Silybin, is one imminent therapeutic for drug induced hepatotoxicity, human prostrate adenocarcinoma and other degenerative organ diseases. Recent evidences suggest that silybin influences gluconeogenesis pathways favorably and is beneficial in the treatment of type 1 and type 2 diabetes. The compound however is constrained due to solubility (0.4 mg/mL) and bioavailabilty limitations. Appropriate nanoparticle design for silybin in biocompatible polymers was thus proposed as a probable solution for therapeutic inadequacy. New surface engineered biopolymeric nanoparticles with high silybin encapsulation efficiency of 92.11% and zeta potential of +21 mV were designed. Both the pure compound and the nanoparticles were evaluated in vivo for the first time in experimental diabetic conditions. Animal health recovered substantially and the blood glucose levels came down to near normal values after 28 days treatment schedule with the engineered nanoparticles. Restoration from hyperglycemic damage condition was traced to serum insulin regeneration. Serum insulin recovered from the streptozotocin induced pancreatic damage levels of 0.17±0.01 µg/lit to 0.57±0.11 µg/lit after nanoparticle treatment. Significant reduction in glycated hemoglobin level, and restoration of liver glycogen content were some of the other interesting observations. Engineered silybin nanoparticle assisted recovery in diabetic conditions was reasoned due to improved silybin dissolution, passive transport in nanoscale, and restoration of antioxidant status.
Wound healing is an innate physiological response that helps restore cellular and anatomic continuity of a tissue. Selective biodegradable and biocompatible polymer materials have provided useful scaffolds for wound healing and assisted cellular messaging. In the present study, guar gum, a polymeric galactomannan, was intrinsically modified to a new cationic biopolymer guar gum alkylamine (GGAA) for wound healing applications. Biologically synthesized silver nanoparticles (Agnp) were further impregnated in GGAA for extended evaluations in punch wound models in rodents. SEM studies showed silver nanoparticles well dispersed in the new guar matrix with a particle size of ~18 nm. In wound healing experiments, faster healing and improved cosmetic appearance were observed in the new nanobiomaterial treated group compared to commercially available silver alginate cream. The total protein, DNA, and hydroxyproline contents of the wound tissues were also significantly higher in the treated group as compared with the silver alginate cream (P < 0.05). Silver nanoparticles exerted positive effects because of their antimicrobial properties. The nanobiomaterial was observed to promote wound closure by inducing proliferation and migration of the keratinocytes at the wound site. The derivatized guar gum matrix additionally provided a hydrated surface necessary for cell proliferation.
Engineered nanoparticles loaded with AG provided a fast protection in APAP induced acute liver failure.
Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps) were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100® polymer (Rohm Pharma GmbH, Darmstadt, Germany). Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 μmol/g in hepatic tissue due to Smnps.
Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic- co -glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery.
Leishmaniasis is a neglected tropical disease caused by a protozoan parasite of the genus Leishmania. Visceral leishmaniasis is the most severe type and is transmitted by the phlebotomine sandflies of genera Lutzomyia (New World) or Phlebotomus (Old World) to human and other vertebrates. Leishmaniasis is widespread in developing countries with current mortality rate of 50 thousand deaths per year. The parasites adopt different biochemical approaches to evade the host immune system. Knowledge in chemical control of leishmaniasis is currently emerging and not many drugs are available. Control of parasite is complex and WHO has put an ardent appeal for development of drugs and delivery devices against leishmaniasis. Mainstay in treatment of leishmaniasis is pentavalent antimonials but second-line drugs like amphotericin B and pentamidine are available. Clinical acceptability of drugs is poor due to severe toxicity, poor bioavailability, improper localization and recent appearance of resistant variants. Interest in leishmanicidal chemotherapy is therefore renewed and biochemical strategies or improved delivery appear to be a solution. Trends in control of leishmaniasis also include specific applications of low-cost, locally available plant drugs in different delivery devices. This work attempts to present a comprehensive overview of the different approaches to targeted leishmanicidal chemotherapy.
'Supercritical fluid' describes a gas or liquid at conditions above its critical point. A greater range of solvent properties can be achieved with Supercritical fluid as a single solvent by careful manipulation of temperature and pressure at the supercritical state. Supercritical fluids are attractive media for several chemical reactions having better control over the reaction rates in different areas of biochemistry, polymer chemistry and environmental science. Supercritical fluid extraction (SFE), a rapid, convenient, efficient, and selective method has been used successfully for the separation of analytes prior to supercritical fluid chromatography (SFC), which is a relatively recent chromatographic technique and is commercially available since 1982. SFC significantly reduces the usage of organic solvents and wastes by using supercritical CO 2 as the mobile phase. The important principles of green chemistry that are applicable to green chromatography includes prevention of waste, use of safer solvents and increasing energy efficiency. All these factors are taken care of in SFC which combines some of the best features of HPLC as well as GC. Analytes that cannot be vaporized for analysis by gas chromatography or have no functional groups for detection by the usual liquid chromatography techniques, can be separated and detected using SFC. By now SFC has been applied to wide variety of materials including natural products, pharmaceuticals, foods, pesticides, herbicides, surfactants, polymers and polymer additives, heavy metals, fossils fuels, petroleum, explosives and propellants. SFC has now become an attractive alternative for chiral drug separation.
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