Foam-Based Drug Delivery: A Newer Approach for Pharmaceutical Dosage Form.

Foam is a dispersal of gas in solid foam or liquid foam. Solid foams are generally formed through quick curing of liquid foams. Because of their positive characteristics, simplicity of application, and improved patient acceptability/compliance, foams are an appealing and promising delivery strategy for medical, cosmetic, and pharmaceutical, applications. Recent breakthroughs in topical foams for cosmetic and dermal applications are described here, as well as categorization based on foam formulation and recent assessment techniques of critical physical properties of the topical foam. Despite the expanding amount of knowledge on topical foams for cutaneous applications, the majority of research has focused on the stability and structure of foam in contact with solid nonporous surfaces. It is still difficult to figure out how such foams destabilize when they come into touch with porous surfaces like skin or skin-like membranes. The foam-covered wide surface area and easily applied to the affected area. This type of delivery system also eliminates the chance of secondary infection that is associated with ointment and creams, which need to be applied to the affected area with help of fingers or an applicator.

Effect of processing methods on xylitol-starch base co-processed adjuvant for orally disintegrating tablet application.

Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.

Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits.

BACKGROUND: Various extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits. METHODS: Asiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model. RESULTS: The results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits' skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected. CONCLUSION: The asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

PVA-PEG physically cross-linked hydrogel film as a wound dressing: experimental design and optimization.

The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze-thaw method. Response surface methodology with Box-Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze-thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12 hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze-thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.

Polymeric behavior evaluation of PVP K30-poloxamer binary carrier for solid dispersed nisoldipine by experimental design.

CONTEXT: High melting point polymeric carrier without plasticizer is unacceptable for solid dispersion (SD) by melting method. Combined polymer-plasticizer carrier significantly affects drug solubility and tableting property of SD. OBJECTIVE: To evaluate and optimize the combined effect of a binary carrier consisting PVP K30 and poloxamer 188, on nisoldipine solubility and tensile strength of amorphous SD compact (SDcompact) by experimental design. MATERIALS AND METHODS: SD of nisoldpine (SDnisol) was prepared by melt mixing with different PVP K30 and poloxamer amount. A 32 factorial design was employed using nisoldipine solubility and tensile strength of SDcompact as response variables. Statistical optimization by design expert software, and SDnisol characterization using ATR FTIR, DSC and microscopy were done. RESULTS: PVP K30:poloxamer, at a ratio of 3.73:6.63, was selected as the optimized combination of binary polymeric carrier resulting nisoldipine solubility of 115 µg/mL and tensile strength of 1.19 N/m2. DISCUSSION: PVP K30 had significant positive effect on both responses. Increase in poloxamer concentration after a certain level decreased nisoldipine solubility and tensile strength of SDcompact. CONCLUSION: An optimized PVP K30-poloxamer binary composition for SD carrier was developed. Tensile strength of SDcompact can be considered as a response for experimental design to optimize SD.

Safety profiling of pioglitazone and telmisartan combination by sub-chronic toxicity study in rat.

It has been reported that the major cause of mortality in diabetes is cardiovascular diseases and contribution of hypertension is significant in this context. Pioglitazone, a thiazolidinedione class of therapeutic agent is used to treat type 2 diabetes mellitus. Telmisartan, an angiotensin receptor blocker antihypertensive has been reported to have beneficial effect if co-administered with pioglitazone for the management of diabetes complications. The present research work aims to evaluate the safety/toxicity profile of this combination in rat model. The investigation was carried out after co-administering the drugs to the rats for 28 days at three dose levels of 50, 100 and 150 mg/kg covering low to high dose ranges. Various hematological and biochemical parameters were studied in addition to the histopathology of the major organs in order to evaluate the toxicity profile of the combination. Absence of mortality and histopathological changes as well as unaltered hematological and biochemical parameters was observed. This preliminary investigation concludes that the combination of pioglitazone and telmisartan can primarily be stated as safe in animals, even at the dose level which is several folds higher than the intended human dose. Thus, this combination can be explored in future to develop a rational therapy regimen to treat hypertensive diabetic patients.

A novel one-dimensional thiocyanate-bridged cobalt(III) complex: synthesis, crystal structure characterization and Hirshfeld surface analysis.

A new one-dimensional thiocyanate-bridged cobalt(III) Schiff base complex, namely, catena-poly[[[4-bromo-2-((Z)-{[2-(thiophen-2-yl)ethyl]imino}methyl)phenolato-κ2N,O]cobalt(III)]-µ-thiocyanato-κ2N:S], [Co(SCN)(C13H11BrNOS)2]n or [Co(µ1,3-SCN)L2]n (1), where HL is 4-bromo-2-((Z)-{[2-(thiophene-2-yl)ethyl]imino}methyl)phenol, a bidentate Schiff base prepared from the condensation reaction of 5-bromosalicylaldehyde and 2-(thiophen-2-yl)ethylamine, has been synthesized by stirring Co(ClO4)2·6H2O, the Schiff base HL and ammonium thiocyanate (in a 1:2:1 molar ratio) in ethanol medium. The complex was characterized by FT-IR, electronic spectra and single-crystal X-ray diffraction (SC-XRD) studies. The SC-XRD data suggest that the compound crystallizes in the orthorhombic space group Pca21. The CoIII ion in 1 adopts a distorted octahedral geometry, the metal sites being six-coordinated by one thiocyanate N atom and one thiocyanate S atom in apical positions, and by two imine N atoms and two phenolate O atoms from two anionic L- ligands which form the basal plane. The thiocyanate ligand acts as a µ-1,3 bridge, joining neighbouring CoIII atoms and forming a uniform zigzag one-dimensional polymeric chain. The crystallographic data were also used in the Hirshfeld surface (HS) analysis, which aimed to investigate the nature and quantitative significance of any noncovalent intermolecular interactions inside the crystal lattice. The crystal void parameters have also been computed and show the molecules to be tightly packed.

Preservatives in Pharmaceuticals: Are They Really Safe?

Preservatives are the ingredients that are utilized in order to improve the shelf life of products (Medicines, food). These tend to slow down or stop the degradation or decomposition processes, therefore, enhance the shelf life of the products. These agents either interfere with the chemical reaction or check the growth of microorganisms in the products. Preservatives are classified according to the mode of action or source or chemical nature. The preservation efficacy can be affected by various factors, e.g., interaction with other components, nature of preservatives, type of containers, type of micro-organism, and pH. Despite being vital for various types of products, these chemicals are not safe, if not used appropriately. The review will provide an updated detail of different types of preservatives along with their safety aspect. This review also highlighted the maximum safe concentration of preservatives that can be required to develop a formulation with maximum safety and low toxicity.

Novel Formulation Approaches used for the Management of Osteoarthritis: A Recent Review.

BACKGROUND: Osteoarthritis (OA) causes economic, social, and health difficulties in patients. Approximately 10% to 15% of all persons above the age of 60 have some degree of OA. OA is more common in women than in males. Diagnosed OA prevalence varies widely among EU member states, from 2.8% in Romania to 18.3% in Hungary. INTRODUCTION: Osteoarthritis (OA) is a slow-progressing, non-inflammatory disorder. This disorder ultimately destroys articular cartilage and other joint components. The main symptoms are stiffness, pain, loss of flexibility, swelling, and bone spurs. Many modifiable and non-modifiable risk factors have been associated with osteoarthritis (OA), including obesity and lack of exercise, genetic susceptibility, bone density, work-related damage, and trauma. METHODS: Hydrogels, micro and nano-sized particles, and novel topical gels are the most common examples. Hydrogels are cross-linked polymers with 3-D architecture that can hold water and expand like living tissue. The micro-carriers and nano-based drug delivery systems provide several advantages and may demonstrate prolonged release, controlled release, and higher joint half-life. RESULTS: OA-induced male Lewis rats were injected with celecoxib-loaded PEA microspheres to assess in vivo biocompatibility and degradation. According to the findings of this research, PEA microspheres loaded with celecoxib may be employed as safe delivery of drugs with self-regulating behavior for pain treatment related to knee osteoarthritis. CONCLUSION: The concept of novel drug delivery systems has shown tangible benefits as a new avenue for precise, safe, high-quality drug delivery for OA treatment. Currently, herbal drugs are also used in osteoarthritis treatment due to their potency and fewer side effects than synthetic drugs. The herbosynthetic approach is a new concept for the delivery of both herbal and synthetic drugs together to exploit their individual beneficial effects while reducing undesirable side effects.

Derivatization, an Applicable Asset for Conventional HPLC Systems without MS Detection in Food and Miscellaneous Analysis.

One of the most valuable practices for analyzing not-so-analytical-friendly analytes in complex, heterogenous matrices is derivatization. Availability of numerous derivatizing reagents (DRs) makes the modification of analyte more exploitable in terms of an analytical perspective. A wide array of derivatization techniques like pre or post-column, in-situ, enzymatic, ultrasound-assisted, microwave-assisted, photochemical derivatization has added much-needed methodological strength in analyzing intricate analytical matrices (food, water, and soil). In recent years, analytical chemistry has achieved greater heights through the development of new sensitive methods with simple conventional instruments like High-Performance Liquid Chromatography (HPLC) devoid of Mass detectors. The prompt availability of these straightforward instruments also makes it a favorable option for routine analysis in food, environmental, bioanalytical chemistry. Analyzing food, environmental or bioanalytical specimen has some of the most problematic aspects, like the low concentration of the analytes accompanied by not too suitable analytical properties. Even though conventional HPLC lacks the required sensitivity but merger with derivatization can lead to a remarkable increase in sensitivity. In recent years there has been a lot of application of diverse derivatizations to increase the sensitivity and selectivity of the analyte for available instruments, resulting in notable findings. Therefore, this review describes the application of derivatization principles in the analysis of analytes in food and additional matrices using conventional HPLC instruments such as HPLC-UV, HPLC-DAD, and HPLC-FD. In this article, we will briefly review the different modes and multiple types of derivatizing reagents with their mechanisms and importance for encouraging the use of established HPLC instruments.

Development and In Vivo Evaluation of Pectin Based Enteric Coated Microparticles Loaded with Mesalamine and Saccharomyces boulardii for Management of Ulcerative Colitis.

Mesalamine is the first-line choice of drug for ulcerative colitis management. However, due to the nontargeted delivery of mesalamine, it shows side effects. The possible impact of mesalamine can be improved by coated microparticles in combination with S. boulardii for targeted delivery to the colon with the prevention of unwanted side effects. In this work, pectin-based mesalamine and S. boulardii loaded microparticles were prepared by dehydration technique and coated by an oil-in-oil solvent evaporation method and characterized by Scanning electron microscopy (SEM), X-ray diffraction, and zeta analysis. 2, 4, 6-Trinitrobenzenesulfonic acid was used for the induction of colitis. The anti-inflammatory effects of coated microparticles on Caco-2 cells were assessed by the determination of interleukin (IL)-8 concentration. In addition, the impact of coated microparticles on the concentration of colonic enzymes, including myeloperoxidase (MPO), lipid peroxides, and glutathione (GSH), were also evaluated. Moreover, hematological parameters, including white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were assessed. SEM data revealed that all the prepared coated microparticles had an almost spherical shape. The X-ray powder diffraction analysis of uncoated and coated microparticles showed maximum stability without any interaction. The particle size of uncoated and coated microparticles was 9.14 and 15.61 µm, respectively. The zeta potential of uncoated and coated microparticles was observed to be -26.78 and -29.36 mV, respectively. The prepared coated microparticles decreased the levels of lipid peroxides, MPO, and GSH significantly in colitis. In the Caco-2 cell culture model, the concentration of IL-8 is decreased significantly. The hematological observations confirmed that the prepared formulation showed a promising decrease in the levels of WBC, CRP, and ESR in diseased animals. Animal experiments revealed that cellulose acetate phthalate coated microparticles of mesalamine and S. boulardii significantly improved the colitis disease conditions of Wistar rats. Hence, cellulose acetate phthalate-coated microparticles of mesalamine and S. boulardii could be recommended as adjuvant therapy to achieve a synergistic effect in the management of UC. Lay summary Mesalamine is the drug of choice for the management of ulcerative colitis (UC), which inhibits mediators responsible for inflammation. We investigated the in vivo effects of cellulose acetate phthalate-coated microparticles of mesalamine with Saccharomyces boulardii (probiotic) for their efficacy against UC. Our findings evidenced that the combination of mesalamine with S. boulardii showed a synergistic effect in the 2,4,6- trinitrobenzene sulfonic acid-induced colitis model by reducing the inflammation and maintains the macroscopic features. From the observed results, it can be concluded that S. boulardii can be used to enhance the individual drug's effect in the therapeutic management of UC.

An Updated Account on Formulations and Strategies for the Treatment of Burn Infection - A Review.

BACKGROUND: Burn injury is considered one of the critical injuries of the skin. According to WHO (World Health Organization), approximately 3,00,000 deaths are caused each year mainly due to fire burns, with additional deaths attributed to heat and other causes of burn e.g., electric devices, chemical materials, radioactive rays, etc. More than 95% of burn injuries occur in developing countries. INTRODUCTION: Burn injuries have been a prominent topic of discussion in this present era of advancements. Burns is one of the common and devastating forms of trauma. Burn injuries are involved in causing severe damage to skin tissues and various other body parts triggered particularly by fire, blaze, or exposure to chemicals and heated substances. They leave a long-lasting negative impact on the patients in terms of their physical and mental health. METHODS: The various methods and bioactive hydrogels, a viable and widely utilised approach for treating chronic wounds, remain a bottleneck. Many traditional approaches such as woven material, conventional antimicrobial agents, hydrogel sheets, and creams are utilised in wound healing. Nowadays, lipid-based nanoparticles, nanofibres systems, and foam-based formulations heal the wound. RESULT: The prepared formulation showed wound healing activity when tested on rat model. The nanofibres containing SSD help in the burn-wound healing study on Male Sprague Dawley (SD) rats. The healing effect on rats was examined by western blot analysis, digital camera observation, and histological analyses. CONCLUSION: Burn is also considered the most grievous form of trauma. Nowadays, several large and foambased formulations are used in wound healing, which heals the wound better than previously existing formulations and is less prone to secondary infection. Recently, nanofiber delivery systems have piqued the interest of academics as well as researchers because of its unique advantages and features, which include an extraordinarily high surface to volume ratio, a highly porous structure, and tiny pore size.

A Recent Review On 3D-Printing: Scope and Challenges with Special Focus on Pharmaceutical Field.

BACKGROUND: The presentation of 3D printing in drug innovation especially focuses on the advancement of patient-centered dosage forms based on the structural design. Rising interest for customization of 3D printed inserts during surgeries combined with developing R&D speculations is driving the medical services. 3D printing technique is considered emerging digitized technology and it is beneficial for the future progression and development of customized dosage forms, prostheses, implantable medical devices, tissue making, disease modeling, and many more. 3D Printing technology has numerous benefits, such as minimum waste production, freedom of design, and the ability to make complex structures as well as rapid prototyping. METHODS: Various 3D printing techniques are utilized (such as drop on solid deposition, selective laser sintering/ melting, drop on drop deposition, stereolithography, fused deposition modeling, and pressure-assisted techniques) for the preparation of various pharmaceuticals, such as tablets, films, oral films, mouth guards, pellets, polyprintlets, catheters, etc. Results: With the help of various 3D printing techniques, researchers minimize dose frequency and side effects of drugs with the formation of multilayer tablets or polypills and benefit the person who is suffering from various diseases at a particular time. For example, multilayer polypills containing paracetamol, caffeine, naproxen, chloramphenicol, prednisolone, and aspirin. This study, most importantly, demonstrated the possibility of 3D printing for making diverse polypills to advance patient personalization with the help of the 3D printing technique. CONCLUSION: The authors hope this article will give a valuable boost to energize future researchers in the pharmaceutical field. Due to the novelty and particular highlights, 3D printing has the inborn ability to settle numerous formulation and medication conveyance challenges, which are often connected with poorly aqueous solubility. It has many unmet regulatory challenges that need to be addressed.

A Recent Review on Bio-availability Enhancement of Poorly Water-soluble Drugs by using Bioenhancer and Nanoparticulate Drug Delivery System.

BACKGROUND: Intravenous route of drug administration has maximum bioavailability, which shows 100% of the drug reaches blood circulation, whereas the oral administration of drugs, are readily undergoing pre-systemic metabolism, which means the poor bioavailability of the drug and limited amount of drug reaches the target site. INTRODUCTION: Bioenhancers are substances having medicinal entities which enhance the bioavailability and efficacy of the active constituents of drugs. The enhanced bioavailability of drugs may lead to dose reduction, which may further reduce the cost and undesired side effects associated with the drugs. METHODS: The solid lipid nanoparticles (SLNs) loaded with ketoprofen made from carnauba wax and beeswax. It was discovered that when the drug-loaded SLNs were mixed with egg-lecithin and Tween-80, as well as when the total surfactant concentration was increased, the average particle size of the drug-loaded SLNs decreased. RESULTS: The drug-loaded nanoparticles, when given in combination with bio-enhancers such as piperine and quercetin, enhanced the drug's effectiveness. The Area Under Curve (AUC) was increased when the drug was coupled with bio-enhancers. Based on the findings, it can be concluded that piperine and quercetin when used with drug-loaded nanoparticles improve their therapeutic effectiveness. CONCLUSION: Bioenhancers are crucial to amplifying the bioavailability of many synthetic drugs. These attributes are useful to reduce the dose of drugs and increase the therapeutic efficacy of drugs with poor bioavailability.

Review on perfume and present status of its associated allergens.

BACKGROUND: Perfume is basically a cosmetic product applied to human body for an amusing scent or the feeling of freshness. A certain amount of perfume penetrates and remains attached to the protein of the skin when perfume is applied on the body. It evokes a surge of events in human immune system which results with allergic symptoms. Fragrance ingredients are leading cause that can be responsible for the occurrence of allergic contact dermatitis that is recently studied under cosmetic adverse reaction. AIM: The aim of this review article was to define the allergies that are caused by fragrance ingredients. This review highlights the various aspects of perfume with respect to its manufacturing process, compositions, and fragrance ingredients identified as allergens and its present regulatory status. METHOD: There area 175 frangrance ingredients that are used in perfumes cause allergic reaction. Several studies were conducted on the patients. The study was conducted on four fragrance markers in the baseline series: fragrance mix I (FM I), Myroxylon pereirae, fragrance mix II (FM II), and hydroxyisohexyl 3-cyclohexene carboxaldehyde. RESULT: Around 658 patients showed allergy due to fragrance ingredients when the patch test was performed. In other study, out of 1253 patients, 90% of the FM I and M. pereirae detected 90% of the cases. CONCLUSION: Majority of the fragrance ingredients can cause allergic reactions and hence act as allergens and thus increase the risk of sensitization on activation. If any individual suffers from allergy or contact dermatitis on use of any perfume, he/she should be aware of it and should reduce or avoid its use to overcome such problems of hypersensitivity.

Photocatalytic activity of Ni0.5Zn0.5Fe2O4@polyaniline decorated BiOCl for azo dye degradation under visible light - integrated role and degradation kinetics interpretation.

Herein, we demonstrated the excellent improvement in photocatalytic degradation performance of BiOCl upon facile heterogeneous decoration with an integrated Ni0.5Zn0.5Fe2O4@polyaniline nanocomposite for an organic pollutant, methyl orange dye (MO), under visible light irradiation. The physico-chemical nature of the heterogeneous nanocomposite was characterized by XRD, FTIR, HRTEM-EDX and XPS analyses. The tuning of the band gap and optical sensitivity of BiOCl using Ni0.5Zn0.5Fe2O4@polyaniline were measured by DRS, PL and EIS techniques. To validate the transformation of the BiOCl photocatalyst to a visible light active photocatalyst due to the incorporation of Ni0.5Zn0.5Fe2O4@polyaniline and to gain insight into the origin of the synergistic effect for dye degradation by the heterostructured nanocomposite, we explored the effects of process parameters such as catalyst dosage, initial dye concentration, pH and the presence of inorganic anions on the extent of photo degradation. To get more details about reaction kinetics, a kinetic model using non-liner regression analysis was developed and the validity of the model was tested by comparing the experimental values with the calculated data. Based on the intermediate product formation, identified by GC-MS, a probable degradation pathway and a mechanism based on the electrochemical behaviour of the developed catalyst and trapping experiments were also proposed.

Identified Hybrid tRNA Structure Genes in Archaeal Genome.

BACKGROUND: In Archaea, previous studies have revealed the presence of multiple intron-containing tRNAs and split tRNAs. The full unexpurgated analysis of archaeal tRNA genes remains a challenging task in the field of bioinformatics, because of the presence of various types of hidden tRNA genes in archaea. Here, we suggested a computational method that searched for widely separated genes encoding tRNA halves to generate suppressive variants of missing tRNAs. OBJECTIVES: The exploration of tRNA genes from a genome with varying hypotheses, among all three domain of life (eukaryotes, bacteria and archaea), has been rapidly identified in different ways in the field of bioinformatics. Like eukaryotic tRNA genes, it has been established that two separated regions of the coding sequence of a tRNA gene are essential and sufficient for promotion of transcription. Our objective is to find out the two essential regions in the genome sequence which comprises two halves of the hidden tRNAs. MATERIAL AND METHODS: Considering the existence of split tRNA genes widely separated throughout the genome, we developed our tRNA search algorithm to predict such separated tRNA genes by searching both a conserved terminal 5'- and 3'-motif of tRNA in agreement with the split hypothesis on the basis of cloverleaf prediction and precise insilico determination of bulge-helix-bulge secondary structure at the splice sites. RESULTS: By a comprehensive search for all kinds of missing tRNA genes, we have constructed hybrid tRNA genes containing one essential region from tDNA (XYZ) and the other from tDNA (ABC), both from same species in the archaea. We have also found, this type of hybrid tRNA genes are identified in the different species of the archaea (XYZ ASN, ARG and MET; ABC ASP,SER, ARG and PRO).These hybrid split tRNA share a common structural motif called bulge-helix-bulge (BHB) a more relaxed bulge-helix loop (BHL), at the leader exon boundary and suggested to be evolutionary interrelated. CONCLUSIONS: Analysis of the complete genome sequences of Metallosphaera sedula DSM 5348, Desulfurococcus kamchatkensis 1221n and Ignicoccus hospitalis KIN4/I in archaea by our algorithm revealed that a number of hybrid tRNAs are constructed from different tDNAs . Asymmetric combination of 5' and 3' tRNA halves may have generated the diversity of tRNA molecules. Our study of hybrid tRNA genes will provide a new molecular basis for upcoming tRNA studies.

Liquid Chromatography Based Methods for Analysis of Disease-Modifying Antirheumatic Drugs (DMARDs) in Biological Matrices.

Rheumatoid arthritis (RA) is a common chronic disease with inflammatory and immunological background where treatments can only improve the symptoms and slow down the progress of the disease. Although there are several drugs with different therapeutic targets available in the market for the treatment of RA, conventional synthetic disease-modifying antirheumatic drugs (DMARDs) are the most effective option to date. Methotrexate, azathioprine, hydroxychloroquine, sulfasalazine, leflunomide, minocycline are commonly prescribed DMARDs by rheumatologists but they have the limitations of severe toxicity for which therapeutic drug monitoring is necessary. Many chromatographic methods are available for analysis of these drugs including their metabolites. However, they have not been critically reviewed for pre-chromatographic sample preparation, chromatographic separation and sensitive detection. This review article can be handy for quantitation of DMARDs in diverse biological matrices as it provides comprehensive information on the reported liquid chromatographic methods for last three decades covering all the aspects required for preclinical and clinical studies.

Targeted drug delivery to the brain via intranasal nanoemulsion: Available proof of concept and existing challenges.

Intranasal delivery has shown to circumvent blood-brain-barrier (BBB) and deliver the drugs into the CNS at a higher rate and extent than other conventional routes. The mechanism of drug transport from nose-to-brain is not fully understood yet, but several neuronal pathways are considered to be involved. Intranasal nanoemulsion for brain targeting is investigated extensively. Higher brain distribution of drug after administering intranasal nanoemulsion was established by many researchers. Issues with nasomucosal clearance are solved by formulating modified nanoemulsion; for instance, mucoadhesive nanoemulsion or in situ nanoemulgel. However, no intranasal nanoemulsion for brain targeted drug delivery has been able to cross the way from 'benches to bed-side' of patients. Possibilities of toxicity by repeated administration, irregular nasal absorption during the diseased condition, use of a high amount of surfactants are few of the persisting challenges that need to overcome in coming days. Understanding the ways how current developments has solved some challenges is necessary. At the same time, the future direction of the research on intranasal nanoemulsion should be figured out based on existing challenges. This review is focused on the current developments of intranasal nanoemulsion with special emphasis on the existing challenges that would help to set future research direction.

Impact of carbon inputs on soil carbon fractionation, sequestration and biological responses under major nutrient management practices for rice-wheat cropping systems.

Major nutrient management systems for rice-wheat cropping were compared for their potential to credit organic carbon (C) to the soil, its fractionation into active (very labile, VLc; labile, Lc) and passive (less labile, LLc; non-labile, NLc) pools, and crop yield responses. A ten-year long experiment was used to study effects of: (i) no inputs (Control, O), (ii) 100% inorganic fertilizers (F) compared to reduced fertilizers inputs (55%) supplemented with biomass incorporation from (iii) opportunity legume crop (Vigna radiata) (LE), (iv) green manure (Sesbania aculeata) (GM), (v) farmyard manure (FYM), (vi) wheat stubble (WS), and (vii) rice stubble (RS). Maximum C input to soil (as the percentage of C assimilated in the system) was in GM (36%) followed by RS (34%), WS (33%), LE (24%), and FYM (21%) compared to O (15%) and F (15%). Total C input to soil had a direct effect on soil C stock, soil C fractions (maximum in VLc and LLc), yet the responses in terms of biological yield were controlled by the quality of the biomass (C:N ratio, decomposition, etc.) incorporated. Legume-based biomass inputs accrued most benefits for soil C sequestration and biological productivity.