The intragastrointestinal fate of paclitaxel-loaded micelles: Implications on oral drug delivery

The goal of the present study is to elucidate the intragastrointestinal fate of micellar delivery systems by monitoring fluorescently labeled different micelles and the model drug paclitaxel (PTX). Both in vitro and ex vivo leakage studies showed fast PTX release in fluids while micelles remained intact, except in fed-state simulated intestinal fluid and fasted-state pig intestinal fluid, thus referring to the intact absorption of micelles and PTX leakage in the gastrointestinal tract with d-α-tocopherol polyethylene glycol 1000 succinate (TPGS) micelles showing higher stability than other micelles. All groups of micelles were absorbed intact in Caco-2 and Caco-2/HT29-MTX cell models and the absorption of TPGS micelles was found to be higher than other micelles. The transport of the micelles across Caco-2/Raji (1.6%–3.5%), Caco-2 (0.8%–1%), and Caco-2/HT29-MTX (0.58%–1%) cell monolayers further verified the absorption of micelles and their subsequent transport; however, more TPGS micelles transported across cell monolayers than other groups. Moreover, the histological examination also confirmed that micelles entered the enterocytes and were transported to basolateral tissues and TPGS showed the stronger ability of penetration than other groups. Thus, these results are succinctly presenting the absorption of intact micelles in GIT confirmed by imaging evidence with prior leakage of the drug, uptake by enterocytes and the transport of micelles that survive the digestion by enterocytes and mainly by microfold cells in material nature dependent way with TPGS showing better results than other groups. In conclusion, these results identify the mechanism by which the gastrointestinal tract processes micelles and point to the likely use of this approach in the design of micelles-based therapies.     

A preliminary study on the development and characterisation of enzymatically grafted P(3HB)-ethyl cellulose based novel composites

In the present study, a novel enzyme-based grafting of poly(3-hydroxybutyrate) [P(3HB)] onto the ethyl cellulose (EC) as a backbone polymer was developed under a mild and ecofriendly environment and laccase was used as a grafting tool. The resulting composites were characterised using various instrumental and imaging techniques. The high intensity of the 3,358 cm^?1 band in the FTIR spectra showed an increase of hydrogen–bonding interactions between P(3HB) and EC at that distinct wavelength region. The morphology was examined by scanning electron microscopy, which showed the well dispersed P(3HB) in the backbone polymer of EC. X-ray diffraction pattern for P(3HB) showed distinct peaks at 2-theta values of 28°, 32°, 34°, 39°, 46°, 57°, 64°, 78° and 84°. In comparison with those of neat P(3HB), the degree of crystallinity for P(3HB)-g-EC decreased. The tensile strength, elongations at break and Young’s modulus of P(3HB)-g-EC reached the highest levels in comparison to the film prepared with pure P(3HB) only, which was too brittle to measure any of the above said characteristics. Results obtained in the present study suggest P(3HB)-g-EC as a potential candidate for various biotechnological applications, such as tissue engineering and packaging.     

Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R² = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.     

Nephroprotective Effects of Alhagi camelorum against Cisplatin-Induced Nephrotoxicity in Albino Wistar Rats

Alhagi camelorum (AC) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The overuse of cisplatin (Cis > 50 mg/m²) is associated with observed nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we investigated the nephroprotective effects of AC plant extract to prevent cisplatin-induced nephrotoxicity in albino Wistar rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and a significantly intense antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It is concluded that co-administration of cisplatin with AC extract showed exceptional nephroprotective effects at a dose of 600 mg/kg for Cis-induced nephrotoxicity.     

Alfvén waves in temperature anisotropic Cairns distributed plasma

The dispersion relations and Landau damping of Alfven waves in kinetic and inertial limits are studied in temperature anisotropic Cairns distributed plasma.In the case of kinetic Alfven waves(KAWs),it is found that the real frequency is enhanced when either the electron perpendicular temperature or the non-thermal parameter A increases.For inertial Alfven waves(IAWs),the real frequency is slightly affected by the electron temperature anisotropy and A.Besides the real frequency,the damping rate of KAWs is reduced when the electron perpendicular temperature or A increases.In the case of IAWs,the temperature anisotropy and A either enhance or reduce the damping rate depending upon the perpendicular wavelength.These results may be helpful to understand the dynamics of KAWs and IAWs in space plasmas where the non-Maxwellian distribution of particles are routinely observed.     

生物催化进展:从计算到代谢工程（英文）

经过数次技术研究和超常创新战略的大发展,生物催化逐渐达到工业化水平,从而受到人们特别的关注.基于酶值,通过生物途径生产高附加值化合物和精细工业化学品成为人们最感兴趣的领域之一.更广泛的众多生物化学路线可由酶催化来实现,其中还有一些酶尚未被人们发现.另一方面,由于非同源底物和某些化学过程所必需的苛刻条件,导致酶催化过程的效率低、稳定性差,因而限制了生物催化的应用.因此,开发具有多催化特征、更高效率和稳定性的绿色催化剂,成为生物催化的重中之重.计算科学、代谢工程、合成生物,以及机器学习路线的运用为新催化剂的工程化提供了新方法.本文重点介绍了合成生物学和代谢工程在催化中的作用,讨论了用于催化的机器学习算法和如何选择一种预测蛋白质-配体相互作用的算法;为了预测键合和催化功能,综述了分子对接的重要性;最后给出了结束语、未来挑战和前景展望.     

Magnetic,Electrical and Thermal Studies of Polypyrrole-Fe<Subscript>2</Subscript>O<Subscript>3</Subscript> Nanocomposites

This research paper comprises of the synthesis of polypyrrole (PPy)-Fe₂O₃ nanocomposites by employing the in situ chemical oxidative polymerization method. The concentration of the filler material was adjusted between 10–50 wt % of PPy. The synthesized nanocomposites were characterized by using X-ray diffraction (XRD). Magnetic analysis and DC electrical conductivity of the samples were carried out using vibrating sample magnetometer (VSM) and two probe DC conductivity method, point towards magnetically active and electrically conductive samples. The magnetic parameters under applied magnetic field demonstrated that the values of coercivity (H _c ), saturation magnetization (M _s ) and remanence (M _r ) can be tailored by carefully controlling the amount of dopant material into the nanocomposites indicating their suitability for controllable switching devices and microwave absorption applications. The DC electrical conductivity showed an increase up to 20 wt % of filler material and thereafter a decrease in the conductivity of nanocomposites with increase in filler content is observed. Thermogravimetric analysis (TGA) showed an increase in thermal stability with an increase in ferrite content in nanocomposites.     

Biotechnological Innovations from Ocean: Transpiring Role of Marine Drugs in Management of Chronic Disorders

Marine drugs are abundant in number, comprise of a diverse range of structures with corresponding mechanisms of action, and hold promise for the discovery of new and better treatment approaches for the management of several chronic diseases. There are huge reserves of natural marine biological compounds, as 70 percent of the Earth is covered with oceans, indicating a diversity of chemical entities on the planet. The marine ecosystems are a rich source of bioactive products and have been explored for lead drug molecules that have proven to be novel therapeutic targets. Over the last 70 years, many structurally diverse drug products and their secondary metabolites have been isolated from marine sources. The drugs obtained from marine sources have displayed an exceptional potential in the management of a wide array of diseases, ranging from acute to chronic conditions. A beneficial role of marine drugs in human health has been recently proposed. The current review highlights various marine drugs and their compounds and role in the management of chronic diseases such as cancer, diabetes, neurodegenerative diseases, and cardiovascular disorders, which has led to the development of new drug treatment approaches.     

Isolation and Identification of Bioactive Compounds from Bidens spp. Using HPLC-DAD and GC-MS Analysis and Their Biological Activity as Anticancer Molecules

The genus Bidens a member of family Compositae, is widely documented as an ethno-medicinally important genus of plants. In the present study, anticancer potential of three ethno-medicinally important species i.e., B. bipinnata, B. biternata and B. pilosa were tested. For in-vitro evaluation, an MTT (Thiazolyl blue tetrazolium bromide) assay was performed against cervical cancer cells (HeLa), hepatocellular carcinoma (HepG), and adenocarcinoma human alveolar basal epithelial cells (A549). For in vivo evaluation, Artemia salina, Danio rerio, and Caenorhabditis elegans were used. Among all the tested extracts, the ethanol extract of B. biternata appeared to have highest anticancer activity, and the compounds responsible for this activity were identified to be Tris (2,4-di-tert-butylphenyl), 4-hydroxy-2,4′-dimethoxychalcone, and 2,4-di-tert-butylphenol. This is the first report of the isolation of Tris (2,4-di-tert-butylphenyl) phosphate from the genus Bidens and the first report of 4-hydroxy-2,4′-dimethoxychalcone and 2,4-di-tert-butylphenol from B. biternata. Among the isolated compounds, 4-hydroxy-2,4′-dimethoxychalcone showed the highest anticancer activity with an LD50 value of 236.7 µg/mL. Therefore, this compound carries promising potential for being established as a pharmaceutical for chemoprevention and chemotherapy.