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Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50∶50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.

This article introduces a novel strategy for devising an optimal Static Synchronous Compensator (STATCOM) controller via Hamiltonian function method in mitigating the transient stability of a multimachine power system. The STATCOM, a second generation shunt type FACTS device, is popularly employed for power system control. To test the applicability of the Hamiltonian function approach, an IEEE Type WSCC 9-bus system is taken under study. An appropriate Hamiltonian functional has been framed using the parameters of the test system, which is applied to optimize the preferred performance index. The performance of the proposed nonlinear controller is judged against a regular state feedback based STATCOM controller. The parameters of this traditional controller are computed via dynamical Games of the Nash Equilibrium method. The proposed method is beneficial in terms of mathematical complexity as needed in estimating relative degree and coordinate transformation in the feedback linearization method. A detailed investigation of the results reveals that the proposed controller is effective and efficient to a greater degree than the traditional STATCOM controller in a multimachine system, even at some point in serve eventualities like earth fault scenarios.

This study focuses on the development and characterization of a novel liposomal gel formulation intended for ocular drug delivery. The liposomal gel was prepared using the thin-film hydration method, with Tween-80 employed as a stabilizing agent to prevent aggregation. The encapsulation efficiency, particle size, zeta potential, and polydispersity index (PDI) of the liposomal formulation containing the active ingredient, timolol maleate, were evaluated. The encapsulation efficiency was found to be 57.47%, with a particle size of 340.8 nm and a zeta potential of -29.0 mV. The polydispersity index was determined to be 0.576, indicating a uniform distribution of liposome sizes and good stability of the formulation. The developed liposomal gel aims to enhance drug permeation, optimize therapeutic response, and minimize potential side effects associated with conventional forms of the drug. The incorporation of multilamellar vesicles into the gel matrix is expected to prolong drug residence time at the ocular surface, thereby improving drug absorption and reducing dosing frequency. Additionally, the mucoadhesive properties of the carbopol 940 gel base further enhance ocular residence time, leading to improved patient compliance and comfort. Overall, the prepared liposomal gel formulation shows promise as an effective ocular drug delivery system. Further in vitro and in vivo studies are warranted to evaluate its pharmacokinetic and pharmacodynamic profiles, as well as its safety and efficacy for clinical use.

Glaucoma affects millions worldwide. Untreated, it might cause lifelong blindness. Traditional treatments have been limited and intrusive. Liposomes are changing glaucoma treatment. Phospholipid bilayer liposomes can carry medications for targeted administration. This innovative glaucoma medication has huge potential to transform the way we treat it. This essay will explain liposomes, how they function, and why they are a glaucoma therapy game-changer. Eyes have several sensory compartments. Eyes send brain impulses. Eye-aqueous humour production causes glaucoma. It mostly affects the over-50s. Glaucoma destroys retinal ganglion cells and the optic nerve, causing blindness. CO2 inhibitors treat it. This inhibitor keeps aqueous humour from the ocular fluid. Normal eye medication dosage. This ocular drug administration approach relies on nasolacrimal drainage and tears turnover to provide the usual dose form. Low bioavailability. Novel pharmaceutical delivery dose formulations can fix this. Nano co-adhesive compositions prolong ocular drug delivery. Liposomes cure glaucoma uniquely. Bioavailability lowers toxicity and dosage. Novel Drug Delivery System helps glaucoma patients worldwide. Liposomes drop IOP slowly. Aqueous liposomes have natural and synthetic phospholipid bilayers. Liposomes contain hydrophilic medicines. Liposomes resemble cells. Their properties make them cling to cells. Biocompatible liposomes increase drug solubility, stability, absorption, and toxicity. Conjunctiva and cornea interactions with liposomes impact tear dynamics and medication duration and frequency. Novel eye medication delivery methods are being investigated. This medicine administration at the proper place challenges drug delivery systems. Here are innovative ocular drug-delivery methods. Biocompatible liposomes improve drug solubility, stability, absorption, and toxicity. Liposomes affect tear dynamics and medication duration and frequency via interacting with the conjunctiva and cornea. Novel ocular medicine delivery techniques for various eye ailments are being explored. This medication administration at the right place challenges drug delivery systems. Innovative ocular drug-delivery systems will be reviewed here.

The aim of the present research is to study the potential pharmacological activities of herbal extract of Ziziphus and its formulations. It is observed that the plant extracts of different species of Ziziphus have a variety of pharmacological activities. Due to antibiotic resistance, it is necessary to discover new sources of antibiotics. New technologies are used for the development of antimicrobial and antioxidant drugs with enhanced pharmacological activities. Also, scientists are concentrating on herbal medicines because of their numerous advantages over synthetic drugs. Now-a-days many of these herbal formulations, sold over the counter, are not properly standardized for quality and toxicity. In this research work the sub-chronic dermal toxicity study of Ziziphus oenoplia leaf extract containing Carbopol hydrogel formulation is evaluated on adult male Albino Wister rats. Here, the extract containing hydrogel in 3 doses, and 0.9% NaCl solution (negative control) has been applied on the shaved area of dorsolateral trunk of different groups of rats once a day for 28 days for the study. After conduction of the experiment, it has been observed that the control as well as the test groups of animals did not possess any mortality/ morbidity, clinical signs of toxicity or skin reactions such as edema or erythema. There has been no significant change in food consumption or any notable elevation in body weight in the animal groups throughout the experimental period. Thus, in this study the Ziziphus extract incorporated Carbopol hydrogel has been successfully evaluated for dermal toxicity which reveals that the formulation can be safely applied dermally for wound healing purpose.

Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D- alpha -tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50:50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS.

Vitamin K is an essential bioactive compound required for optimal body function. Vitamin K can be present in various isoforms, distinguishable by two main structures, namely, phylloquinone (K1) and menaquinones (K2). The difference in structure between K1 and K2 is seen in different absorption rates, tissue distribution, and bioavailability. Although differing in structure, both act as cofactor for the enzyme gamma-glutamylcarboxylase, encompassing both hepatic and extrahepatic activity. Only carboxylated proteins are active and promote a health profile like hemostasis. Furthermore, vitamin K2 in the form of MK-7 has been shown to be a bioactive compound in regulating osteoporosis, atherosclerosis, cancer and inflammatory diseases without risk of negative side effects or overdosing. This review is the first to highlight differences between isoforms vitamin K1 and K2 by means of source, function, and extrahepatic activity.

Vitamin K and its essential role in coagulation (vitamin K [Koagulation]) have been well established and accepted the world over. Many countries have a Recommended Daily Intake (RDI) for vitamin K based on early research, and its necessary role in the activation of vitamin K-dependent coagulation proteins is known. In the past few decades, the role of vitamin K-dependent proteins in processes beyond coagulation has been discovered. Various isoforms of vitamin K have been identified, and vitamin K2 specifically has been highlighted for its long half-life and extrahepatic activity, whereas the dietary form vitamin K1 has a shorter half-life. In this review, we highlight the specific activity of vitamin K2 based upon proposed frameworks necessary for a bioactive substance to be recommended for an RDI. Vitamin K2 meets all these criteria and should be considered for a specific dietary recommendation intake.

The study was aimed to evaluate the performance of a newly developed non-invasive and non-contact bilirubin measurement device (AJO-Neo) as an alternative to the conventional invasive biochemical method of total serum bilirubin (TSB) estimation in preterm and term neonates suffering from hyperbilirubinemia associated with risk factors, and/or undergoing phototherapy. The safety and efficacy of the device were assessed in 1968 neonates with gestational ages ranging from 28 to 41 weeks and suffering from incidences of hyperbilirubinemia. Linear regression analysis showed a good correlation between AJO-Neo and the conventional method of TSB (Pearson’s coefficient, r  = 0.79). The small bias (0.27 mg/dL) and limits of agreements (− 3.44 to 3.99 mg/dL) were within the range of clinical acceptance. The device was also precise in the measurement of bilirubin levels in all subgroups of the study. The receiver operator curve (ROC), that takes account of both sensitivity and specificity of a device showed high efficacy of the device (area under the curve, AUC = 0.83) in the detection of bilirubin. While monitoring the bilirubin level during phototherapy, the device indicated promising results showing good agreement with TSB. Specificities and sensitivities of the device indicated a much higher accuracy in neonates with associated risk factors for hyperbilirubinemia. Hence, the newly developed device (AJO-Neo) is reliable in measuring bilirubin level in preterm, and term neonates irrespective of gestational or postnatal age, sex, risk factors, feeding behavior or skin color.