Development of Mucoadhesive Gel Microbicide to Target Mucosal HIV Reservoirs

The wide use of microbicide is mainly depends on its effectiveness, less frequent application, ready availability and most importantly cost. The aim of this work was to develop affordable microbicide mucoadhesive gel formulation of synthetic anti HIV drug, stavudine and to characterise it in terms of its physical properties, mucoadhesiveness and spreadability. The purpose of the present study was also to compare different dissolution media used for in vitro release of vaginal dosage form. The gels were tested for antimicrobial, spermicidal and anti-HIV activity. Gels prepared using Carbopols and Polycarbophil were transparent and homogenous and had excellent mucoadhesion index - and showed fast drug release profile. Gels showed very good antimicrobial action against pathological microorganism

Exploring Nanotechnologies for the Effective Therapy of Malaria using Plant-Based Medicines

Malaria is a potentially lethal disease caused by species of the plasmodium parasite. Despite the advances in the interventions for its control and approaches to manage fatality, morbidity and mortality rates associated with malaria are still high. At present, artemisinin-based combination therapy is the first line of treatment. However, there is the need to explore newer approaches as reduced effectiveness and multi-drug resistance (even to artemisinin) has been reported in some regions and is expected to widen in scope. Phytomedicines have shown promise for the management of this debilitating disease and there are abundant resources in most of the areas where this disease is endemic. This report would systematically review the literature, emphasizing the challenges encountered in the control of malaria, active phytochemicals currently utilised in the management, drug delivery approaches as well as the nanotechnology-based systems that could be exploited in its treatment. These phytomedicines, either delivered conventionally or via the use of advanced delivery systems may suggest new strategies towards the better management of malaria

A Comprehensive Review on Dry Eye Disease: Diagnosis, Medical Management, Recent Developments, and Future Challenges

Dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS) is a common disorder of the tear film caused by decreased tear production or increased evaporation and manifests with a wide variety of signs and symptoms. The present review from interpretation of the literature gives detailed information on the prevalence, definition, causes, diagnostic tests, and medical management of dry eye disease. A number of systems contribute to the physiological integrity of the ocular surface and disruption of system may or may not produce symptoms. Therefore accurate diagnosis of dry eyes with no or minimal disruption of physiological function is necessary. The paper also discusses different colloidal drug delivery systems and current challenges in the development of topical ophthalmic drug delivery systems for treatment of KCS. Due to the wide prevalence and number of factors involved, newer, more sensitive diagnostic techniques and novel therapeutic agents have been developed to provide ocular delivery systems with high therapeutic efficacy. The aim of this review is to provide awareness among the patients, health care professionals, and researchers about diagnosis and treatment of KCS and recent developments and future challenges in management of dry eye disease

Enhanced anti-psoriatic efficacy and regulation of oxidative stress of a novel topical babchi oil (Psoralea corylifolia) cyclodextrin-based nanogel in a mouse tail model

Psoriasis is a proliferative inflammatory skin disorder with relapsing episodes. Herein, the efficacy of babchi oil (BO) loaded nanostructure gel was evaluated for antipsoriatic activity and oxidative stress biomarkers assessment using mouse tail model. BO was entrapped into cyclodextrin-based nanocarriers (360.9 ± 19.55 nm), followed by incorporation into a Carbopol gel and characterized for viscosity, spreadability and texture analysis. The gels were topically applied on mouse-tails once daily for fourteen days. Evaluation of antipsoriatic activity as determined by histopahological observations of orthokeratotic epidermis revealed two times higher efficacy of BO nanogel than the native BO gel. Further, significantly enhanced superoxide dismutase (SOD) and reduced glutathione (GSH) levels and diminished malondialdehyde (MDA) and nitrite (NO) levels revealed that nanogels played a major role in management of ROS associated in psoriasis pathogenesis. Hence, this study provides strong evidence for use cyclodextrin-based nanogels as safe and better delivery carrier of BO for management of psoriasis

Albumin Based Iohexol Nanoparticles for Computed Tomography: An In Vivo Study

Iohexol is a commonly used second generation non-ionic iodinated contrast agent with a multitude of advantages such as low osmolarity and competent intravenous countenance having minimum adverse reactions. Our study anticipated to improve the efficacy of Iohexol as a contrast enhancing agent for Computed Tomography, by envisaging bio-compatible albumin based Iohexol nanoparticles. This nanoparticulate system was developed primarily to enhance the anatomic imaging while increasing its residence time in the blood pool. Towards this goal, we developed Iohexol albumin nanoparticles using glutaraldehyde as a cross linking agent, and Polyethylene glyocol Iohexol albumin nanoparticles by physical adsorption to ameliorate its circulation time. These formulations were studied in comparison to the clinically available Iopamidol™. Both Iohexol albumin nanoparticles and Polyethylene glyocol Iohexol albumin nanoparticles were characterized for its size, physicochemical properties and entrapment efficiency. Iohexol albumin nanoparticles showed a size range of 254±5 nm and post surface modification the size of Polyethylene glyocol Iohexol albumin nanoparticles was found to be 283±7 nm in diameter, with and entrapment efficiency Iohexol as of 85%. Further, In vivo computed tomography imaging in New Zealand white rabbits for the developed formulations manifested an enhancement in the anatomical structures of heart, liver and kidneys along with an increased residence time in the blood pool of 3 h in contrast to Iopamidol™. Our study interprets that Polyethylene glyocol Iohexol albumin nanoparticles have prolonged residence time producing much greater conspicuity of anatomic features and warrants further detail study of the formulation in disease models

Development and validation of high-performance liquid chromatographic method for quantification of irinotecan and its active metabolite SN-38 in colon tumor bearing NOD/SCID mice plasma samples: Application to pharmacokinetic study

Irinotecan (IRT) is an antineoplastic agent widely used in the treatment of various cancers primarily in colorectal cancer. A new, simple and sensitive high-performance liquid chromatography (HPLC) method coupled with fluorescence detector was developed and validated to quantify IRT and its active metabolite SN38 in the plasma of non-obese diabetic/severe combined immune-deficient mice (NOD/SCID) mice bearing colon tumor. The plasma samples were extracted by precipitation method using acetonitrile with 0.1% formic acid. The chromatographic separation was achieved using mobile phase consisted of water and acetonitrile (57:43 v/v) pH 3 at the flow rate of 0.8 mL/min in C18 column (internal diameter, 250 × 4.6 mm; pore size, 5 μm). The method was validated according to the bioanalytical guidelines defined by Food and Drug Administration (FDA) and European Medicine Agency (EMA). A regression (R2 ) value of 0.999 and 0.997 for IRT and SN38 suggested the good linearity in the range of 0.1–10 μg/mL and 5–500 ng/mL, respectively. The calculated lower limit of quantification (LLOQ) and limit of detection (LOD) for IRT were 0.1 and 0.065 μg/mL, respectively. However, for SN38, LLOQ and LOD were 5 and 2 ng/mL, respectively. The intra-day and inter-day variations (coefficient of variance; % CV) observed during the validation were found to be within the set limit of 15%. Both accuracy and percentage recovery analyzed and calculated from the quality control samples were in the between the defined range of 85–115%. Plasma samples were found to be stable when stored at room temperature for 2 h, after 2 freeze–thaw cycles and at −80 °C for 2 months. The developed method was successfully applied to study the plasma elimination profile of IRT in NOD/SCID mice with tumor. The results from plasma concentration time profile and pharmacokinetic parameter analyzed suggested the rapid elimination of IRT and SN38 from the plasma of NOD/SCID mice

Rational design of polysorbate 80 stabilized human serum albumin nanoparticles tailored for high drug loading and entrapment of Irinotecan

Human serum albumin (HSA) nanoparticles are considered to be versatile carrier of anticancer agents in efficiently delivering the drug to the tumor site without causing any toxicity. The aim of the study was to develop stable HSA nanoparticles (NPs) of drug irinotecan (Iro) having slightly water solubility and moderate HSA binding. A novel strategy of employing a hydrophilic non-ionic surfactant polysorbate 80 which forms protein-polysorbate 80 complex with increased affinity and improvement in Iro-HSA binding has been used to maximize the loading and entrapment efficiency of Iro in HSA-NPs. Bespoke nanoparticles with entrapment efficiency (79.09%) and drug loading of 9.62% could be achieved with spherical shape and particle size of 77.38 nm, 0.290 polydispersity index and -23.7 mv zeta potential. The drug entrapment in nanoparticles was confirmed by Differential Scanning Calorimeter, Fourier Transformation Infrared Spectroscopy and Fluorescence spectroscopy. In-vitro release of Iro from nanoparticles showed biphasic-release with initial burst followed by prolonged release upto 24h.The short-term stability investigation of nanodispersion showed no significant changes in physicochemical properties of nanoparticles. Long-term studies on freezedried Iro-HSA-NPs indicated good stability of nanoparticles up to 12 months. This is the first report for efficient fabrication of Iro delivery system based on HSA nanoparticles. [Abstract copyright: Copyright © 2017. Published by Elsevier B.V.

Formulation and development of orodispersible sustained release tablet of domperidone

Commercially available domperidone orodispersible tablets (ODT) are intended for immediate release of the drug, but none of them have been formulated for sustained action. The aim of the present research work was to develop and evaluate orodispersible sustained release tablet (ODT-SR) of domperidone, which has the convenience of ODT and benefits of controlled release product combined in one. The technology comprised of developing sustained release microspheres (MS) of domperidone, followed by direct compression of MS along with suitable excipients to yield ODT-SR which rapidly disperses within 30 seconds and yet the dispersed MS maintain their integrity to have a sustained drug release. The particle size of the MS was optimized to be less than 200 μm to avoid the grittiness in the mouth. The DSC thermograms of MS showed the absence of drug-polymer interaction within the microparticles, while SEM confirmed their spherical shape and porous nature. Angle of repose, compressibility and Hausner's ratio of the blend for compression showed good flowability and high percent compressibility. The optimized ODT-SR showed disintegration time of 21 seconds and matrix controlled drug release for 9 h. In-vivo pharmacokinetic studies in Wistar rats showed that the ODT-SR had a prolonged MRT of 11.16 h as compared 3.86 h of conventional tablet. The developed technology is easily scalable and holds potential for commercial exploitation

Chemometrics-assisted development of a validated LC method for simultaneous estimation of temozolomide and γ-linolenic acid: Greenness assessment and application to lipidic nanoparticles

The described work entails the development of a simple, sensitive, green, and robust high-performance liquid chromatographic (HPLC) method for simultaneous estimation of temozolomide (TMZ) and γ-linolenic acid (GLA). The chemometric factor screening study helped identify the critical method parameters optimized using Box-Behnken design for improved understanding and enhancing the method performance. Chromatographic separation was performed on a Kinetex® C18 column (150 × 4.6 mm, 5 µm particle size) using methanol: water (pH adjusted to 3.5 using 0.5% v/v O-phosphoric acid) as the mobile phase at 0.5 mL/min flow rate and diode array detection between 210 and 360 nm. The linearity of the method was observed for concentrations of TMZ and GLA ranging between 1 and 100 µg.mL−1 (R2 = 0.999, p < 0.05). Accuracy evaluation showed good percent recovery within 97.9–100%, while intra- and inter-day precision showed RSD values within 0.37%-1.01%. The limit of detection and quantification for TMZ was found to be 0.75 and 1.0 μg.mL−1, respectively, while the values 0.55 and 1.0 μg.mL−1, respectively, were observed for GLA. System suitability (96.9–102.8%), its limits, and robustness evaluation indicated good percent recovery within, while RSD values were found to be within the acceptable limit of less than 2%. The method was specific for its ability to detect the analytes and their degradation products during forced degradation studies, which also indicated that TMZ was highly prone to alkaline conditions while GLA showed mild degradation in all the studied conditions. The estimation of both the analytes from lipid nanoparticles formulation showed good values for total drug content (82.6–85.3%), entrapment efficiency (95.4 to 98.7%), and drug loading (25.2 to 38.4%). Overall, the results indicated that the developed method was reliable for its accuracy, precision, sensitivity, and specificity for simultaneous estimation of the analytes. The method was found to be stability-indicating in nature and suitable for simultaneous estimation of TMZ and GLA from the developed nanoparticles formulation. Further, employing a greenness assessment approach established the method greenness