Pharmaceutical aspects of silver nanoparticles.

Silver nanoparticles are particles in the size ranging between 1 and 100 nm. The two major methods used for synthesis of silver nanoparticle are the physical and chemical methods with the disadvantage that they are expensive and can also have toxicity. Biological method is being used as an expedient alternative, as this approach is environment-friendly and less toxic and it includes plant extracts, microorganism, fungi, etc. The major applications of silver nanoparticles in the medical field include diagnostic applications and therapeutic applications, apart from its antimicrobial activity. Due to their nanotoxicity, AgNPs have a several drawbacks too. This review presents a complete view of the mechanism of action, synthesis, the pharmacokinetics of silver nanoparticles, different formulations of AgNPs used in biomedical applications, infertility management, antibacterial effects, skin damage, burns, cancer treatment, etc. and various applications of silver nanoparticles together with the possible toxicological challenge.

Nanostructured lipid carriers based nanogel for meloxicam delivery: mechanistic, in-vivo and stability evaluation.

AIM: Our investigation was aimed to investigate the potential suitability of meloxicam-loaded nanostructured lipid carriers (MLX-NLC) gel for topical application. MAIN METHODS: MLX-NLC gel was prepared and in vivo skin penetration ability of the NLC gel was evaluated using confocal laser scanning microscopy. We studied the effect of MLX-NLC gel on the changes in lipid profile of skin to get an insight into its skin penetration enhancement mechanism. Acetic acid induced writhing test was performed to evaluate the analgesic effect. Drug concentration-time profile of MLX in rat plasma and skin after topical and oral treatment with MLX-NLC gel and oral MLX-solution, respectively, was observed. MLX-NLC gel was subjected to primary skin irritation test, sub-acute dermal toxicity study. Storage stability of MLX-NLC gel was also assessed for 90 days. KEY FINDINGS: NLC gel was effective in permeating Rhodamine 123 to deeper layers of rat skin. Changes in skin lipid prolife were observed in the rat skin on treatment with MLX-NLC gel and the results supported skin lipid extraction as a possible penetration enhancement mechanism. MLX-NLC gel demonstrated sustained pain inhibitory effect. Pharmacokinetics study established that topical application of MLX-NLC gel had the potential to avoid systemic uptake and hence the risk of systemic adverse effects. MLX-NLC gel demonstrated good skin tolerability and biosafety. Excellent physical stability of nanogel was observed at 4 ± 2 °C. SIGNIFICANCE: The study revealed that NLC gel is a promising carrier system for the topical application of MLX without side effects.

Screening of efficient arbuscular mycorrhizal fungi for Azadirachta indica under nursery condition: a step towards afforestation of semi-arid region of western India.

To optimize nursery practices for efficient plant production procedures and to keep up to the ever growing demand of seedlings, identification of the most suitable species of arbuscular mycorrhizal fungi (AMF), specific for a given tree species, is clearly a necessary task. Sixty days old seedlings of Neem (Azadirachta indica A. Juss) raised in root trainers were inoculated with six species of AMF and a mixed inoculum (consortia) and kept in green house. Performances of the treatments on this tree species were evaluated in terms of growth parameters like plant height shoot collar diameter, biomass and phosphorous uptake capabilities. Significant and varied increase in the growth parameters and phosphorous uptake was observed for most of the AMF species against control. Consortia culture was found to be the best suited AMF treatment for A. indica, while Glomus intraradices and Glomus mosseae were the best performing single species cultures. It is the first time in the state of Gujarat that a wide variety of AMF species, isolated from the typical semi-arid region of western India, were tested for the best growth performance with one of the most important tree species for the concerned region.

Screening of efficient arbuscular mycorrhizal fungi for Azadirachta indica under nursery condition: a step towards afforestation of semi-arid region of western India

To optimize nursery practices for efficient plant production procedures and to keep up to the ever growing demand of seedlings, identification of the most suitable species of arbuscular mycorrhizal fungi (AMF), specific for a given tree species, is clearly a necessary task. Sixty days old seedlings of Neem (Azadirachta indica A. Juss) raised in root trainers were inoculated with six species of AMF and a mixed inoculum (consortia) and kept in green house. Performances of the treatments on this tree species were evaluated in terms of growth parameters like plant height shoot collar diameter, biomass and phosphorous uptake capabilities. Significant and varied increase in the growth parameters and phosphorous uptake was observed for most of the AMF species against control. Consortia culture was found to be the best suited AMF treatment for A.indica, while Glomus intraradices and Glomus mosseae were the best performing single species cultures. It is the first time in the state of Gujarat that a wide variety of AMF species, isolated from the typical semi-arid region of western India, were tested for the best growth performance with one of the most important tree species for the concerned region.

Biowaiver: an alternative to in vivo pharmacokinetic bioequivalence studies.

Bioequivalence is a vital concern in drug development even more significant in the case of Narrow Therapeutic Index (NTI) drugs. In clinical development of New Chemical Entities (NCE), bioequivalence studies necessitate to be performed when the formulation of the pharmaceutical dosage form has been changed. In vivo pharmacokinetic data can be used as surrogate parameters for in vivo solubility and permeability data. The Biopharmaceutics Classification System (BCS) has emerged as a helpful tool in product development by alluding to the in vivo performance of the active substance. The bio-relevance of the BCS properties and the in vitro release are best expressed through a correlation between in vitro and in vivo data. Recently BCS has been implemented for waiving bioequivalence studies on the basis of the solubility and gastrointestinal permeability of drug substance and can be strategically deployed to save time and resources during generic drug development. The BCS has been adopted as a very useful tool for in vivo drug design and development worldwide, particularly in terms of regulatory standards. A BCS-based biowaiver has become an important and cost-saving tool in approval of generic drugs.

Effect of Solanum nigrum and Ricinus communis extracts on histamine and carrageenan-induced inflammation in the chicken skin.

We studied anti-inflammatory effect of ethanolic extract of Solanum nigrum leaves and Ricinus communis root bark using chicken skin as model. Leaves of these plants were dried under shade and powdered. 5% Ethanol extracts were prepared using Soxhlet and injected intraperitoneally (400 mg/kg) 1 hour prior to the induction of inflammation. Inflammatory lesion were induced by intradermal injection of 0.02 ml 0.05%w/v histamine (0-2 min, 15 min, 30 min, 1 hr and 6 hr) and 1% w/v carrageenan (0-2 min, 30 min, 1 hr, 6 hr, 12 hr and 48 hr) in different group of birds. Increase in vascular permeability was studied using Evans blue as a permeability marker both qualitatively and quantitatively. Cellular events were studied in skin lesions at various time intervals and cells were counted at high power objective under microscope. Both, extracts exhibited significant decrease in permeability response at an early stage (0-2 min) of histamine as well as in carrageenan induced inflammatory lesions. There was a significant (p< 0.05) suppression in the emigration of heterophils, monocytoid cells, basophils and total leukocytosis in Solanum nigrum and Ricinus communis pretreated chicken skin lesions as compared to the control. The present study suggested antihistamine and anti-inflammatory properties of ethanolic extract of Solanum nigrum and Ricinus communis.

Extensively drug resistance (XDR) tb is not always fatal.

The chance of incidence of XDR TB is on the rise due to improper use of second line anti-tubercular drugs. XDR-TB is very difficult to treat successfully and is often referred to as "virtually untreatable form of TB". We herein report a case of XDR TB confirmed by bacteriological examination in a WHO recognised laboratory who after 12 months of regular treatment improved both clinically and radiologically with sputum smear conversion. To the best of our knowledge, there has been no previous report of any similar case in literature.

Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation.

The aim of the present study was to prepare and characterize novel vesicular carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory agent diclofenac for its sustained and targeted delivery. Elastic liposomes of diclofenac were prepared and characterized in vitro and in vivo. The effect of different formulation variables like type of surfactant, concentration of surfactant and dose of drug on transdermal flux, amount of drug deposited into the skin, muscle and plasma concentration was investigated. The biological activity of optimized formulation was evaluated using carrageenan induced rat paw edema model and results were compared with commercial hydrogel formulation. The elastic liposomal formulations achieved muscle drug concentration between 2.2+/-0.14 to 5.3+/-0.22 microg/g at 12 hr. The same dose of commercial hydrogel formulation produced drug levels between 0.41+/-0.07 to 1.1+/-0.09 microg/g in the muscle. Plasma concentration study showed regiospecificity of elastic liposomal formulation. The results of in vivo study revealed that incorporation of diclofenac in elastic liposomes increased its biological activity two fold as compared to commercial hydrogel formulation. The results of the present study demonstrated greater effectiveness of dermaly applied diclofenac elastic liposomal formulation in comparison to conventional delivery system. The optimized elastic liposomal formulation offers a promising means for the non-invasive treatment of local pain and inflammation by topical application.

Transfersomes--a novel vesicular carrier for enhanced transdermal delivery: development, characterization, and performance evaluation.

This work describes the use of a novel vesicular drug carrier system called transfersomes, which is composed of phospholipid, surfactant, and water for enhanced transdermal delivery. The transfersomal system was much more efficient at delivering a low and high molecular weight drug to the skin in terms of quantity and depth. In the present study transfersomes and liposomes were prepared by using dexamethasone as a model drug. The system was evaluated in vitro for vesicle shape and size, entrapment efficiency, degree of deformability, number of vesicles per cubic mm, and drug diffusion across the artificial membrane and rat skin. The effects of surfactant type, composition, charge, and concentration of surfactant were studied. The in vivo performance of selected formulation was evaluated by using a carrageenan-induced rat paw edema model. Fluorescence microscopy by using rhodamine-123 and 6-carboxyfluorescein as fluorescence probe was performed. The stability study was performed at 4 degrees C and 37 degrees C. An in vitro drug release study has shown a nearly zero order release of drug and no lag phase. The absence of lag phase in comparison to liposomes and ointment is attributed to the greater deformability, which may account for better skin permeability of transfersomes. In vivo studies of transfersomes showed better antiedema activity in comparison to liposomes and ointment, indicating better permeation through the penetration barrier of the skin. This was further confirmed through a fluorescence microscopy study. Finally, it may be concluded from the study that complex lipid molecules, transfersomes, can increase the transdermal flux, prolong the release, and improve the site specificity of bioactive molecules.

Analgesic and anti-inflammatory effects of phosphodiesterase inhibitors.

The aim of the present study was to investigate the role of phosphodiesterase (PDE) enzyme inhibitors namely rolipram and theophylline in pain and inflammation in experimental animals. Rolipram, a selective PDE IV inhibitor and theophylline a nonspecific PDE inhibitor exerted dose dependent analgesic and anti-inflammatory effect against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. Nimesulide (1, 2 mg/kg) produced significant anti-inflammatory effect. Further, nimesulide (0.5 mg/kg) potentiated analgesic effect of rolipram but it failed to modulate the anti-inflammatory effect of PDE inhibitors. Present study suggests that PDE enzymes might be playing a role in nociceptive and inflammatory responses in animals.

Antinociceptive and anti-inflammatory effects of Tanacetum parthenium L. extract in mice and rats.

Oral administration of the feverfew (Tanacetum parthenium) extract led to significant antinociceptive and anti-inflammatory effects against acetic acid-induced writhing in mice and carrageenan-induced paw edema in rats, respectively. These responses were dose-dependent (10, 20, 40 mg/kg, p.o.). Parthenolide (1, 2 mg/kg i.p.), the active constituent of the extract also produced antinociceptive and anti-inflammatory effects. Naloxone (1 mg/kg i.p.), an opiate antagonist, failed to reverse feverfew extract and parthenolide-induced antinociception. Feverfew extract in higher doses (40, 60 mg/kg p.o.) neither altered the locomotor activity nor potentiated the pentobarbitone-induced sleep time in mice. It also did not change the rectal temperature in rats. Feverfew extract exerted antinociceptive and anti-inflammatory effects without altering the normal behaviour of the animals.

Is combined therapy of sympathomimetics and theophylline indicated?

Bronchodilator effect and toxicity of theophylline 300 mg twice a day (R1), salbutamol 4 mg tid (R2), their combination in higher (200/4mg, R3), and lower doses (100/2mg R4), and placebo (calcium lactate 300 mg) tid (R5) were compared in 25 patients with bronchial asthma in a randomized crossover trial. Statistically significant improvement in forced expiratory volume in one second (FEV1) was observed in all the active treatment groups (R1 to R4) compared with placebo (R5). The mean improvement in FEV1 was 29.0%, 22.0%, 28.0%, 30.0%, and 0.73% in regimen R1, R2, R3, R4, and R5, respectively day 1, and corresponding improvement was 30.0%, 24.0%, 29.0%, 34.0%, and 4.4% on completion of one week therapy. On intergroup statistical comparison, mean improvement in pulmonary function test values were statistically significant or highly significant in regimens R1 to R4, as compared with placebo. However, improvement between any two regimens was not statistically significant in any of the regimens (R1-R4). Almost all the regimens were tolerated well and no patient showed major adverse reactions or cardiotoxicity necessitating withdrawal of the drug. On the other hand, minor adverse reactions were common and the high dose combination (R3) was found to have more adverse reactions than the low dose combination and either drug used alone.