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Self emulsifying drug delivery systems (SMEDDS) are vital methods to increase bioavailability of poorly soluble drugs by increasing solubility. As oral route is most preferred route of administration due to its painless application and the major problem faced by this route includes decreased bioavailability which lead to importance of evaluation of Self emulsifying drug delivery systems. Self micro emulsifying drug delivery systems especially preferred primarily because these are physically stable, easy to manufacture, can be filled in soft gelatin capsules and then will generate a drug containing micro emulsion with a large surface area upon dispersion in the gastro intestinal tract. Various components like surfactants, lipids, co-surfactants used to formulate self micro emulsifying formulations (droplet size <100nm) which contribute to overall improvement in oral bioavailability via promoting the lymphatic transport, there by hepatic 1st pass metabolism suppressed. The present paper provides information on formulation, physiochemical & bio-pharmaceutical aspects of SMEDDS along with factors affecting & evaluation of SMEDDS. [ABSTRACT FROM AUTHOR]

Cancer is the dangerous disease which caused millions of deaths in worldwide. Enzyme prodrug therapy uses enzymes artificially introduced into the body to convert pro-drugs which have poor biological activity to the active form in the desired location within the body. The use of enzyme pro-drug therapy has gained attention as it has the ability to improve the efficacy and safety of cancer treatment. Chemotherapy for cancer patients has limited success including some drawbacks like systemic toxicity, insufficient drug concentration in tumors. To overcome these drawbacks and improve the cancer treatment the enzyme pro-drug therapy is selected. Enzyme prodrug therapy uses enzymes artificially introduced into the body to convert pro-drugs which have poor biological activity to the active form in the desired location within the body. The selective activation of pro-drugs in tumor tissues by exogenous enzymes for cancer therapy was accomplished by several ways including gene-directed enzyme pro-drug therapy(GDEPT), virus-directed enzyme pro-drug therapy(VDEPT), antibody-directed enzyme pro-drug therapy(ADEPT). Most of these therapies are based on antibody dependent cellular cyto-toxicity, targeted delivery of cytotoxic drugs/tumor site specific activation of prodrugs. This review aims at providing an overview regarding four major systems of GDEPT, ADEPT, VDEPT. Later this review focuses on the bystander effect and combination therapy associated with gene therapy. [ABSTRACT FROM AUTHOR]

The present study examined the potential neuroprotective effects of aloe-emodin (AE) nanoparticles on the cerebral stroke-associated target protein myeloperoxidase (MPO). We investigated the binding interactions between AE and MPO through molecular docking and molecular dynamics simulations. Molecular docking results indicated that AE exhibited a binding energy of -6.9 kcal/mol, whereas it was -7.7 kcal/mol for 2-{[3,5-bis(trifluoromethyl)benzyl]amino}- n -hydroxy-6-oxo-1,6-dihydropyrimidine-5-carboxamide (CCl). Furthermore, molecular dynamics studies demonstrated that AE possesses a stronger binding affinity (-57.137 ± 13.198 kJ/mol) than does CCl (-22.793 ± 30.727 kJ/mol), suggesting that AE has a more substantial inhibitory effect on MPO than does CCl. Despite the therapeutic potential of AE for neurodegenerative disorders, its bioavailability is limited within the body. A proposed hypothesis to enhance the bioavailability of AE is its conversion into aloe-emodin nanoparticles (AENP). The AENPs synthesized through a fabrication method were spherical with a consistent diameter of 104.4 ± 7.9 nm and a polydispersity index ranging from 0.525 to 0.586. In rats experiencing cerebral stroke, there was a notable increase in cerebral infarction size; abnormalities in electrocardiogram (ECG) and electroencephalogram (EEG) patterns; a decrease in brain and cardiac antioxidant activities; and an increase in myeloperoxidase levels compared to those in normal rats. Compared with AE treatment, AENP treatment significantly ameliorated cerebral infarction, normalized ECG and EEG patterns, enhanced brain and cardiac antioxidant activities, and reduced MPO levels in stroke rats. Histopathological evaluations revealed pronounced alterations in the rat hippocampus, with pyknotic nuclei, disarray and loosely packed cells, deterioration of cardiac muscle fibers, and extensive damage to cardiac myocytes, in contrast to those in normal rats. AENP treatment mitigated these pathological changes more effectively than AE treatment in both brain and cardiac cells. These findings support that AENP provides considerable protection against stroke-associated myocardial infarction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The Kisspeptin1 (KISS1)/neurokinin B (NKB)/Dynorphin (Dyn) [KNDy] neurons in the hypothalamus regulate the reproduction stage in human beings and rodents. KNDy neurons co-expressed all KISS1, NKB, and Dyn peptides, and hence commonly regarded as KISS1 neurons. KNDy neurons contribute to the "GnRH pulse generator" and are implicated in the regulation of pulsatile GnRH release. The estradiol (E2)-estrogen receptor (ER) interactions over GnRH neurons in the hypothalamus cause nitric oxide (NO) discharge, in addition to presynaptic GABA and glutamate discharge from respective neurons. The released GABA and glutamate facilitate the activity of GnRH neurons via GABAA-R and AMPA/kainate-R. The KISS1 stimulates MAPK/ERK1/2 signaling and cause the release of Ca 2+ from intracellular store, which contribute to neuroendocrine function, increase apoptosis and decrease cell proliferation and metastasis. The ageing in women deteriorates KISS1/KISS1R interaction in the hypothalamus which causes lower levels of GnRH. Because examining the human brain is so challenging, decades of clinical research have failed to find the causes of KNDy/GnRH dysfunction. The KISS1/KISS1R interactions in the brain have a neuroprotective effect against Alzheimer's disease (AD). These findings modulate the pathophysiological role of the KNDy/GnRH neural network in polycystic ovarian syndrome (PCOS) associated with ageing and, its protective role in cancer and AD. This review concludes with protecting effect of the steroid-derived acute regulatory enzyme (StAR) against neurotoxicity in the hippocampus, and hypothalamus, and these measures are fundamental for delaying ageing with PCOS. StAR could serve as novel diagnostic marker and therapeutic target for the most prevalent hormone-sensitive breast cancers (BCs)., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)