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Glycyrrhetinic acid-modified chitosan (mGA-suc-CTS) is used as liver-targeted carrier for drug delivery. In this study, nanoparticles were prepared by ionic gelation process, and glycyrrhetinic acid act as the targeting ligand. The structure of the product was confirmed by IR and NMR techniques. The main aim of this study was to deliver atorvastatin directly to the liver by using same conjugate and reduce the associated side-effects, i.e. hepatotoxicity at high dose. Characterization of the developed formulation was performed by differential scanning calorimetry, particle size measurements and cellular uptake studies. Release profile, pharmacokinetics studies and organ distribution studies showed that developed formulation shows a relative higher liver uptake. The optimized formulation showed increased plasma concentration than the CTS nanoparticles as well as plain drug and the accumulation in the liver was nearly 2.59 times more than that of obtained with the CTS nanoparticles. Pharmaceutical and pharmacological indicators suggested that the proposed strategy can be successfully utilized for liver targeting of therapeutics.

Archaeosomes as liposomes made with one or more ether lipids that are unique to the domain of Archaeobacteria, found in Archaea constitute a novel family of liposome. Achaean-type lipids consist of archaeol (diether) and/or caldarchaeol (tetraether) core structures. Archaeosomes can be produced using standard procedures (hydrated film submitted to sonication, extrusion and detergent dialysis) at any temperature in the physiological range or lower, therefore making it possible to encapsulate thermally stable compounds. Various physiological as well as environmental factors affect its stability. Archaeosomes are widely used as drug delivery systems for cancer vaccines, Chagas disease, proteins and peptides, gene delivery, antigen delivery and delivery of natural antioxidant compounds. In this review article, our major aim was to explore the applications of this new carrier system in pharmaceutical field.

Psoriasis is a chronic disorder with erythematous scaly patches, which typically affects the exposed surfaces of the body and scalp. Various factors such as bacterial infection, genetic and environmental factors, and immune disorders play an important role in causing psoriasis. Different types of psoriasis can be observed, such as guttate psoriasis, inverse psoriasis, pustular psoriasis, and psoriatic arthritis. Various ancient, topical, and systemic approaches have been used to control the disease, but have failed to achieve a complete reduction of the disease, besides causing toxic effects. Therefore, our main aim in this review article is to introduce the different advanced nanotechnological approaches for effective treatment of psoriasis.

The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.

Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endothelium dysfunction, we measured endothelial markers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70- to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes., (© 2016 by the American Diabetes Association.)

The objective of the current investigation was to develop a novel biocomposite polymeric nanofiber for sublingual delivery of nicorandil in an attempt to reduce mucosal ulceration and to improve drug bioavailability. Polymeric nanofibers were achieved using vitamin B12 and a blend of hyaluronic acid and polyvinyl alcohol as polymeric constituents. The electrospinning method was used to prepare drug (nicorandil)-loaded nanofibers. The resulting nanofibers were characterized for morphology, drug loading, XRD, DSC, in vitro drug release, degree of swelling, and pharmacokinetic behavior. The prepared nanofibers were found to be uniform, non-beaded, and non-woven, with fiber diameter ranging from 200-450 nm. In vitro drug release substantiated the controlled release behavior of the developed formulation. Histopathology studies demonstrated no evidence of mucosal ulceration at the site of application. Pharmacokinetic studies established the preclinical safety and showed the maintenance of an effective therapeutic level for a prolonged period. The present investigation gives inputs showing that the biocomposite nanofiber assists as a perfect carrier system for sublingual delivery of anti-anginal drugs.

In the present study, nanostructured lipid carriers (NLCs) along with various surfactants loaded with paclitaxel (PTX) were prepared by an emulsification technique using a Box-Behnken design. The Box-Behnken design indicated that the most effective factors on the size and PDI were at high surfactant concentration (1.5%), low lipids ratio (6:4) and medium homogenization speed (6000 rpm). Among all the formulations, Tween 20-loaded NLCs show least particle size compared to Tween 80 and Tween 60. Entrapment efficiency of Tween 20, Tween 80 and Tween 60-loaded formulations were 82.40, 85.60 and 79.78%, respectively. Drug release of Tween 80, Tween 20 and Tween 60-loaded NLCs is 64.9, 62.3 and 59.7%, respectively (within 72 h). Maximum cellular uptake was observed with Tween 20 formulation on Caco-2 cell lines. Furthermore, spray drying of resultant NLCs was showed good flow properties and was selected for drug delivery to deeper airways. In-vivo studies demonstrated the better localization of drug within the lungs using different surfactant-based pulmonary delivery systems. From this study, we have concluded that delivering drugs through pulmonary route is advantageous for local action in lungs as maximum amount of drug concentration was observed in lungs. The surfactants could prove to be beneficial in treating drug resistance lung cancer by inhibiting P-gp efflux in the form of nano lipidic carriers.

Activation of peroxisome proliferator-activated receptor-β/δ (PPARβ) lowers blood pressure in genetic and mineralocorticoid-induced hypertension. Regulator of G-protein-coupled receptor signaling 5 (RGS5) protein, which interferes in angiotensin II (AngII) signaling, is a target gene to PPARβ The aim of the present study was to examine whether PPARβ activation in resistance arteries and brain tissues prevents the elevated blood pressure in AngII-induced hypertension and evaluate the role of RGS5 in this effect. C57BL/6J male mice were divided into five groups (control mice, PPARβ agonist [4-[[[2-[3-Fluoro-4-(trifluoromethyl)phenyl]-4-methyl-5-thiazolyl]methyl]thio]-2-methylphenoxy]acetic acid (GW0742)-treated mice AngII-infused mice, GW0742-treated AngII-infused mice, and AngII-infused mice treated with GW0742 plus PPARβ antagonist 3-[[[2-Methoxy-4-(phenylamino)phenyl]amino]sulfonyl]-2-thiophenecarboxylic acid methyl ester (GSK0660)) and were followed for 3 weeks. GW0742 prevented the increase in both arterial blood pressure and plasma noradrenaline levels and the higher reduction of blood pressure after ganglionic blockade, whereas it reduced the mesenteric arterial remodeling and the hyper-responsiveness to vasoconstrictors (AngII and endothelin-1) in AngII-infused mice. These effects were accompanied by an inhibition of NADPH oxidase expression and activity in the brain. Gene expression profiling revealed a marked loss of brainstem and vascular RGS5 in AngII-infused mice, which was restored by GW0742. GW0742-induced effects were abolished by GSK0660. Small interfering RNA targeting RGS5 caused augmented contractile response to AngII in resistance mesenteric arteries and blunted the inhibitory effect of GW0742 on this response. In conclusion, GW0742 exerted antihypertensive effects, restoring sympathetic tone and vascular structure and function in AngII-infused mice by PPARβ activation in brain and vessels inhibiting AngII signaling as a result of RGS5 upregulation., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)

Recently, sustained and controlled drug delivery has become the demand, and research has been undertaken in achieving much better drug product effectiveness, reliability and safety. The in situ polymeric system has gained much attention, to develop a controlled release system. It has been used as a vehicle for local and systemic drug delivery. Nowadays, it has created much interest, because of its characteristics of high vascularization, high permeability, rapid onset of action, low enzymatic degradation, and avoidance of hepatic first pass metabolism. The main aim of this review is to provide knowledge of different mechanisms of nasal absorption and approaches for nasal drug delivery.

From the early sixteenth and seventeenth centuries to the present day of life, tuberculosis (TB) still is a global health threat with some new emergence of resistance. This type of emergence poses a vital challenge to control TB cases across the world. Mortality and morbidity rates are high due to this new face of TB. The newer nanotechnology-based drug-delivery approaches involving micro-metric and nano-metric carriers are much needed at this stage. These delivery systems would provide more advantages over conventional systems of treatment by producing enhanced therapeutic efficacy, uniform distribution of drug molecule to the target site, sustained and controlled release of drug molecules and lesser side effects. The main aim to develop these novel drug-delivery systems is to improve the patient compliance and reduce therapy time. This article reviews and elaborates the new concepts and drug-delivery approaches for the treatment of TB involving solid-lipid particulate drug-delivery systems (solid-lipid micro- and nanoparticles, nanostructured lipid carriers), vesicular drug-delivery systems (liposomes, niosomes and liposphere), emulsion-based drug-delivery systems (micro and nanoemulsion) and some other novel drug-delivery systems for the effective treatment of tuberculosis and role of immunomodulators as an adjuvant therapy for management of MDR-TB and XDR-TB.

Microemulsions have gained significant attention from formulation scientists since the time they have been discovered, because of their excellent properties related to their stability, solubility, simplicity, and formulation aspects. The application of microemulsions is not limited to drug delivery via the oral, topical or ocular routes, but may also be seen in cosmetics, immunology, sensor devices, coating, textiles, analytical chemistry, and spermicide. Finally, the objective of this review is to discuss briefly the applications of microemulsions in advanced drug delivery.

The main object of this current research was to examine transferosomes as a transdermal delivery system for insulin, to overwhelm the difficulties related with its subcutaneous delivery. Transferosomal gel formulations were prepared by rotary evaporation sonication technique. The result revealed that insulin was successfully entrapped (78%) in optimized formulations (2.5 I.U. of the drug and 25% of sodium cholate) with cumulative percent drug release (83.11 ± 3.782). The glucose lowering study revealed that the transferosomal gel with chemical penetration enhancer showed better glucose lowering effect as compared to the control gel. Consequently, this study authenticated that the transferosomal gel can be used as a possible substitute to the conventional formulations of insulin with progressive permeation characteristics for transdermal application.

The liver is a vital organ present in vertebrates, which performs many functions including detoxification, protein synthesis and production of various bio-chemicals which are very important for digestion. A large number of serious liver disorders affect millions of people worldwide which are very difficult to treat properly despite many efforts. There are several factors which are responsible for liver injuries, include plants (Crotalaria Senecio Heliotropium Symphytum officinale), drugs (analgesic and antibiotics), industrial toxins (mercury and lead), water, alcohol and so on. Herbal medicinal preparations can be used for the treatment of a large number of human liver disorders like cirrhosis, hepatitis, carcinomas, etc. Indian Medicinal Practitioner's Co-operative pharmacy and Stores (IMPCPS) approved herbal-based systems (Unani, Siddha and Ayurveda) for the treatment of various chronic liver disorders. Different types of the receptors are found on the surface of hepatocytes, Kupffer cell, hepatic stellate cell and sinusoidal endothelial cells, etc., which can be used for achieving liver targeting. These receptors bind to different types of ligands (galactosylated, lactobionic acid, asialofetuin, etc.) which can be used in the formulation to achieve targeted delivery of the drug. Various novel particulate approaches (liposomes, niosomes, nanoparticles, micelles, nanosuspensions, etc.) can be used to enhance the targeting efficiency of systems to receptors found on the surface of different cells present in the liver. In this review, we focused on the status of liver targeting via herbal and nanotechnology inspired formulation approaches.

The purpose of this research is to describe the utility of nanofibers as a gastroretentive dosage form and improve the solubility of diacerein (DIA) by using the above approach. Poly L-(lactic acid) (PLLA) nanofibers loaded with DIA were prepared using the electrospinning technique. The nanofibers developed were characterized for morphology, tensile strength, floating behavior, drug entrapment, drug solubility, mucoadhesive detachment force, and drug release profile. The results demonstrated that the drug-loaded nanofibers were smooth, discrete, & non-woven. Analysis by X-ray crystallography (XRD) revealed that the drug in the nanofiber was present in the amorphous state, which largely contributes to higher drug solubility in the nanofibers developed. The buoyancy study demonstrated that the nanofibers developed exhibited zero lag time. Approximately 61.3% of drug was released in 30 h, thus facilitating the slow release of the drug from the nanofiber system. Finally, we concluded that the electrospun nanofibers developed offer a promising gastroretentive drug delivery system to deliver DIA with improved solubility.

The aim of this study was to prepare and characterize spray dried inhalable chitosan nanoparticles (CNPs) for sustained delivery of anti-tubercular drugs, isoniazid (INH) and rifampicin (RIF), to the lungs. CNPs were prepared by ionic gelation technique followed spray drying. Results showed that the CNPs obtained had a smooth spherical shape with an average size of 230 ± 4.5 nm, with a poly dispersity index of 0.180 ± 0.021. Both drugs, were detected in various organs (lungs, liver, spleen and kidney) until 24 h post nebulization. The chemotherapeutic efficacy of a single dose of drug-loaded CNPs suggested that they are more effective against the mycobacterium than free drugs.

The objective of this study was to develop an oral transmucosal formulation of an antiemetic drug that can not only serve in the active form but also provide a controlled release profile. In this study, sublingual films based on the biodegradable and water-soluble polymers, that is HPMCK-4M and PVPK-30, were developed by the solvent casting method, and were loaded with the antiemetic drug granisetron hydrochloride (granisetron HCl). The entrapment efficiency of the developed formulation was found to be 86%. The in vitro profile showed an instant release of the drug from the sublingual film, in a pattern following the first order kinetics array. The in vivo studies showed that granisetron HCl was delivered in its active state and showed effective results, as compared to its activity in the marketed formulation.

The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

Endothelial dysfunction is considered to be an early event in atherosclerosis and plays a pivotal role in the development, progression and clinical complications of atherosclerosis. Previous studies have shown the beneficial effects of combined inhibition of thromboxane synthase and antagonism of thromboxane receptors by BM-573 on atherosclerosis; however our knowledge about the beneficial effects of BM-573 on endothelial function and increased blood pressure related to early stage of atherosclerosis is limited. In the present study, we investigated the effects of short-term (3 μM, 1 hour) and chronic (10 mg/L, 8 weeks) treatments with BM-573 on vasodilatory function, nitric oxide (NO) bioavailability, oxidative stress and systolic blood pressure in 15 weeks old apolipoprotein E-deficient (ApoE-KO) mice. ApoE-KO mice showed a reduced endothelium-derived relaxation. In addition, NO bioavailability was reduced and oxidative stress and blood pressure were increased in ApoE-KO mice versus wild-type mice. BM-573 treatments were able to improve the relaxation profile in ApoE-KO mice. Short-term effects of BM-573 were mainly mediated by an increased phosphorylation of both eNOS and Akt, whereas BM-573 in vivo treatment also reduced oxidative stress and restored NO bioavailability. In addition, chronic administration of BM-573 reduced systolic blood pressure in ApoE-KO mice. In conclusion, pharmacological modulation of TxA2 biosynthesis and biological activities by dual TP antagonism/TxAS inhibition with BM-573, already known to prevent plaque formation, has the potential to correct vasodilatory dysfunction at the early stages of atherosclerosis.

The major goal of the current research was to develop and evaluate the therapeutic potential of anti-tubercular drugs (ATDs) loaded natural polysaccharide comprising of galacto mannan subunit in experimental tuberculosis (TB). Experimental formulations were prepared by ionotropic gelation technique followed by spray drying. Morphological analysis suggested that optimized nanoparticles were found to be discrete and spherical in nature with a particle size distribution range from 230 ± 4.5 nm to 310 ± 6.2 nm. The in-vitro drug release behavior indicated the biphasic pattern comprising of initial burst followed by a sustained release pattern. Guar gum coated chitosan nanoparticles (CGNPs) among the leading formulation exhibited the highest cell uptake potential confirmed by FACS analysis. Challenge study also supports the in-vivo bio-distribution illustrated by the significant reduction in CFU count in experimental TB in mice. Histopathology study demonstrated that none of the treated group shows any evidence of lung tissue abnormality. Hence, the study marked the fact that CGNPs could be a promising carrier for selective delivery of ATDs to alveolar macrophages for efficient management of TB with the interception of minimal side effects.

Background: The pathophysiology of preeclampsia is not clearly understood worldwide. Hypoxia inducible factor 1α (HIF-1α) is thought to be the preliminary factor for the hypoxic conditions prevailing in preeclampsia, which causes imbalance in the expression of angiogenic proteins. A proangiogenic protein, placental growth factor (PIGF), is reported to be dysregulated in preeclampsia. Therefore, this study focuses on the investigation of HIF-1α and PIGF in preeclamptic conditions and a possible molecular association between them., Methods: Placental tissue (n = 45 + 45) and serum samples (n = 80 + 80) of preeclamptic patients and healthy control were collected and processed for the analysis of HIF-1α and PIGF by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA)., Results: In preeclamptic group, the significant nuclear and cytoplasmic expression of HIF-1α was noticed in syncytiotrophoblast (P = 0.0001) but in control placenta, it was localized to cytoplasm (P = 0.0001). The intensity of PIGF expression was lower in syncytiotrophoblast cytoplasm (P = 0.0001) in preeclamptic cases as compared with control. Also, the significant upregulated concentration of HIF-1α and downregulated PIGF was observed in serum samples of preeclamptic woman (P = 0.0001). Thus, there was a significant direct negative correlation between HIF-1α and PIGF both at tissue and serum level (P < 0.01)., Conclusion: The direct inverse association between HIF-1α and PIGF in serum and placental tissues may be responsible for the low oxidative stress and endothelial dysfunction, leading to the pathogenesis of preeclampsia., (© 2014 Wiley Periodicals, Inc.)

Background: Cervical cancer is the most frequently diagnosed cancer among women in India. Understanding quality of life (QOL) in women undergoing chemoradiotherapy for cervical cancer will help in introducing interventions for better care and outcomes in these women. This study assessed QOL before and after chemo radiotherapy in cervical cancer patients., Materials and Methods: This followup study covered sixtyseven newly diagnosed women with advanced cervical cancer (stages 2b to 4b). Structured questionnaires (the European Organization for Research and Treatment of Cancer, EORTC QLQC30 and EORTC QLQCX24) were used to assess the change in QOL after 6 months of treatment., Results: The mean age of women at the time of detection of cervical cancer was 52.3±11.29 years (Range 3075 years). Six months survival was 92.53%. The mean global health score of cervical cancer patients after six months of treatment was 59.52, which was significantly higher than the pretreatment score of 50.15 (p=0.00007). Physical, cognitive and emotional functioning improved significantly (p<0.05) after treatment. Fatigue, pain, insomnia and appetite loss improved but episodes of diarrhea increased after treatment. The mean "symptoms score" using EORTC QLQCX24 post treatment was 20.0 which was significantly lower as compared to the pre treatment score 30.0 (p<0.00001). Sexual enjoyment and sexual functioning decreased significantly after treatment., Conclusions: QOL of newly diagnosed cervical cancer patients improved significantly following chemoradio therapy. Enhancement was also demonstrated on three of the five functional scales of EORTC QLQC30. To further improve QOL, interventions focusing on social and psychological support and physical rehabilitation may be needed.

Background: Tobacco use is the single most important preventable risk factor for cancer. Surveillance of tobacco-related cancers (TRC) is critical for monitoring trends and evaluating tobacco control programmes. We analysed the trends of TRC and evaluated the population-based cancer registry (PBCR) in Delhi for simplicity, comparability, validity, timeliness and representativeness., Materials and Methods: We interviewed key informants, observed registry processes and analysed the PBCR dataset for the period 1988-2009 using the 2009 TRC definition of the International Agency for Research on Cancer. We calculated the percentages of morphologically verified cancers, death certificate-only (DCO) cases, missing values of key variables and the time between cancer diagnosis and registration or publication for the year 2009., Results: The number of new cancer cases increased from 5,854 to 15,244 (160%) during 1988-2009. TRC constituted 58% of all cancers among men and 47% among women in 2009. The age-adjusted incidence rates of TRC per 100,000 population increased from 64.2 to 97.3 among men, and from 66.2 to 69.2 among women during 1988-2009. Data on all cancer cases presenting at all major government and private health facilities are actively collected by the PBCR staff using standard paper-based forms. Data abstraction and coding is conducted manually following ICD-10 classifications. Eighty per cent of cases were morphologically verified and 1% were identified by death certificate only. Less than 1% of key variables had missing values. The median time to registration and publishing was 13 and 32 months, respectively., Conclusions: The burden of TRC in Delhi is high and increasing. The Delhi PBCR is well organized and generates high-quality, representative data. However, data could be published earlier if paper-based data are replaced by electronic data abstraction.

This study aims to prepare spray-dried inhalable powders containing anti-tubercular drugs-loaded HPMC nanoaggregates for sustained delivery of drugs to the lung. Nanoaggregates were prepared by precipitation technique. Results showed that the powders obtained had excellent aerosolization property. High drug encapsulation efficiency was achieved in HPMC nano aggregates, ranging from 60% to 70%. A single pulmonary dose resulted in therapeutic drug concentrations 40% to 60% in the lungs and in other organs (< 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs.

Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

The present study is designed to explore the localized delivery of fluconazole using mucoadhesive polymeric nanofibers. Drug-loaded polymeric nanofibers were fabricated by the electrospinning method using polyvinyl alcohol (PVA) as the polymeric constituent. The prepared nanofibers were found to be uniform, non-beaded and non-woven, with the diameter of the fibers ranging from 150 to 180 nm. Further drug release studies indicate a sustained release of fluconazole over a period of 6 h. The results of studies on anti-microbial activity indicated that drug-loaded polymeric nanofibers exhibit superior anti-microbial activity against Candida albicans, when compared to the plain drug.

Electrospun nanofibers showing great promise for fabricating nanostructured materials might help to improve the quality of wound care. The present study aimed to investigate the wound-healing potential of collagen nanofiber mats containing silver nanoparticles. Silver nanoparticles (AgNPs) synthesized by the chemical reduction method were incorporated in collagen nanofibers during the electrospinning process. Characterization of electrospun nanofiber mats revealed a mean fiber diameters in the range of 300-700 nm with a sustained release of silver ions shown to follow pseudo-order kinetics. MIC of AgNPs against Staphylococcus aureus and Pseudomonas aeruginosa were evaluated using micro-dilution assay and further antimicrobial activity of fabricated nanofibers was performed. Finally, in vivo studies were performed to demonstrate the wound-healing efficacy of composite nanofibers. In vitro results confirmed the potential antimicrobial efficacy provided by AgNPs and AgNPs composite nanofibers, essential to provide an aseptic environment at the wound site. In vivo study revealed that the rate of wound healing of the composite nanofiber mats was found to be accelerated compared with plain collagen nanofibers. Histology analysis revealed an accelerated re-epithelization, collagen production, and better wound contraction with AgNPs composite collagen nanofibers.

Systemic antibiotic therapy in post-operative wound care remain controversial leading to escalation in levels of multi-resistant bacteria with unwanted morbidity and mortality. Recently zinc (Zn) because of multiple biophysiological functions, gain considerable interest for wound care. Based on our current understanding, the present study was designed with an intent to produce improve therapeutic approaches for post-operative wound management using composite multi-functional antibiotic carrier. The study involved the fabrication, characterization and pre-clinical evaluation of cefazolin nanofiber mats loaded with zinc oxide (ZnO) and comparing co-formulated mats with individual component, enable a side by side comparison of the benefits of our intervention. Minimum inhibitory concentration (MIC) of the drug, ZnO nanoparticles (ZnONPs) and drug-ZnONP mixture against Staphylococcus aureus was determined using micro dilution assay. The fabricated nanofibers were then evaluated for in-vitro antimicrobial activity and the mechanism of inhibition was predicted by scanning electron microscopy (SEM). Further these nanofiber mats were evaluated in-vivo for wound healing efficacy in Wistar rats. Study revealed that the average diameter of the nanofibers is around 200-900 nm with high entrapment efficiency and display sustained drug release behavior. The combination of ZnO and cefazolin in 1:1 weight ratio showed higher anti-bacterial activity of 1.9 ± 0.2 μg/ml. Transmission electron microscopy of bacterial cells taken from the zone of inhibition revealed the phenomenon of cell lysis in tested combination related to cell wall disruption. Further composite medicated nanofiber mats showed an accelerated wound healing as compared to plain cefazolin and ZnONP loaded mats. Macroscopical and histological evaluations demonstrated that ZnONP hybrid cefazolin nanofiber showed enhanced cell adhesion, epithelial migration, leading to faster and more efficient collagen synthesis. Hence the fabricated composite nanofiber mats have the potential to be used as a postoperative antimicrobial wound dressings., (Copyright © 2015. Published by Elsevier B.V.)

Background: Breast cancer is by far the most frequent cancer of women (23% of all cancers), ranking second overall when both sexes are considered together. Since there has been change in clinico-pathological factors and treatment profiles for breast cancer patients over the years, the present study to evaluate the change trends in India., Materials and Methods: A detailed analysis was carried out with respect to age, menopausal status, family history, disease stage, surgery performed, histopathology, hormone receptor status, and use of chemotherapy or hormonal therapy. Change in various clinico-pathological factors and treatments of breast cancer cases was recorded and analysed., Results: Mean age at presentation was found to be earlier in 2005-2006 compared with 1997-98 (p value: 0.046). More premenopausal women were diagnosed with breast cancer in 2005-2006 when this was compared with initial years of assessment (p value ≤0.001). When change in the receptor status was evaluated, we observed that there was a decrease in cases of ER and PR receptor positivity which was significant (p value: 0.007). Over the period of time, more f patients were not offered surgery initially in view of advanced disease when the two time periods were compared (p value: ≤0.001). There was a significant increase in patients who were initially offered neo-adjuvant chemotherapy in view of advanced disease at presentation (p value: ≤0.001). There was increasing number of patients who received palliative treatment for symptoms in 2005-2006 when compared to patients treated in 1997-98((p value: ≤0.001)., Conclusions: Changes in mean age at presentation, premenopausal status, and stage at presentation have occurred over the years. More aggressive patterns of disease have become more common with early age at presentation and aggressive biological behaviour with receptor negative tumours.

The main object of the self-emulsifying drug-delivery system (SEDDS) is oral bioavailability (BA) enhancement of a poorly water-soluble drug. Low aqueous solubility and low oral BA are major concerns for formulation scientists. As many drugs are lipophilic in nature, their lower solubility and dissolution are major drawbacks for their successful formulation into oral dosage forms. More than 60% of drugs have a lipophilic nature and exhibit poor aqueous solubility. Various strategies are reported in the literature to improve the solubility and enhance BA of lipophilic drugs, including the formation of a cyclodextrin complex, solid dispersions, and micronization. SEDDSs are ideally isotropic mixtures of drug, oil, surfactant, and/or cosurfactant. SEDDSs have gained increasing attention for enhancing oral BA and reducing drug dose. SEDDSs also provide an effective and excellent solution to the various issues related to the formulation of hydrophobic drugs that have limited solubility in gastrointestinal fluid. Our major focus of this review is to highlight the importance of SEDDSs in oral BA enhancement of poorly water-soluble drugs.

The main aim of the current research is to achieve active targeting of antimicrobials in secondary urinary tract infections using the direction of renal blood flow. The objective is further extended to maintain a constant internal environment and to deliver an extended maintenance dose using Poly lactic acid (PLLA) electrospun nanofibers. The medicated nanofibers used to evaluate their physical characteristics and drug release behaviour. Therapeutic efficacy of the developed formulation was achieved by organ distribution, pharmacokinetic and challenge study. A major fraction of drug was recovered from the kidney after 32 hours results in a significant reduction in colony forming unit (CFU) count establish the therapeutic efficacy of developed formulation. Polyanionic nature of PLLA electrospun nanofibers assists as an excellent carrier for intravaginal delivery of antimicrobial in urinary tract infections.

Background: Mycobacterium tuberculosis (M. TB) remains the prime cause of bacterial mortality and morbidity world-wide. Therefore, effective delivery and targeting of drug to the cellular tropics is essentially required to generate significant results for tuberculosis treatment. The aim of the present study was to develop and characterize ligand anchored pH sensitive liposomes (TPSL) as dry powder inhaler for the targeted delivery of drugs in the target site i.e. lungs., Method: Ligand anchored PSL (TPSL) was prepared by thin film hydration for the combined delivery of Isoniazid (INH) and Ciprofloxacin HCl (CIP HCl) using 4-aminophenyl-α-D mannopyranoside (Man) as surface functionalized ligand and characterized using different parameters., Results: It was observed that size of the ligand anchored liposomes (TPSL) was slightly more than the non-ligand anchored liposomes (PSL). Drug release was studied at different pH for 24 hrs and it was observed that liposomes exhibited slow release at alkaline pH (58-64%) as compared to macrophage pH (81-87%) where it increased dramatically due to the destabilization of pH sensitive liposome (PSL). In vitro cellular uptake study showed that much higher concentration was achieved in the alveolar macrophage using ligand anchored liposomes as compared to its counterpart. In vivo study showed that maximum drug accumulation was achieved in the lung by delivering drug using ligand anchored PSL as compared to conventional PSL., Conclusion: It was concluded that ligand anchored pH sensitive liposome is one of the promising systems for the targeted drug therapy in pulmonary tuberculosis.

Today, ∼74% of drugs are taken orally and are not found to be as effective as desired. To improve such characteristics, transdermal drug delivery was brought to existence. This delivery system is capable of transporting the drug or macromolecules painlessly through skin into the blood circulation at fixed rate. Topical administration of therapeutic agents offers many advantages over conventional oral and invasive techniques of drug delivery. Several important advantages of transdermal drug delivery are prevention from hepatic first pass metabolism, enhancement of therapeutic efficiency and maintenance of steady plasma level of the drug. Human skin surface, as a site of drug application for both local and systemic effects, is the most eligible candidate available. New controlled transdermal drug delivery systems (TDDS) technologies (electrically-based, structure-based and velocity-based) have been developed and commercialized for the transdermal delivery of troublesome drugs. This review article covers most of the new active transport technologies involved in enhancing the transdermal permeation via effective drug delivery system.

Among all cancers, lung cancer is the major cause of deaths. Lung cancer can be categorized into two classes for prognostic and treatment purposes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Both categories of cancer are resistant to certain drugs. Various mechanisms behind drug resistance are over-expression of superficial membrane proteins [glycoprotein (P-gp)], lung resistance-associated proteins, aberration of the intracellular enzyme system, enhancement of the cell repair system and deregulation of cell apoptosis. Structure-performance relationships and chemical compatibility are consequently major fundamentals in surfactant-based formulations, with the intention that a great deal investigation is committed to this region. With the purpose to understand the potential of P-gp in transportation of anti-tumor drugs to cancer cells with much effectiveness and specificity, several surfactant-based delivery systems have been developed which may include microspheres, nanosized drug carriers (nanoparticles, nanoemulsions, stealth liposomes, nanogels, polymer-drug conjugates), novel powders, hydrogels and mixed micellar systems intended for systemic and/or localized delivery.

Vaginal candidiasis or vulvovaginal candidiasis (VC) is a common mucosal infection of vagina, mainly caused by Candida species. The major symptoms of VC are dyspareunia, pruritis, itching, soreness, vagina as well as vulvar erythema and edema. Most common risk factors that lead to the imbalance in the vaginal micro biota are the use of antibiotics, pregnancy, diabetes mellitus, immuno suppression as in AIDS or HIV patients, frequent sexual intercourse, spermicide and intra-uterine devices and vaginal douching. Various anti-fungal drugs are available for effective treatment of VC. Different conventional vaginal formulations (creams, gels, suppositories, powder, ointment, etc.) for VC are available today but have limited efficacy because of lesser residence time on vaginal epithelium due to self-cleansing action of vagina. So to overcome this problem, an extended and intimate contact with vaginal mucosa is desired; which can be accomplished by utilizing mucoadhesive polymers. Mucoadhesive polymers have an excellent binding capacity to mucosal tissues for considerable period of time. This unique property of these polymers significantly enhances retention time of different formulations on mucosal tissues. Currently, various novel formulations such as liposomes, nano- and microparticles, micro-emulsions, bio-adhesive gel and tablets are used to control and treat VC. In this review, we focused on current status of vaginal candidiasis, conventional and nanotechnology inspired formulation approaches.

Tuberculosis (TB) is one of the major devastating diseases in the world, mainly caused by Mycobacterium tuberculosis. Furthermore, multi-drug resistant TB and extremely drug resistant TB are becoming big problems globally. Bacillus Calmette-Guerin (BCG) is the only available vaccine which provides protection against TB. The BCG vaccine is effective in children but not recommended in adults and elderly patients due to an associated low risk of infection with Mycobacterium tuberculosis and variable effectiveness of the vaccine. The main aim of this research study is to develop such a vaccine which will provide a better and safer profile in children and adults, as well as in elderly patients. In this present study, we prepared pulmonary tubercular vaccine by using an Antigen 85 complex (Ag85)-loaded nanocarrier such as the immunostimulating complex (ISCOM). Immunological outcomes clearly indicated significant improvement in humoral as well as cellular immune responses after pulmonary immunization with ISCOMs containing Quil A in mice.

Cardiovascular disease is the disease that affects the cardiovascular system, vascular diseases of the brain and kidney, and peripheral arterial disease. Despite of all advances in pharmacological and clinical treatment, heart failure is a leading cause of morbidness and mortality worldwide. Many new therapeutic advance strategies, including cell transplantation, gene delivery or therapy, and cytokines or other small molecules, have been research to treat heart failure. The main aim of this review article is to focus on nano carriers advancement and addressing the problems associated with old and modern therapeutics such as nonspecific effects and poor stability.

Tuberculosis, MTB or tubercle bacillus (TB) is a lethal, infectious disease mainly caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. In this study, guar gum-based porous nanoaggregates were formulated by precipitation technique with two frontline antitubercular drugs, i.e. isoniazid and rifampicin. The formulations were optimized on the basis of various evaluation parameters such as morphology, density, entrapment efficiency and in vitro drug release. The optimized formulations were administered by inhalable route to Wistar rats for the evaluation of drugs in different organs (lungs, liver and kidneys). High drug encapsulation efficiency was achieved in guar gum porous nanoaggregates, ranging from 50% to 60%. A single pulmonary dose resulted in therapeutic drug concentrations of 30%-50% in the lungs and in other organs (less than 5%) for 24 h. From this study, we can conclude that delivering drugs through pulmonary route is advantageous for local action in lungs. Furthermore, the formulation showed sustained drug release pattern, which could be beneficial for reducing the drug dose or frequency of dosing, thus helpful in improving patient compliance.

Permeability plays an important role to achieve the desired therapeutic outcomes. Present study was designed to investigate the permeability of ciprofloxacin from ultrathin polyvinyl alcohol nanofiber through different biological membranes. Results of the permeability studies indicated that nanofibers exhibit higher drug permeability than plane drug. Intestinal tissue shows maximum permeability followed by eye, trachea, sublingual, rectal, and skin. Permeability studies also inferred a steady-state release of drug of the nanofiber, whereas a high degree of fluctuations was observed in plane drug. Nanofiber being 2D nanoscale material provides numerous advantages to be used as an encapsulated carrier system to improve the therapeutic effectiveness.

Presently polymer nanofibers have received much attention due to their unique properties such as large surface area, high porosity, small pore size, superior mechanical properties and ease of addition of surface functionalities compared with any other material. Nanofibers particularly polymeric nanofiber prepared by electrospinning process can be used as carriers for the controlled drug delivery of bioactive molecules such as cytokines, growth factors, anticancer drugs, enzymes and certain vitamins. This article presents an overview of nanofibers, various techniques involved in fabrication of nanofibers, their characterization, parameters affecting electrospinning process and their applications.

Benzoyl peroxide (BPO) is generally considered as first line treatment against acne. Low water solubility and formation of larger clusters and limited skin permeation upon topical application necessitates the application of high amount of drug for desired action which leads to induction of skin irritation. In the present study, we developed BPO-loaded niosomal formulation to improve its permeation through skin. The niosomes were further loaded in the carbopol gel to improve contact time. The results of the skin permeation study, skin retention study revealed that niosomes can effectively improve the drug permeation through skin. Application of niosomal gel significantly reduced the bacterial load after a treatment of four days. This reduction in bacterial load was further resulted in a significant reduction in the inflammation with minimal skin irritation compared with plain drug and the plain niosomal formulation.

Brain tumor is one of the most challenging diseases to treat. The major obstacle in the specific drug delivery to brain is blood-brain barrier (BBB). Mostly available anti-cancer drugs are large hydrophobic molecules which have limited permeability via BBB. Therefore, it is clear that the protective barriers confining the passage of the foreign particles into the brain are the main impediment for the brain drug delivery. Hence, the major challenge in drug development and delivery for the neurological diseases is to design non-invasive nanocarrier systems that can assist controlled and targeted drug delivery to the specific regions of the brain. In this review article, our major focus to treat brain tumor by study numerous strategies includes intracerebral implants, BBB disruption, intraventricular infusion, convection-enhanced delivery, intra-arterial drug delivery, intrathecal drug delivery, injection, catheters, pumps, microdialysis, RNA interference, antisense therapy, gene therapy, monoclonal/cationic antibodies conjugate, endogenous transporters, lipophilic analogues, prodrugs, efflux transporters, direct conjugation of antitumor drugs, direct targeting of liposomes, nanoparticles, solid-lipid nanoparticles, polymeric micelles, dendrimers and albumin-based drug carriers.

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

The foremost objective of the present research study was to develop and evaluate the potential of rifampicin (RIF) and isoniazid (INH) loaded spray dried nanoembedded microparticles against experimental tuberculosis (TB). In this study, RIF-INH loaded various formulations (chitosan, guar gum, mannan, and guar gum coated chitosan) were prepared by spray drying and characterized on the basis of in vitro as well as in vivo studies. Results showed that guar gum spray dried particles showed uniform size distribution with smooth surface as compare to mannan formulations. Guar gum batches exhibited excellent flow ability attributed to their optimum moisture content and uniform size distribution. The drug release showed the biphasic pattern of release, i.e., initial burst followed by a sustained release pattern. The preferential uptake of guar gum coated formulations suggested the presence and selective uptake capability of mannose moiety to the specific cell surface of macrophages. In vivo lung distribution study showed that guar gum coated chitosan (GCNP) batches demonstrated prolonged residence at the target site and thereby improve the therapeutic utility of drug with a significant reduction in systemic toxicity. Optimized drug loaded GCNP formulation has resulted in almost 5-fold reduction of the number of bacilli as compared to control group. Histopathology study also demonstrated that none of the treated groups show any evidence of lung tissue abnormality. Hence, GCNPs could be a promising carrier for selective delivery of antitubercular drugs to alveolar macrophages with the interception of minimal side effects, for efficient management of TB.

Anomalous pancreatic ductal system has always enthralled the anatomists, surgeons, gastroenterologists and radiologists alike. With the growing use of MRCP, ERCP and endoscopic and surgical procedures, the knowledge of anatomical aberrations of pancreaticobiliary tract becomes extremely important. Moreover, the anomalous pancreatic duct morphology may be responsible for atypical gastrointestinal complains. We report an exceptionally rare case of two accessory ventral pancreatic ducts opening separately into the common bile duct proximal to the hepato pancreatic ampulla. Concomitant occurrence of an ectopic major duodenal papilla, 3.8 cm distal to the pyloric end of stomach was also seen. Moreover, the accessory pancreatic duct and the minor duodenal papilla were absent. Clinical implications and embryological description of these rare anomalies are discussed. Awareness of such rare morphological variants can go a long way in assisting effective patient management.

In the present study, nanostructured lipid carriers (NLCs) with three different lipid combinations (solid lipid:liquid lipid) were prepared through emulsification and ultrasonication using a Box-Behnken design. From the design, the best lipid combination was glyceryl monostearate and oleic acid, which gives particle of smaller size (223.73 ± 43.39nm) with high drug entrapment efficiency (78.65 ± 2.2%). In vitro release studies show that 84.60 ± 5.66% of drug was released in 24h. In vivo studies revealed that drug absorption occurs through lymphatic pathway as only 5.008 ± 0.011μg/ml of peak plasma concentration was achieved in blood plasma in presence of chylomicron inhibitor. The peak plasma concentration (Cmax) for silymarin loaded NLC was found to be 25.565 ± 0.969μg/ml as compared to silymarin suspension whose Cmax was found to be 14.050 ± 0.552 μg/ml, this confirms 2-fold increase in relative bioavailability. In vivo studies revealed that 19.268 ± 1.29μg of drug reaches to liver in 2h whereas negligible drug concentration reported in other organs. It was concluded that drug loaded NLCs was beneficial for targeting liver or other lymphatic disorders through lymphatic transport pathway. Finally, the main purpose of modifying lymphatic transport system was successfully achieved through NLCs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The main aim of this study was to develop an effective carrier system containing Ag85A-loaded guar gum nanoparticles for oral vaccination against tuberculosis. Nanoparticles were prepared by Nanoprecipitation method. The developed particles with mean diameter 895.5 ± 14.73 nm and high antigen entrapment seem to be optimum for oral vaccine delivery. The acid protection assay, Peyer's patch uptake study and in-vitro antigen study confirmed that the developed formulations can protect the antigen from harsh gastric environment and can safely deliver the antigen to the intestinal region. In vivo studies data indicated that the developed nanocarriers can induce a strong mucosal as well as systemic immune response. Therefore, the experimental evidence suggests that guar-gum nanoparticle findings indicated that the guar gum nanoparticles can be utilized for safe and effective vaccine delivery via oral route.

Problem: To determine the role of inactivated GSK3β with respect to Wnt/β-catenin pathway activation in HPV-16/18-associated cervical cancer., Method of Study: The expression of active (pGSK3β-Try(216)), inactive (pGSK3β-Ser(9)), and c-Myc as well as HPV-16/18 infection was analyzed in cervical intra-epithelial neoplasia (CIN), squamous cell carcinoma (SCCs) and normal by immunohistochemistry and multiplex PCR. The proteins level was also compared with β-catenin and APC expression., Results: The dramatic decrease of pGSK3β-Try(216) expression but ectopic overexpression of pGSK3β-Ser(9) and c-Myc was observed both in CIN and SCCs samples compared to normal tissues. 57/67 CIN and 132/153 SCCs showed HPV-16 infection, while 3/67 CIN and 4/153 SCCs were harbored with HPV-18 infection. Both the proteins were significantly upregulated in HPV-16 infected cases (P = 0.0001; P = 0.001) and also positively correlated with nuclear β-catenin (P = 0.0001; P = 0.0001)., Conclusion: The process of generation of HPV-16-associated cervical tumorigenesis is synergized with GSK3β inactivation and overactivation of Wnt/β-catenin pathway., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Migraine is a chronic disorder characterized by significant headache and various associated symptoms which worsen with exertion. Zolmitriptan approved for use in the acute treatment of migraine and related vascular headaches but are limited by high pain recurrence due to rapid drug elimination. Combinationalformulationof triptans and a nonsteroidal anti-inflammatory drug may provide a quicker and longer duration of relief from the subsequent pain during the attack. In this study, we formulate a Zolmitriptan (ZT) & ketorolac tromethamine (KT) loaded thermo reversible in-situ mucoadhesive intranasal gel (TMISG) formulation which gels at the nasal mucosal temperature and contains a bioadhesive polymer (Xyloglucan) that lengthens the residence time will enhance the bioavailability of the combinational drugs. This study uses Box-Behnken design for the first time to develop, optimize the TMISG and assess factors affecting the critical quality attributes. Histopathological study of the nasal mucosa suggested that the formulation was safe for nasal administration. The statistical difference in absolute bioavailability between oral and intranasal route suggested that intranasal route had almost 21% increases in bioavailability for ZT and for KT there was 16% increase over oral formulations. Optimized formulation would help mitigate migraine associated symptoms much better over the currently available formulations., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Nanofiber scaffold formulations (diameter less than 1000 nm) were successfully used to deliver the drug/cell/gene into the body organs through different routes for an effective treatment of various diseases. Various fabrication methods like drawing, template synthesis, fiber-mesh, phase separation, fiber-bonding, self-assembly, melt-blown, and electrospinning are successfully used for fabrication of nanofibers. These formulations are widely used in various fields such as tissue engineering, drug delivery, cosmetics, as filter media, protective clothing, wound dressing, homeostatic, sensor devices, etc. The present review gives a detailed account on the need of the nanofiber scaffold formulation development along with the biomaterials and techniques implemented for fabrication of the same against innumerable diseases. At present, there is a huge extent of research being performed worldwide on all aspects of biomolecules delivery. The unique characteristics of nanofibers such as higher loading efficiency, superior mechanical performance (stiffness and tensile strength), controlled release behavior, and excellent stability helps in the delivery of plasmid DNA, large protein drugs, genetic materials, and autologous stem-cell to the target site in the future.