the present study, phytochemical analysis of ethanol, methanol, acetone and aqueous extracts of Ocimum tenuiflorum and its antibacterial activities were investigated. Leaves of Ocimum tenuiflorum were shade dried, powdered, and extracted using solvents such as ethanol, methanol, acetone and water. Preliminary phytochemical screening of the crude leaf extracts revealed the presence of various bioactive compounds such as alkaloids, terpenoids, flavonoids, tannins, steroids, anthraquinones, saponins, resins, glycosides and phenols. The antibacterial activity of Ocimum tenuiflorum leaf extracts was evaluated against Staphylococcus aureus, Salmonella gallinarum, Pseudomonas fluorescens, Escherichia coli and Proteus vulgaris using agar disc diffusion technique. Ethanolic leaf extract of Ocimum tenuiflorum exhibited maximum zone of inhibition (18.33 ± 0.47 mm) against salmonella gallinarum. The maximum activity index (2.48 ± 0.30) and increase in fold area (5.22 ± 1.47) were observed against Escherichia coli for aqueous leaf extract. The results obtained from the current study confirm that Ocimum tenuiflorum can be used as a source of drugs to fight infections caused by susceptible bacteria.

¹²³I-Metaiodobenzylguanidine (MIBG) scintigraphy is a widely used functional imaging tool with a high degree of sensitivity and specificity in diagnosis of pheochromocytoma. However, rare cases of false positive reactions have been reported. A 67-year-old male patient was admitted with epigastric pain. Abdominal computed tomography (CT) revealed a heterogeneous left adrenal mass 6 cm in diameter; following hormone testing, ¹²³I-MIBG scintigraphy was performed to determine the presence of pheochromocytoma, which confirmed eccentric uptake by a large left adrenal gland mass. Chest CT and PET-CT confirmed metastatic lymphadenopathy; therefore, endobronchial ultrasound transbronchial needle aspiration was performed. Metastatic carcinoma of unknown origin was suspected from a lymph node biopsy and surgical resection was performed for definitive diagnosis and correction of excess hormonal secretion. A final diagnosis of undifferentiated adrenal malignant tumor was rendered, instead of histologically malignant pheochromocytoma, despite the uptake of MIBG demonstrated by scintigraphy. When the degree of MIBG uptake is low-grade in relationship to a large tumor mass, then a false-positive result should be entertained, particularly in the absence of typical clinical and biochemical features of pheochromocytoma.

Introduction: Foreign body-associated sialadenitis of submandibular gland is not often and scarce within the literature. In this study, a report of a piece of Nail-like fish bone foreign body entering the Wharton’s duct causing an acute sialadenitis is presented.

Foreign bodies must be explored and all suspected areas must be examined carefully for avoiding secondary problems and surgeries in the future. The mechanism of foreign-body entry is generally traumatic, thus reports of a foreign body entering the salivary gland intraorally through Wharton’s or Stensen’s duct are not common and usual.

Foreign bodies in the oral and maxillofacial region are often experienced after trauma and dental treatment.

Case Report: We describe a case of obstructive sialadenitis in the submandibular gland caused by penetration of a fish bone in a 68-year-old man. He had swelling and spontaneous pain in the left submandibular region. The radiographic examination didn't show foreign body in the submandibular gland. Initially, we diagnosed obstructive sialadenitis in the left submandibular gland and the study suspect that salivary stone might be the cause of this swelling so compressing and milking of Wharton duct. The foreign body measured 1.3 cm *3 mm*2 mm and was a nail-like object. On pathological examination, the foreign body was found to be a fish bone (cartilage-like organic material).

Conclusion: This case demonstrated that precise and proper inspection and examination, milking and then paying attention to the secretion of salivary gland lead to proper diagnosis and after that suitable treatment, so this could reduce costly assessment and treatment, also lessen bewilderment of the patient. At the end, milking and pay attention to transparency (glassiness) and canescent of secretion of salivary gland are helpful for achievement of proper diagnosis.

Background: Arsenic is an environmental chemical of toxicological concern today since it has been shown to be a human genotoxin and carcinogen.

Aims: The aim of this study was to determine the genotoxic effect in HepG2 cells of the four arsenic compounds by measuring DNA damage, depletion of cellular glutathione (GSH) as a measure of oxidative stress as well as antioxidant agent and apoptotic and necrotic events.

Study Design: Arsenic is an environmental chemical of toxicological concern today since it has been shown to be a human genotoxin and carcinogen. This project investigated four forms of inorganic arsenic: arsenate (As⁺⁵), sodium arsenite (As⁺³), arsenic trioxide (As₂O₃) and dimethyl arsenic acid (DMA⁺⁵); a major metabolite of arsenate.

Methodology: HepG2 cells (1.5x10⁵/ml) treated with the four arsenics (10 µM) for 24 hr. Harvested cells were analysed for GSH concentration by reverse phase HPLC with fluorescence detection. Cells were investigated for DNA damage using the Comet assay. Cells were analysed by flow cytometry to detect apoptosis and necrosis, all running in parallel.

Results: The DNA damage for cells dosed with DMA or As₂O₃ was not significantly different from control. However, significant DNA damage was seen for cells treated with arsenite and arsenate (p<0.001, p<0.05 respectively). Reduced glutathione was increased by arsenic compounds compared to control. However, this was only statistically significant for arsenite (p<0.001) and arsenate (p<0.05). Whereas, results not indicated apoptosis and necrosis in viable adherent cells although this was not statistically different.

Conclusions: All four arsenicals appeared to increase GSH content and DNA damage compared to control especially both arsenite and arsenate significantly are different. Further experiments are required to assess the mechanism(s) of genotoxicity of the arsenicals in GSH depletion.

The present study deals with photo protection benefit of Evefresh cream. Personal care industries are aggressively competing and crowding the market with wide variety of sun screeners and SPF products to offer sun protection benefit to the customers. We have used a rapid and an extremely sensitive tool- cyanotype paper to study the effect of the cream. The findings show that Evefresh cream provides photo protection and hence may be of great medical use for SLE patients to achieve photo protection from short exposure to sun. Evefresh cream being a face cream is regular use will certainly enable the users to achieve the above benefits. The paper reports the findings in detail. The findings clearly highlight in non-exaggerated manner the medical importance of Evefresh cream for SLE and actinic keratosis patients.

This work aimed to investigate the phytochemical, antioxidant and antibacterial activities of the various colors wild grape fruits extracted by different solvents; water, methanol and ethanol. The total phenolic (TPC) and flavonoid (TFC) contents were analyzed by Folin-Ciocalteu and colorimetric aluminum chloride assays, respectively, while antioxidant activities were determined using 2,2?-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. The antibacterial activity against infective bacteria using agar well diffusion method of the extracts was also tested. Methanolic extracts showed the highest of TPC comparison to other extracts, especially in green extract. The ethanolic extracts of red and black fruits showed the highest of TFC whereas the green extract using methanol showed the highest TFC. The methanolic extracts of all color showed the lowest of IC₅₀ values when compared to other solvents in the same color. Among them, the methanolic extract of green has the lowest of IC₅₀ values which considered to be the highest powerful of antioxidant activity. The obtained results were directly trend with the FRAP values. However, the ethanolic extract showed similar antioxidant activity as comparison to the methanolic extract. The methanolic extract from green fruits showed good antibacterial activity. All ethanolic extracts showed widely and similarly on selected bacteria inhibition, but no activity was observed in all water extracts. The MIC and MBC of all extracts were in ranged of 250-500 µg/mL. The obtained results revealed that extraction solvents and different colors of wide grape fruits were the main factors on the phytochemicals and biological activities of the wild grape.

Diazoxide (DZ) is a well known cardioprotective drug capable of mimicking ischemic preconditioning. Being primarilly a pharmacological opener of mitochondrial ATP-sensitive potassium channels (mK_ATP channels), DZ is known to produce multiple side effects because of its interactions with different cellular targets (such as plasma membrane K_ATP channels, F₀F₁ ATP synthase, succinate dehydrogenase and others), capable of confounding an understanding of direct bioenergetic effects of mK_ATP channels opening in mitochondria. In this review direct and off-target effects of DZ were discussed. The emphasis was made on molecular basis of DZ interaction with K_ATP channels and different K_ATP channels isoforms sensitivity to this drug. The present knowledge on DZ interaction with mK_ATP channels is outlined as well as DZ interactions with other molecular targets affecting mitochondrial functions and bioenergetics. Conclusion was reached that high sensitivity of mK_ATP channel to DZ shown in our studies allows for avoiding off-target effects of this drug in studies on isolated mitochondria, which makes it a useful tool for an appraisal of diverse functional effects of mK_ATP channel opening.

Objectives: CTHepaB is a traditional Vietnamese medicinal formulation used to prevent liver disorders. This study sought to evaluate the effects of CTHepaB for the treatment of cirrhosis, induced by carbon tetrachloride (CCl₄) combined with alcohol, high-fat, and iron diet in Wistar rats, in vivo.

Materials and Methods: Cirrhosis in Wistar rats was induced by the subcutaneous injection of CC1₄ (5.0 ml/kg), once per week for 10 weeks. Rats were then fed with a diet containing 20% fat, 0.05% cholesterol, and iron oxalate. Rats were provided with plain water each day and were provided with water mixed with 30% ethanol on 1 day. The rats were randomly divided into 5 groups and given distilled water, CC1₄, silymarin (70 mg/kg/24 h), or CTHepaB (at 0.56 and 1.12 g/kg/24 h) for 4 weeks, after which blood samples were collected for biochemical tests and the livers were dissected to evaluate weight and morphology and 4-hydroxyproline was quantified to evaluate fibrosis and collagen accumulation.

Results: In cirrhotic Wistar rats, CTHepaB, at both 0.56 and 1.12 g/kg/24 h, reduced the activity of the enzymes aspartate transaminase (AST) and alanine transaminase (ALT) in the blood (p < 0.01), increased plasma albumin levels and decreased prothrombin times (p < 0.05). CTHepaB treatment also improved the rats’ physical conditions, decreased hydroxyproline concentrations in the liver, and reduced the level of cirrhosis, as assessed on Masson’s trichrome-stained templates. The effects of CTHepaB were dose-dependent manner, equivalent to silymarin at the dose of 70 mg/kg/24 h.

Conclusion: CTHepaB was effective for the treatment of a cirrhosis model in Wistar rats.

Aims: The study aimed to phytochemically investigate the n-butanol soluble fraction of Indigofera hirsuta aerial parts and to evaluate the anti-inflammatory activity of the fraction using laboratory animal models.

Study Design: Isolation and elucidation of the bioactive compounds and anti-inflammatory activity investigation on n-butanol soluble fraction.

Place and Duration of Study: Department of Pharmaceutical and Medicinal Chemistry, Ahmadu Bello University, Zaria - Nigeria. The study was completed between January-October, 2011.

Methodology: The compounds isolated were identified using different spectroscopic techniques. The n-butanol fraction was investigated for its effect on carrageenan-induced oedema in rat’s experimental model.

Results: Two Flavonol glycosides were isolated; Kaempferol-3-O-?-D-glucopyranoside (T2) and Kaempferol-7-O-?-D-glucopyranoside (Q3).The fraction significantly (P = .05) inhibited the carrageenan-induced paw oedema at doses of 150 and 300 mg/kg tested. The percentage anti-inflammatory effect of the highest dose tested (300 mg/kg) at the peak hour was higher than that of ketoprofen (10 mg/kg), the standard anti-inflammatory agent.

Conclusion: The result of this research suggests that the n-butanol soluble fraction of Indigofera hirsuta aerial parts contains bioactive compounds with anti-inflammatory activity.

Three new unsymmetrical porphyrins bearing meso-functionlization have been synthesized and characterized. The structural assignment of these porphyrins was based on UV-visible, IR, ¹H NMR, mass, spectra and elemental analysis. The Present communication deals with new methodology for the synthesis of porphyrins, which is different from the general synthetic procedure developed by Adler. Meso-substituted porphyrins bearing specific patterns of functional groups are valuable components in the synthesis of porphyrin-based biomemetic systems and molecular materials.