Promising drug delivery approaches to treat microbial infections in the vagina: a recent update

An optimal host–microbiota interaction in the human vagina governs the reproductive health status of a woman. The marked depletion in the beneficial Lactobacillus sp. increases the risk of infection with sexually transmitted pathogens, resulting in gynaecological issues. Vaginal infections that are becoming increasingly prevalent, especially among women of reproductive age, require an effective concentration of antimicrobial drugs at the infectious sites for complete disease eradication. Thus, topical treatment is recommended as it allows direct therapeutic action, reduced drug doses and side effects, and self-insertion. However, the alterations in the physiological conditions of the vagina affect the effectiveness of vaginal drug delivery considerably. Conventional vaginal dosage forms are often linked to low retention time in the vagina and discomfort which significantly reduces patient compliance. The lack of optimal prevention and treatment approaches have contributed to the unacceptably high rate of recurrence for vaginal diseases. To combat these limitations, several novel approaches including nano-systems, mucoadhesive polymeric systems, and stimuli-responsive systems have been developed in recent years. This review discusses and summarises the recent research progress of these novel approaches for vaginal drug delivery against various vaginal diseases. An overview of the concept and challenges of vaginal infections, anatomy and physiology of the vagina, and barriers to vaginal drug delivery are also addressed

Advancement on sustained antiviral ocular drug delivery for herpes simplex virus keratitis: recent update on potential investigation

The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs’ poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended

Therapeutic health booster: seaweeds against several maladies

538-546Seaweeds (marine macro algae) are extremely important oceanic resource having unique secondary metabolites. They have the potential for supporting industrial development as being source of many essential substances such as pharmaceuticals, cosmetics, nutritional supplements etc. Seaweeds offer a wide range of therapeutic possibilities was established only some decades ahead. Several pharmacologically important metabolites have been discovered from seaweeds in recent years, the exploitation of seaweeds for therapeutically active molecules is still in its embryonic stage. In order to harness the rich therapeutic potential of seaweeds the present limited use needs to be diversified into several applications. Present review highlights a state of art on the medicinal value of seaweeds and their exploitation scenario on a global scale

Multiple Biological Effects of an Iridoid Glucoside, Catalpol, and Its Underlying Molecular Mechanisms

Catalpol, an iridoid glucoside, is widely distributed in many plant families and is primarily obtained from the root of Rehmannia glutinosa Libosch. Rehmannia glutinosa is a plant very commonly used in Chinese and Korean traditional medicine for various disorders, including diabetes mellitus, neuronal disorders, and inflammation. Catalpol has been studied extensively for its biological properties both in vitro and in vivo. This review aims to appraise the biological effects of catalpol and their underlying mechanisms. An extensive literature search was conducted using the keyword “Catalpol” in the public domains of Google scholar, PubMed, and Scifinder. Catalpol exhibits anti-diabetic, cardiovascular protective, neuroprotective, anticancer, hepatoprotective, anti-inflammatory, and anti-oxidant effects in experimental studies. Anti-inflammatory and antioxidant properties are mostly related for its biological effect. However, some specific mechanisms are also elucidated. Elevated serotonin and BDNF level by catalpol significantly protect against depression and neurodegeneration. Catalpol demonstrated an increased mitochondrial biogenesis and activation of PI3K/Akt pathway for insulin sensitizing effect. Further, its cardiovascular protective effect was linked to PI3K/Akt, apelin/APJ and Jak-Stat pathway. Catalpol produced a significant reduction in cell proliferation and an increase in apoptosis in different cancer conditions. Overall, catalpol demonstrated multiple biological effects due to its numerous mechanisms including anti-inflammatory and antioxidant effects

Artificial Intelligence in Pharmaceutical and Healthcare Research

Artificial intelligence (AI) is a branch of computer science that allows machines to work efficiently, can analyze complex data. The research focused on AI has increased tremendously, and its role in healthcare service and research is emerging at a greater pace. This review elaborates on the opportunities and challenges of AI in healthcare and pharmaceutical research. The literature was collected from domains such as PubMed, Science Direct and Google scholar using specific keywords and phrases such as ‘Artificial intelligence’, ‘Pharmaceutical research’, ‘drug discovery’, ‘clinical trial’, ‘disease diagnosis’, etc. to select the research and review articles published within the last five years. The application of AI in disease diagnosis, digital therapy, personalized treatment, drug discovery and forecasting epidemics or pandemics was extensively reviewed in this article. Deep learning and neural networks are the most used AI technologies; Bayesian nonparametric models are the potential technologies for clinical trial design; natural language processing and wearable devices are used in patient identification and clinical trial monitoring. Deep learning and neural networks were applied in predicting the outbreak of seasonal influenza, Zika, Ebola, Tuberculosis and COVID-19. With the advancement of AI technologies, the scientific community may witness rapid and cost-effective healthcare and pharmaceutical research as well as provide improved service to the general public

Molecular and Biochemical Pathways of Catalpol in Alleviating Diabetes Mellitus and Its Complications

Catalpol isolated from Rehmannia glutinosa is a potent antioxidant and investigated against many disorders. This review appraises the key molecular pathways of catalpol against diabetes mellitus and its complications. Multiple search engines including Google Scholar, PubMed, and Science Direct were used to retrieve publications containing the keywords “Catalpol”, “Type 1 diabetes mellitus”, “Type 2 diabetes mellitus”, and “diabetic complications”. Catalpol promotes IRS-1/PI3K/AKT/GLUT2 activity and suppresses Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose 6-phosphatase (G6Pase) expression in the liver. Catalpol induces myogenesis by increasing MyoD/MyoG/MHC expression and improves mitochondria function through the AMPK/PGC-1α/PPAR-γ and TFAM signaling in skeletal muscles. Catalpol downregulates the pro-inflammatory markers and upregulates the anti-inflammatory markers in adipose tissues. Catalpol exerts antioxidant properties through increasing superoxide dismutase (sod), catalase (cat), and glutathione peroxidase (gsh-px) activity in the pancreas and liver. Catalpol has been shown to have anti-oxidative, anti-inflammatory, anti-apoptosis, and anti-fibrosis properties that in turn bring beneficial effects in diabetic complications. Its nephroprotective effect is related to the modulation of the AGE/RAGE/NF-κB and TGF-β/smad2/3 pathways. Catalpol produces a neuroprotective effect by increasing the expression of protein Kinase-C (PKC) and Cav-1. Furthermore, catalpol exhibits a cardioprotective effect through the apelin/APJ and ROS/NF-κB/Neat1 pathway. Catalpol stimulates proliferation and differentiation of osteoblast cells in high glucose condition. Lastly, catalpol shows its potential in preventing neurodegeneration in the retina with NF-κB downregulation. Overall, catalpol exhibits numerous beneficial effects on diabetes mellitus and diabetic complications

Development of In-Situ Spray for Local Delivery of Antibacterial Drug for Hidradenitis Suppurativa: Investigation of Alternative Formulation

Hidradenitis suppurativa (HS) has been considered an orphan disease with limited treatments available. The available topical treatment for this condition is clindamycin lotion; however, short retention and frequent application are the main setbacks. Thus, the present study aimed to attain an optimized antibacterial in situ spray formulation for the hidradenitis suppurativa skin condition, which gels once in contact with the skin surface at around 37 °C and possesses bioadhesion as well as sustained-release properties of the incorporated drug. Different concentrations of thermo-reversible gelling polymer, Pluronic F-127, were investigated along with the selected bioadhesive polymers, HPMC and SA. The optimized formulation F3 consisting of 18% Pluronic F-127 with 0.2% HPMC and 0.2% SA was characterized based on various physicochemical properties. The gelation temperature of F3 was found to be 29.0 ± 0.50 °C with a gelation time of 1.35 ± 0.40 min and a pH of 5.8. F3 had the viscosity of 178.50 ± 5.50 cP at 25 °C and 7800 ± 200 cP at 37 °C as the gel set. The optimized formulation was found to be bioadhesive and cytocompatible. Cumulative drug release was 65.05% within the time-frame of 8 h; the release pattern of the drug followed zero-order kinetics with the Higuchi release mechanism. The average zone of inhibition was found to be 43.44 ± 1.34 mm. The properties of F3 formulation reflect to improve residence time at the site of application and can enhance sustained drug release. Therefore, it could be concluded that optimized formulation has better retention and enhanced antimicrobial activity for superior efficacy against HS

Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery

The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery

Effect of madecassoside in reducing oxidative stress and blood glucose in streptozotocin–nicotinamide-induced diabetes in rats

Objectives Madecassoside (MAD) is a triterpenoid constituent of Centella asiatica (L.) Urb., an ethnomedical tropical plant, extracts of which were shown to reduce blood glucose in experimental diabetes. This study examines MAD for its anti-hyperglycaemic effects and tests the hypothesis that it reduces the blood glucose in experimentally induced diabetic rats by protecting the β-cells. Methods Diabetes was induced using streptozotocin (60 mg/kg, i.v.) followed by nicotinamide (210 mg/kg, intraperitoneal (i.p.)). MAD (50 mg/kg) was administered orally for 4 weeks, commencing 15 days after induction of diabetes; resveratrol (10 mg/kg) was used as a positive control. Fasting blood glucose, plasma insulin, HbA1c, liver and lipid parameters were measured, along with antioxidant enzymes and malondialdehyde as an index of lipid peroxidation; histological and immunohistochemical studies were also undertaken. Key findings MAD normalized the elevated fasting blood glucose levels. This was associated with increased plasma insulin concentrations. MAD alleviated oxidative stress by improving enzymatic antioxidants and reducing lipid peroxidation. Histopathological examination showed significant recovery of islet structural degeneration and an increased area of islets. Immunohistochemical staining showed increased insulin content in islets of MAD-treated rats. Conclusions The results demonstrate an antidiabetic effect of MAD associated with preservation of β-cell structure and function