ABSTRACT
PURPOSE: Metformin is the most commonly prescribed drug in the management of metabolic disorders such as polycystic ovarian syndrome (PCOS) and gestational diabetes in women of reproductive age. Insulin-sensitizing effect of metformin helps in improving from PCOS features such as hyperandrogenism, anovulation, and infertility. However, its ability to cross placental barrier raises concern about safety of the drug on early embryonic development. In this study, we evaluated the effect of metformin on the ovarian function and embryo development. METHODS: Adult Swiss albino female mice were administered with metformin (0, 50, 100, and 200 mg/kg body weight) for 4 weeks and assessed for reproductive function and preimplantation embryo development. Further, effect of metformin (0, 10, 25, 50, 100, 250, and 500 µg/mL) exposure to 2-cell-stage embryos was tested under in vitro conditions. RESULTS: Metformin did not alter the body weight, blood glucose, ovarian weight, and follicular reserve. However, the early embryo development was significantly affected in mice treated with metformin in vivo at highest dose. Moreover, embryos which were exposed to metformin in vitro showed dose-dependent decline in blastocyst rate and hatching rate. Furthermore, at highest concentration of metformin (500 µg/mL), all the embryos were arrested at compaction stage. CONCLUSION: The study revealed that metformin affects the early embryonic development and raises concern about its use during conception.
Subject(s)
Diabetes, Gestational/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Polycystic Ovary Syndrome/drug therapy , Adult , Animals , Blastocyst/drug effects , Blood Glucose/drug effects , Diabetes, Gestational/blood , Diabetes, Gestational/physiopathology , Disease Models, Animal , Embryonic Development/drug effects , Female , Fertilization in Vitro/trends , Humans , Hypoglycemic Agents/adverse effects , Insulin/metabolism , Insulin Resistance/genetics , Metformin/adverse effects , Mice , Polycystic Ovary Syndrome/blood , Polycystic Ovary Syndrome/physiopathology , PregnancyABSTRACT
With growing interest in polymers of natural origin, innumerable polysaccharides have gained attention for their biomedical application. Pullulan, one of the FDA approved nutraceuticals, possesses multiple unique properties which make them highly advantageous for biomedical applications. This present review encompasses the sources, production, properties and applications of pullulan. It highlights various pullulan based stimuli-responsive systems (temperature, pH, ultrasound, magnetic), subcellular targeted systems (mitochondria, Golgi apparatus/endoplasmic reticulum, lysosome, endosome), lipid-vesicular systems (solid-lipid nanoparticles, liposomes), polymeric nanofibres, micelles, inorganic (SPIONs, gold and silver nanoparticles), carbon-based nanoplatforms (carbon nanotubes, fullerenes, nanodiamonds) and quantum dots. This article also gives insight into different biomedical, therapeutic and diagnostic applications of pullulan viz., imaging, tumor targeting, stem cell therapy, gene therapy, vaccine delivery, cosmetic applications, protein delivery, tissue engineering, photodynamic therapy and chaperone-like activities. The review also includes the toxicological profile of pullulan which is helpful for the development of suitable delivery systems for clinical applications.
Subject(s)
Biomedical Engineering , Biosensing Techniques , Glucans/chemistry , Nanoparticles/chemistry , Biodegradation, Environmental , Biomedical Engineering/methods , Chemistry Techniques, Synthetic , Drug Carriers/chemistry , Drug Compounding , Drug Delivery Systems , Electric Conductivity , Endosomes , Glucans/biosynthesis , Glucans/toxicity , Hydrogen-Ion Concentration , Liposomes , Molecular Targeted Therapy , Nanotechnology , Oxidation-Reduction , TemperatureABSTRACT
AIM: To prepare nanostructured lipid carriers (NLCs) loaded with asenapine maleate (ASPM) to increase its oral bioavailability by intestinal lymphatic uptake. MATERIALS & METHODS: ASPM-NLCs were prepared by ultrasound dispersion technique, by adopting Design of Experiment approach, and characterized. RESULTS: The optimized formulation exhibited good physicochemical parameters. Differential scanning calorimetry and x-ray diffraction studies indicated the amorphized nature of ASPM in lipid matrix. In vitro drug release study indicated the sustained release of drug from NLCs. ASPM-NLCs showed greater permeability across Caco2 cells and everted rat ileum. ASPM-NLCs showed greater cellular uptake, superior preclinical oral bioavailability and higher efficacy in reducing the L-DOPA-carbidopa-induced locomotor count compared with plain drug. CONCLUSION: ASPM-NLCs were successfully developed that showed enhanced performance both in vitro and in vivo.