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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. Thein vitrosolubility 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. [ABSTRACT FROM AUTHOR]

BACKGROUND: In resource-poor countries, there remains an alarming treatment gap for people with schizophrenia, particularly those living in rural areas. Decentralization of mental health services, including community-based outreach programmes, represents one obvious strategy for bringing appropriate care to these communities. This study set out to assess the costs and effects of such a programme in rural Karnataka in India. METHOD: Eight rural communities were visited by an outreach team, who identified cases of drug-naive or currently untreated schizophrenia. Recruited cases were provided with appropriate psychotropic medication and psychosocial support, and after obtaining informed consent were assessed every 3 months over one and a half years on symptomatology, disability, family burden, resource use and costs. A repeated-measures analysis was carried out to test for significant change in these outcome measures over this period. RESULTS: A total of 100 cases of untreated schizophrenia were recruited, of whom 28% had never received antipsychotic medication and the remaining 72% had not been on medication for the past 6 months. Summary scores for psychotic symptoms, disability and family burden were all reduced significantly, with particular improvement observed at the first follow-up assessment. Increases in treatment and community outreach costs over the follow-up period were accompanied by reductions in the costs of informal-care sector visits and family care-giving time. CONCLUSIONS: Efforts to organize community-based care such as outreach services for people with schizophrenia living in more remote areas of resource-constrained countries can bring substantial benefits to patients and families alike. [ABSTRACT FROM AUTHOR]

BACKGROUND: A widely promoted model of mental health care and prevention appropriate to many low-income countries is one that is integrated into the local primary health care system. AIMS: To examine the influence of health-seeking behaviours (demand-side factors) and the access to/availability of services (supply-side factors) on local service utilisation patterns for people with common mental disorders. METHOD: Two rural catchment populations outside Bangalore (India) and Rawalpindi (Pakistan), one with the standard primary health care system, the other with additional mental health care training and support, were screened for common mental disorders. Diagnosed cases were interviewed about their use of and perceptions of local health care services (repeated three months later). RESULTS: Individuals' use of integrated mental health and other care was modest. Principal (self-rated) supply-side factors were the cost of care, distance from treatment centre, a perception that care would not be effective, and concerns regarding stigma. Perceptions improved over three months, accompanied by an increased preference for public over private providers, but this was not restricted to the integrated care localities. CONCLUSION: The use (and therefore effectiveness) of mental health services integrated into primary care is influenced by the health-seeking behaviours and perceptions of the local population. Efforts to integrate mental health into primary care need to be accompanied by educational activities in order to increase awareness, reduce stigma and draw attention to the availability of effective treatment. [ABSTRACT FROM AUTHOR]

Objective: Develop a multi-functional imaging system that combines 1.7μm optical coherence tomography/angiography (OCT/OCTA) to accurately interrogate Hereditary Hemorrhagic Telangiectasia (HHT) skin lesions., Methods: The study involved imaging HHT skin lesions on five subjects including lips, hands, and chest. We assessed the attributes of both HHT lesions and the healthy vasculature around them in these individuals, employing quantifiable measures such as vascular density and diameter. Additionally, we performed scans on an HHT patient who had undergone anti-angiogenic therapy, allowing us to observe changes in vasculature before and after treatment., Results: The results from this pilot study demonstrate the feasibility of evaluating the HHT lesion using this novel methodology and suggest the potential of OCTA to noninvasively track HHT lesions over time. The average percentage change in density between HHT patients' lesions and control was 37%. The percentage increase in vessel diameter between lesion and control vessels in HHT patients was 23.21%., Conclusion: In this study, we demonstrated that OCTA, as a functional extension of OCT, can non-invasively scan HHT lesions in vivo. We scanned five subjects with HHT lesions in various areas (lip, ear, finger, and palm) and quantified vascular density and diameter in both the lesions and adjacent healthy tissue. This non-invasive method will permit a more comprehensive examination of HHT lesions., Significance: This method of non-invasive imaging could offer new insights into the physiology, management, and therapeutics of HHT-associated lesion development and bleeding.

Optical coherence tomography (OCT) is a non-invasive diagnostic method that offers real-time visualization of the layered architecture of the skin in vivo. The 1.7-micron OCT system has been applied in cardiology, gynecology and dermatology, demonstrating an improved penetration depth in contrast to conventional 1.3-micron OCT. To further extend the capability, we developed a 1.7-micron OCT/OCT angiography (OCTA) system that allows for visualization of both morphology and microvasculature in the deeper layers of the skin. Using this imaging system, we imaged human skin with different benign lesions and described the corresponding features of both structure and vasculature. The significantly improved imaging depth and additional functional information suggest that the 1.7-micron OCTA system has great potential to advance both dermatological clinical and research settings for characterization of benign and cancerous skin lesions.

We present a comprehensive inventory of amphibians from Panna Tiger Reserve in Madhya Pradesh based on morphological, molecular and bioacoustic data. Representatives of 15 anuran species were collected, corresponding to roughly four fifths of the known amphibian species of Madhya Pradesh. The main results of this study are: (1) Description of advertisement calls of eleven species, including the first-time description of advertisement calls of Sphaerotheca pashchima. (2) Identification of cryptic species using acoustic and molecular techniques. (3) Five new significant range extensions and new state records. (4) Description of geographical variation in call properties in three anuran species. This study also provides morphological descriptions with ecological and natural history notes for each species that may be useful in management planning for amphibian conservation in Panna Tiger Reserve.

Competing Interests: None

Epidemiology is a vital tool of public health. The usefulness of epidemiology is not only about numbers of persons' ill in the community but also to understand the associations, the presentation, identification of new syndromes, to map the historical trends, and calculate morbid risk. The emotional impact of the diagnosis of cancer is well-recognized. Indian cancer research relating to the psychosocial aspects has been largely limited to counting the numbers with psychiatric syndromes. The review covers 12 years of the Indian research in psycho-oncology to understand the different aspects of epidemiology. During the review period, there are growing number of epidemiological studies (29); psychiatric morbidity ranges from 41.7% to 46%; and prevalence rate ranges from 4.4% to 97.8% for anxiety and 1.2%-89.9% for depression; majority of the studies have used one-stage screening for assessment, which is not the ideal method of identifying mental disorders. The severity of the disorders is presented only in nine studies. Quality of life is the most common associated dimension of the studies. There is the absence of studies of posttraumatic growth, resilience, and spirituality. This review calls for greater rigor in the planning of studies of emotional impact, especially the use of two-stage method, longitudinal studies, studies of different types of cancer and in different stages, include additional measures such as disease burden, coping, resilience, spirituality, and the family/social factors to understand the emotional aspects of living with cancer. There is a need for describing the emotional aspects of living with cancer (lived-in experiences) beyond the clinical syndromes., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Palliative Care.)

Purpose of Review: Psycho-oncology has completed 25 years. There is growing recognition of the psychosocial needs of persons living with cancer and the role of sociocultural factors in addressing the needs. This review addresses the research in developing countries relating to distress associated with living with cancer and psychosocial care., Recent Findings: There is growing recognition of the emotional needs, understanding of the sociocultural aspects of the emotional responses of persons, caregivers, role of resilience and posttraumatic growth and spirituality in cancer care. Psychosocial aspects of cancer are largely influenced by social, economic, cultural, religious and health systems. A number of innovative approaches to care like use of yoga, financial and material support and involvement of caregivers have been implemented. A positive development is the increasing professional attention to document and develop innovative care programmes., Summary: A significant proportion of the general population are living with cancer. There are significant psychosocial needs largely influenced by social, economic, cultural, religious aspects of the communities. There are a wide range of interventions from self-care to professional care to address the needs. In developing countries, there is need for longitudinal studies of psycho-social experiences, develop interventions that are culturally appropriate, along with enhanced use of information technology along with evaluation of interventions.

Purpose: To prepare 7-epidocetaxel (7ED) and 10-oxo-7-epidocetaxel (10-O-7ED) formulations as like marketed Taxotere® (TXT) injection and to screen them for in vitro and in vivo anticancer efficacy including their in vivo toxicity behavior., Methods: The 7ED and 10-O-7ED formulations were screened for in vitro anti-proliferative, anti-metastatic and cell cycle arresting behaviors. Further, in vivo acute toxicity of TXT injection containing 10% of 7ED and 10-O-7ED separately and the therapeutic study of 10-O-7ED alone were studied in B16F10 experimental metastasis mouse model., Results: 10-O-7ED caused significantly higher cytotoxicity after 48 and 72 h than 22 h study. 10-O-7ED showed significantly increased in vitro anti-metastatic activity than TXT. The TXT caused more arrest of cells at S phase, whereas 10-O-7ED arrested more at G2-M phase and vice versa at higher concentration. In vivo acute toxicity study revealed better therapeutic effect with reduced toxicity of TXT containing 10% 10-O-7ED than TXT alone. Similarly, the therapeutic study revealed significantly less number of surface metastatic nodules formation with 10-O-7ED treated group (107 ± 49) (***p < .0001) than control group (348 ± 56). Also, the control group showed significant weight loss at the end (20th day) of the experiment (*p < .05, p = .041) than 10-O-7ED treated group which showed about 4% increased mean group weight., Conclusion: Our study revealed the significantly higher in vivo anti-metastatic behavior, with no toxicity, of 10-O-7ED. However, it is a preliminary observation being noticed but further investigations are needed to address the potential of 10-O-7ED in cancer treatment with mechanisms behind the improved therapeutic efficacy with no toxicity.

Acylated chitosan (Myristoyl and Octanoyl) coated paclitaxel-loaded liposomal formulation was developed with an aim to overcome the cremophor EL related toxicities. They were evaluated for drug entrapment, in vitro drug release, and cytotoxicity and cell uptake behavior using A549 cells. The 99m Tc radio-labeled formulations were also evaluated in vivo in Ehrlich Ascites Tumor (EAT) bearing mice for biodistribution and tumor uptake. The mean particle size of both coated and uncoated liposomal formulations was found to be in the range of 180-200 nm with high drug entrapment efficiency (>90% in case of uncoated liposomes and 80 ± 5% in case of coated liposomes). The uncoated liposomes displayed negative zeta potential (-10.5 ± 4.9 mV) whereas coated liposomes displayed positive zeta potential in the range of +21 to +27 mV. Slower drug release was observed in case of liposomes coated with acylated chitosans as compared to uncoated and native chitosan coated liposomes. All liposomal formulations were found less cytotoxic than paclitaxel injection (Celtax™, Celon Labs, India). In vitro cell uptake and intracellular distribution studies confirmed the cytosolic delivery of uncoated and coated liposomes. The myristoyl chitosan coated liposomal system (LMC) exhibited improved pharmacokinetic, biodistribution and tumor uptake characteristics over other formulations. These obtained results confirmed the potential application of acylated chitosn coated liposomal delivery systems (LMC) in tumor targeting of paclitaxel and other drugs., (Copyright © 2018 Elsevier B.V. All rights reserved.)

More than 35 million people are living with HIV worldwide with approximately 2.3 million new infections per year. Cascade of events (cell entry, virus replication, assembly and release of newly formed virions) is involved in the HIV-1 transmission process. Every single step offers a potential therapeutic strategy to halt this progression and HIV fusion into the human host cell is one such stage. Controlling the initial event of HIV-1 transmission is the best way to control its dissemination especially when prophylaxis is concerned. Action is required either on the HIV's or host's cell surface which is logically more rational when compared with other intracellular acting moieties. Aim of this manuscript is to detail the significance and current strategies to halt this initial step, thus blocking the entry of HIV-1 for further infection. Both HIV-1 and the possible host cell's receptors/co-receptors are under focus while specifying the targets available for inhibiting this fusion. Current and under investigation moieties are categorized based on their versatile mechanisms. Advanced drug delivery and nanotechnology approaches present a key tool to exploit the therapeutic potential in a boosted way. Current drug delivery and the impact of nanotechnology in potentiating this strategy are detailed.

Currently, one-third of the world's population is infected with tuberculosis (TB) mainly spread by inhalation of the tubercle bacilli, Mycobacterium tuberculosis. Patient non-compliance is the major reason for failure of anti-tubercular drugs (ATDs) chemotherapy due to multidrug administration for longer duration of time period. The main aim of current research study was to develop and characterize inhalable spray-dried particles for pulmonary delivery of ATDs, i.e., rifampicin (RIF) and isoniazid (INH). ATDs-loaded alginate particles were prepared by ionotropic gelation technique followed by spray drying and characterized on the basis of various evaluation parameters. Results showed that the optimized spray-dried particles were found to be spherical in shape with excellent flow properties. The drug release showed the biphasic pattern of release, i.e., initial burst (30-40% up to 4 h) followed by a sustained release pattern (90% up to 60 h). Optimized formulations exhibited lower cytotoxicity and excellent lung uptake up to 8 h. Optimized formulation also showed higher rate and extent of drug uptake by lungs due to preferential phagocytosis be macrophage. In future, alginate particles could be a promising carrier for targeted delivery of ATDs to alveolar macrophages for efficient management of TB.

Purpose of Review: Understand recent developments in psychosocial and behavioral aspects of populations affected by humanitarian emergencies. The review covers the prevalence, longitudinal course, risk factors, posttraumatic growth, biological basis and interventions to address the needs., Recent Findings: Populations living in humanitarian emergencies, over 50 million worldwide, have higher risk of developing a range of mental disorders. There is evidence of persistence of these disturbances over long periods of time. There is growing body of knowledge to indicate the biological pathways to the occurrence of mental disorders. A proportion of population report posttraumatic growth. There is new focus on identifying the characteristics of risk factors, resilience at the individual, family, community and societal levels. Range of interventions to address the mental health needs is in use from strengthening the coping of individuals, parenting, school-based interventions and use of cognitive behavior therapy. Biological basis is becoming clear., Summary: The most important message of the review is the high mental health needs of individuals living in emergency situations and the urgent need to work toward adequate preparedness for natural disasters, integrate psychosocial interventions as part of relief, rehabilitation and reconstruction and work toward preventing situations of conflict, war, migration and refugee situations.

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.

In this article, a portable microfluidic microscopy based approach for automated cytological investigations is presented. Inexpensive optical and electronic components have been used to construct a simple microfluidic microscopy system. In contrast to the conventional slide-based methods, the presented method employs microfluidics to enable automated sample handling and image acquisition. The approach involves the use of simple in-suspension staining and automated image acquisition to enable quantitative cytological analysis of samples. The applicability of the presented approach to research in cellular biology is shown by performing an automated cell viability assessment on a given population of yeast cells. Further, the relevance of the presented approach to clinical diagnosis and prognosis has been demonstrated by performing detection and differential assessment of malaria infection in a given sample., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Psycho-oncology is a well-established field in the developed countries and 'distress' is recognised as the sixth vital sign in the care of persons diagnosed with cancer. However, centres in India caring for cancer do not make psycho-social aspects an essential part of their care programmes. The present narrative presents the personal journey of the author, reviews the situation of psycho-oncology in India and presents a three-part agenda for action., Competing Interests: Conflicts of Interest: None declared.

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.

Context: Artemether and lumefantrine combination therapy is well-accepted for uncomplicated malaria treatment. However, the current available formulation has several pharmacokinetic mismatches such as drug degradation in gastrointestinal tract, erratic absorption, etc. Hence, need of the hour is the injectable formulation, which can overcome the pharmacokinetic mismatch associated with current available formulation in the market., Objective: To fabricate artemether and lumefantrine co-loaded injectable nanostructured lipid carriers (NLCs) formulation., Materials and Methods: Artemether and lumefantrine co-loaded NLCs were fabricated using homogenization followed by ultra-sonication method. Fabricated NLCs were evalauated for their physicochemical characteristics, and suitability of the formulation for malaria treatment was evaluated using in vivo animal model (Plasmodium berghei-infected mice). Results, discussion and conclusion: Artemether and lumefantrine co-loaded NLCs had a hydrodynamic diameter of ∼ 145 nm with the surface charge of -66 mV. Due to the lipophilic nature of both antimalarial drugs, both single drugs-loaded and co-loaded NLCs have shown high encapsulation efficiency, which is 84% for artemether and 79% for lumefantrine. In vitro drug release study has shown a biphasic drug release pattern, which has shown 63% artemether release and 45% of lumefantrine release over a time period of 30 h. Plasmodium berghei-infected mice treated with artemether and lumefantrine co-loaded NLCs showed better antimalarial activity with respect to parasitemia progression and survivability period.

Mucoadhesive tablets have emerged as potential candidates for gastroretentive drug delivery providing controlled release along with prolonged gastric residence time. Gastroretentive mucoadhesive tablets could result in increased bioavailability due to prolonged gastric residence time. A hydrophilic matrix system was developed as mucoadhesion is achievable on appropriate wetting and swelling of the polymers used. The polymers were so chosen so as to provide a balance between swelling, mucoadhesion and drug release. The polymers chosen were hydroxypropyl methylcellulose K4M, chitosan, and Carbopol 934. The concentrations of these polymers used has a great impact on the physicochemical properties of the resulting formulation. The tablets were formulated using wet granulation method and tranexamic acid was used as the model drug. The prepared tablets were characterized for size, shape, appearance, hardness, friability, weight variation, swelling, mucoadhesion and in vitro drug release. Several batches of tablets were prepared by varying the ratio of hydroxypropyl methylcellulose K4M and Chitosan. The batches having a greater ratio of chitosan showed higher rate of swelling, greater erosion, less mucoadhesion and faster release rate of the drug whereas the batches having greater ratio of hydroxypropyl methylcellulose K4M showed lesser rate of swelling, less erosion, better mucoadhesion and a smaller drug release rate. The level of carbopol was kept constant in all the batches.

A novel, reversed-phase high-performance liquid chromatographic method was developed and validated for the determination of related substances in Plerixafor (PLX) drug substance. PLX is an immunostimulant used to mobilize hematopoietic stem cells in cancer patients. The method is efficient for estimation of all degradation and process-related impurities. The method was developed using the Phenomenex Luna L11 column using the gradient program with mobile phase A and mobile phase B, where mobile phase A consists of pH 2.0 1-heptanesulfonic acid sodium salt buffer and acetonitrile in the ratio of 80:20 (v/v) and mobile phase B consists of pH 2.0 1-heptanesulfonic acid sodium salt buffer and acetonitrile in the ratio of 20:80 (v/v). PLX and its impurities were monitored at 210 nm. The present work is describing the role of ion-pair reagent in the separation of polar compounds. PLX was subjected to various stress conditions of oxidative, acid, base, hydrolytic, thermal, humidity and photolytic degradations. The degradation products were well separated from each other and with the main peak, demonstrating the stability-indicating power of the method. The performance of the method was validated according to the present ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Purpose: The synthesis and evaluation of novel biodegradable poly(organophosphazenes) (3-6) namely poly[bis-(2-propoxy)]phosphazene (3) poly[bis(4-acetamidophenoxy)]phosphazene (4)poly[bis(4-formylphenoxy)]phosphazene (5) poly[bis(4-ethoxycarbonylanilino)]phosphazene (6) bearing various hydrophilic and hydrophobic side groups for their application as nonocarrier system for antimalarial drug delivery is described., Methods: The characterization of polymers was carried out by IR, (1)H-NMR and (31)P-NMR. The molecular weights of these novel polyphosphazenes were determined using size exclusion chromatography with a Waters 515 HPLC Pump and a Waters 2414 refractive index detector. The degradation behavior was studied by 200 mg pellets of polymers in phosphate buffers pH 5.5, 6.8 and 7.4 at 37°C. The degradation process was monitored by changes of mass as function of time and surface morphology of polymer pellets. The developed combined drugs nanoparticles formulations were evaluated for antimalarial potential in P. berghei infected mice., Results: These polymers exhibited hydrolytic degradability, which can afford applications to a variety of drug delivery systems. On the basis of these results, the synthesized polymers were employed as nanocarriers for targeted drug delivery of primaquine and dihydroartemisinin. The promising in vitro release of both the drugs from nanoparticles formulations provided an alternative therapeutic combination therapy regimen for the treatment of drug resistant malaria. The nanoparticles formulations tested in resistant strain of P. berghei infected mice showed 100% antimalarial activity., Conclusions: The developed nanocarrier system provides an alternative combination regimen for the treatment of resistant malaria.

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.)

Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, (1)H NMR, (31)P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35days without any recrudescence, thus proving to be effective against resistant malaria. The study provides an alternative combination regimen found to be effective in the treatment of resistant malaria., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A novel stability-indicating reverse phase high performance liquid chromatography method was developed and validated for the simultaneous determination of Celecoxib (CEL) and Diacerein (DIN) and its impurities in capsule dosage form. The method was developed using L1 column with gradient using the mobile phase consist of Solution A (pH = 2.3 buffer) and Solution B (methanol and acetonitrile; 50 : 50, v/v). The eluted compounds were monitored at 255 nm. CEL and DIN were subjected to oxidative, acid, base, hydrolytic, thermal and photolytic stress conditions. The developed method was validated as per International Conference on Harmonisation guidelines with respect to specificity, linearity, limit of detection, limit of quantitation, accuracy, precision and robustness. The limit of quantitation results were ranged from 0.07 to 0.09 µg/mL for CEL impurities and 0.052 to 0.065 µg/mL for DIN impurities. This method is suitable for the estimation of impurities and assay of CEL and DIN in capsules dosage forms., (© The Author [2014]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cancer becomes the leading cause of deaths worldwide, including breast cancer, prostate cancer and lung cancer that preferentially metastasize to bone and bone marrow. Bisphosphonates (BPs) have been used successfully for many years to reduce the skeletal complications related with the benign and malignant bone diseases that are characterized by enhanced osteoclastic bone resorption. Nitrogen-containing bisphosphonates (N-BPs) have also been demonstrated to exhibit direct anti-tumour effects. BPs binds avidly to the bone matrix, and released from matrix during bone resorption process, BPs are internalized by the osteoclasts where they interfere with biochemical pathways and induce osteoclast apoptosis. BPs also antagonizes the production of osteoclast and promotes the osteoblasts proliferation. Currently, Zoledronic acid is widely used as one of the BP having high bone specificity and potential to inhibit the osteoclast-mediated bone resorption. In addition to inhibition of cell multiplication and initiation of apoptosis in cultured cancer cells, they also interfere with adhesion of cancer cells to the bone matrix and inhibit cell migration and invasion. Pathophysiology and current target therapies like conjugate of BPs with liposomes, nanoparticle used for the treatment of bone cancer is reviewed in this article along with the use of different BPs.

Lymphatic system is a key target in research field due to its distinctive makeup and huge contributing functions within the body. Intestinal lymphatic drug transport (chylomicron pathway) is intensely described in research field till date because it is considered to be the best for improving oral drug delivery by avoiding first pass metabolism. The lymphatic imaging techniques and potential therapeutic candidates are engaged for evaluating disease states and overcoming these conditions. The novel drug delivery systems such as self-microemulsifying drug delivery system, nanoparticles, liposomes, nano-lipid carriers, solid lipid carriers are employed for delivering drugs through lymphatic system via various routes such as subcutaneous route, intraperitoneal route, pulmonary route, gastric sub-mucosal injection, intrapleural and intradermal. Among these colloidal particles, lipid-based delivery system is considered to be the best for lymphatic delivery. From the last few decades, mesenteric lymph duct cannulation and thoracic lymph duct cannulation are followed to assess lymphatic uptake of drugs. Due to their limitations, chylomicrons inhibitors and in-vitro models are employed, i.e. lipolysis model and permeability model. Currently, research on this topic still continues and drainage system used to deliver the drugs against lymphatic disease as well as targeting other organs by modulating the chylomicron pathway.

Neuropilin-1, a transmembrane receptor entailed in wide range of human tumour cell lines and diverse neoplasms, mediates the effects of VEGF and Semaphorins during the processes of cellular proliferation, survival and migration. In view of this, we had developed and evaluated in vitro and in vivo efficacy of anti-neuropilin-1 immunoliposomes against neuropilin-1 receptor expressing tumours. The PEGylated liposomes loaded with docetaxel were prepared using thin film hydration method. Functionalised PEGylated liposomes were prepared using post-insertion technique. Anti-neuropilin-1 immunoliposomes were prepared by covalently conjugating Fab' fragments of neuropilin-1 antibody to functionalised PEGylated liposomes via thioether linkage. In vivo evaluation of Taxotere and liposomal formulations was performed using intradermal tumour model to demonstrate anti-angiogenic and tumour regression ability. The modified Fab' fragments and immunoliposomes were found to be immunoreactive against A549 cells. Further, docetaxel loaded PEGylated liposomes and PEGylated immunoliposomes demonstrated higher in vitro cytotoxicity than Taxotere formulation at the same drug concentration and exposure time. The live imaging showed distinctive cellular uptake of functional immunoliposomes. Further, significant decrease in micro-blood vessel density and tumour volumes was observed using bio-engineered liposomes. The results clearly highlight the need to seek neuropilin-1 as one of the prime targets in developing an anti-angiogenic therapy.