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Derusha Frank,1 Charu Tyagi,1 Lomas Tomar,1 Yahya E Choonara,1 Lisa C du Toit,1 Pradeep Kumar,1 Clement Penny,2 Viness Pillay1 1Department of Pharmacy and Pharmacology, 2Department of Medical Oncology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa Abstract: Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study. Keywords: nanosystems, targeted drug delivery, nanotheranostics, antineoplastic drugs, poor aqueous solubility, solid tumors

Lomas Tomar,1,2 Charu Tyagi,1,3 Manoj Kumar,2 Pradeep Kumar,1 Harpal Singh,2 Yahya E Choonara,1 Viness Pillay11University of the Witwatersrand, Faculty of Health Sciences, Department of Pharmacy and Pharmacology, Johannesburg, Gauteng, South Africa; 2Centre for Biomedical Engineering, Indian Institute of Technology, Delhi, India; 3VSPG College, Chaudhary Charan Singh University, Meerut, IndiaAbstract: Poly(ethylene glycol) (PEG) and polylactic acid (PLA)-based copolymeric nanoparticles were synthesized and investigated as a carrier for prolonged delivery of insulin via the parenteral route. Insulin loading was simultaneously achieved with particle synthesis using a double emulsion solvent evaporation technique, and the effect of varied PEG chain lengths on particle size and insulin loading efficiency was determined. The synthesized copolymer and nanoparticles were analyzed by standard polymer characterization techniques of gel permeation chromatography, dynamic light scattering, nuclear magnetic resonance, and transmission electron microscopy. In vitro insulin release studies performed under simulated conditions provided a near zero-order release pattern up to 10 days. In vivo animal studies were undertaken with varied insulin loads of nanoparticles administered subcutaneously to fed diabetic rabbits and, of all doses administered, nanoparticles containing 50 IU of insulin load per kg body weight controlled the blood glucose level within the physiologically normal range of 90–140 mg/dL, and had a prolonged effect for more than 7 days. Histopathological evaluation of tissue samples from the site of injection showed no signs of inflammation or aggregation, and established the nontoxic nature of the prepared copolymeric nanoparticles. Further, the reaction profiles for PLA-COOH and NH2-PEGDA-NH2 were elucidated using molecular mechanics energy relationships in vacuum and in a solvated system by exploring the spatial disposition of various concentrations of polymers with respect to each other. Incorporation of insulin within the polymeric matrix was modeled using Connolly molecular surfaces. The computational results corroborated the experimental and analytical data. The ability to control blood glucose levels effectively coupled with the nontoxic behavior of the nanoparticles indicates that these nanoparticles are a potential candidate for insulin delivery.Keywords: parenteral delivery, insulin, nanoparticles, poly(lactide-ethylene glycol) diblock copolymer, molecular mechanics energy relationship

This study investigates the extraction, phytochemical screening, and High-Performance Liquid Chromatography (HPLC) estimation of bioactive compounds from Boerhavia diffusa, Kaempferia galanga, and Basella alba. These plants are renowned for their traditional medicinal uses and potential therapeutic properties. The extraction was performed using solvents such as ethanol and methanol, and the extracts were analyzed to identify the presence of key phytochemicals including alkaloids, flavonoids, and saponins through qualitative screening methods. HPLC was employed to quantify specific compounds, providing insights into their concentration and potential therapeutic value. The results revealed distinct profiles of phytochemicals across the plant extracts, with significant quantities of bioactive compounds associated with their medicinal benefits. This comprehensive analysis highlights the pharmacological potential of these plants and supports their continued use in traditional medicine, as well as potential applications in modern therapeutic practices. [ABSTRACT FROM AUTHOR]

The present work reports the influence of selenium replacement by bismuth on the nonlinear optical parameters of ternary Se85-xTe15Bix (x=0, 1, 2, 3, 4, 5 atomic %) chalcogenide thin films. Calculation of nonlinear refractive index (n2), two-photon absorption coefficient (β2) and third-order susceptibility (χ(3)) by well known Z-scan technique with femtosecond laser pulses were done. The Z-scan spectra for Se85-xTe15Bix upto Bi= 4 atomic % results in self-focusing behavior of n2 is positive while for Bi=5 atomic % n2 is negative. The behavior of n2 by using different physical parameters are exlpained. The comparison of experimental and theoretical values of n2 with pure silica are also studied. The presence of the valley at focus in open aperture Z-scan graph demonstrates strong reverse saturable absorption. The figure of merit (FOM) for the Se-Te-Bi chalcogenide thin films is found to be less than 1 and are beneficial for all-optical switch devices. [ABSTRACT FROM AUTHOR]

Ethanolic extract of T. Portulacastrum and pet. Ether extract of M. Laxiflora was evaluated in mice against trinitrobenzene sulfonic acid (TNBS) induced colitis. Mice were pre-treated orally for 14 days and continued for four days after the induction of colitis with (10, 50, and 100 mg/kg). Colitis was induced by intracolonic instillation of 20 mg of TNBS per mice dissolved in 50% alcohol and 4 days later, the colonic mucosal lesion was analyzed along with Diarrhoea, GI transit, defecation, gastric emptying, intestinal fluid accumulation. myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels, reduced glutathione (GSH), and nitric oxide levels in colonic tissue homogenate. Significant reduction in gross damage area, weight loss and decrease in colonic lesion were evident in test substance-pretreated animals dose dependently as compared to samle treated control. These effects were confirmed biochemically by a reduction in colonic myeloperoxidase activity, malondialdehyde levels, nitric oxide levels, and increase in reduced glutathione (GSH) levels. Furthermore, microscopic examination revealed diminution of inflammatory cell infiltration and submucosal edema in colon segments of mice treated with MP and TP . The results demonstrate the protective effect of both sample in the animal model of acute colitis possibly through an antioxidant, anti-lipoperoxidative or due to reduction in nitric oxide generation. [ABSTRACT FROM AUTHOR]

Aromatase is one of the important target for drugs that interfere with production of estrogen in the treatment of estrogen receptor positive breast cancer. Therefore the discovery of novel aromatase inhibitors that can kill the growth of cancer cells selectively with minimal toxic effects on normal healthy cells is desirable. In the present study, novel 5-(4-bromophenyl)-1,3-oxazole derivatives were synthesized, characterized and screened for their biological effect. A series of novel 5-(4-bromophenyl)-1,3-oxazole derivatives OXZ-1 to 12 were docked by Auto Dock tool to evaluate their aromatase inhibition. All the derivatives were synthesized by using versatile and convenient route. Spectroscopic techniques have characterized the synthesized compounds in order to validate their structures. A total of 12 compounds were synthesized and evaluated for their in-vitro aromatase inhibitory activity and all derivatives were tested to assess their cytotoxic effect against breast cancer cell lines (MCF-7). The in vitro cytotoxic activity of the synthesized compounds was determined by MTT assay using MCF7 cell lines. Docking parameters showed that polar (M303, A307 and T310) and nonpolar (A306, M311, F430 and A443) residues were essential for interaction with the aromatase inhibitors. In comparison with the vehicle-treated control Letrozole (IC50 15.83μM), aromatase inhibition activity of synthesized compounds was measured. OXZ-9 demonstrated excellent inhibition with an IC50 value of 14.8μM at 50 percent maximal inhibitory concentration. In vitro cytotoxicity of oxazole derivatives was conducted against MCF7 cell lines by using Cisplatin (IC50 12.46μM) as reference and potent cytotoxic activity was observed for the compounds OXZ-9, OXZ-11, OXZ-8, OXZ-4 and OXZ-3 and their IC50 values were found to be 11.56, 14.63, 17.56, 20.5 and 25.46μM. [ABSTRACT FROM AUTHOR]

Microspheres constitute an important part of oral drug delivery system by virtue of their small size and efficient carrier capacity. However, the success of these microspheres is limited due to their short residence time at the site of absorption. The purpose of the present study was to prepare, characterize and evaluate the colon-targeted microspheres of quercetin for the treatment and management of inflammatory bowel diseases. Microspheres were prepared by the solvent evaporation method using ethyl cellulose and HPMC. Microspheres prepared were coated with eudragit S-100 using an oil-in-oil solvent evaporation method. Eudragit S-100 was used as enteric coating polymer with the aim to release the drug in small intestine. The effect of varying drug/polymer (D/P) ratios on microspheres characteristics were studied by 3² FFD. Desirability function was used to search the optimum formulation. The microspheres prepared were characterized by particle size, zeta potential, polydispersity index, shape and surface morphology, in vitro drug release and stability studies. The results of measurement of mean particle size of formulation F1, F2, and F3 microsphere were found 192±5, 196±4 and 195±6nm respectively. The drug entrapment of different formulations was found as 68.45±0.85, 73.32±0.45 and 65.58±0.35 percentage w/w. The microspheres formed have rough surface and spherical shape as observed in scanning electron microscopy. All values are statistically significant. It was observed that the coated microspheres showed no release in the simulated gastric fluid, negligible release in the simulated intestinal fluid and maximum release in presence of rat caecal content. It was concluded from the study that Eudragit-coated microspheres were promising carriers for colon-targeted delivery of quercetin. [ABSTRACT FROM AUTHOR]

Phytochemical and pharmacological investigations of leaves of Praecitrullus fistulosus for the antidiabetic activity have been done in our research work encompassed in depth and systematic screening of plant leaves and further extraction, characterization and bioevaluation. The research was envisaged for antidiabetic activity of different extracts procured by successive extraction methods and to find out or isolate the most possible active compounds from the active extracts showing the best activity. The antidiabetic activity of all extracts has been evaluated by STZ induced diabetes. The isolated compounds have been evaluated by in-vitro and in-vivo models. The alcohol soluble extractives values were found to be higher than water soluble extractive value. Alcohol being a moderately non polar solvent, able to extract polar and non-polar components yields higher extractive value. The ethanol extract shows significant enhancement in glucose tolerance in glucose fed hyperglycemic normal rats and produced a marked decrease in blood glucose levels at 200 mg/kg and 400 mg/kg body weight in streptozotocin-diabetic rats after 21 days treatment. [ABSTRACT FROM AUTHOR]

In last of 2019, the Centers for Disease Control and Prevention started monitoring the outbreak of a new corona virus, SARS-CoV-2, which causes the respiratory illness now known as COVID-19. Authorities first identified the virus in Wuhan, China. More than 82542 case of Corona virus in China at 31 March 2020. Health authorities have identified many other people with COVID-19 around the world. On 31 March 2020, the virus spread more than 750890 People in the World. The World Health Organization (WHO) has declared a public health emergency relating to COVID-19. Since then, this strain has been diagnosed in several residents of world. The CDC have advised that it is likely to spread to more people. COVID-19 has affected at least 213 countries or territories or areas. The first people with COVID-19 had links to an animal and seafood market. This fact suggested that animals initially transmitted the virus to humans. However, people with a more recent diagnosis had no connections with or exposure to the market, confirming that humans can pass the virus to each other. Corona viruses will infect most people at some time during their lifetime. Corona viruses can mutate effectively, which makes them so contagious. Information on the virus is scarce at present. In the past, respiratory conditions that develop from corona viruses, such as SARS and MERS, have spread through close contacts. On 17 February 2020, the Director-General of the WHO presented at a media briefing the following updates on how often the symptoms of COVID-19. However, while some viruses are highly contagious, it is less clear how rapidly corona viruses will spread. Symptoms vary from person-toperson with COVID-19. It may produce few or no symptoms. However, it can also lead to severe illness and may be fatal. On 11 March 2020, WHO declared Novel Corona virus Disease (COVID-19) outbreak as a Pandemic. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common types of cancer in females. Therefore, development of potent Aromatase inhibitors (AIs) becomes important which are clinically active against estrogen production in postmenopausal women and thereby on breast cancer. Oxazole analogues can be used as non steroidal aromatase inhibitors for breast cancer therapy. Totally twenty four compounds were synthesized and evaluated for their aromatase inhibitory activity and selected derivatives were tested against breast cancer cell lines (MCF-7) to evaluate their cytotoxic effect. All the novel Phenyl[3-(1,3-oxazol-5-yl)phenyl]carbamate derivatives were docked by Auto Dock software and after screening the compounds were synthesized and characterized by FTIR, mass and NMR spectroscopy. The docking parameters revealed that polar (T310, L477, V369 and V370) and non-polar (A306, A307, M303, F430, V370 and L152) residues of aromatase were essential for interacting with the newly synthesized aromatase inhibitors. Aromatase inhibition activity of the synthesized compounds were calculated in comparison with vehicle-treated control Letrozole (IC50 16.7μM). OXA-19 showed excellent inhibition having 50% inhibitory concentration IC50 value 15.6μM. In-vitro cytotoxic activity of ten selected derivatives was performed against MCF7 cancer cell lines taking Cisplatin as reference and compounds OXA-6, OXA-11, OXA-12, OXA-18, OXA-19 and OXA-22 exhibited potent cytotoxic activity and their IC50 values were found to be 21.13, 19.3, 15.56, 16.76, 11.8 and 13.7μM respectively. Therefore to discover novel aromatase inhibitors and to find a potent anti-breast cancer drug, we have designed and synthesized a novel series of oxazole derivatives. [ABSTRACT FROM AUTHOR]

The aim of present study was to formulate & evaluate the mucoadhesive sustained release formulations of lamivudine and to fulfill this aim, two mucoadhesive formulations Gels and Tablets were prepared by using three different polymers: HPMC K15, poloxamer 407 & carbopol 934. Three mucoadhesive gel and nine tablet formulations were prepared and evaluated for various parameters. All three gels were able to give sustained release up to 12 hours. Tablet formulations, F1 to F5 failed to fulfill the aim. Only F6, F7, F8 & F9 formulations were selected, as all gave sustained release up to 12 hours, except F6, which gave sustained release profile only till 7 hours. From the drug release plots, it was concluded that the type of polymer and concentration of polymer have distinct effect on in vitro drug release profile and all the formulations follow first order mechanism with anomalous diffusion or non-fickian diffusion, except carbopol gel and poloxamer tablets. Carbopol gel follows zero order release rate with super case II transport and poloxamer tablets (F6) follow higuchi with non -fickian diffusion. It is concluded that mucoadhesive formulations of lamivudine can be prepared for sustaining its release. And the successful outcome of the present study also encourage for further studies to assess the ability of the mucoadhesive formulations of lamivudine in providing an effective sustained and safe therapy for AIDS. [ABSTRACT FROM AUTHOR]