KETAMINE-IN OIL-IN-WATER MULTIPLE EMULSION FOR PROLONGED DRUG RELEASE

A preparation of Ketamine [2-(Chlorophenyl)-2-(methylamino) cyclohexanone, C₁₃H₁₆ClNO, anesthetic agent] in oil in water multiple emulsion for prolonged drug release was formulated and evaluated. Ketamine, the cyclohexylamine, is used as a short-acting anaesthetic in humans and in some animal species [1]. Ketamine is poorly bound to plasma proteins and has a half-life of approximately 4 hours following intravenous injection [2]. Ketamine leaves the blood very rapidly to be distributed into the tissues with a high lipid solubility [2]. The recommended dosage of intravenous Ketamine is 2.5-20mg/kg [3]. The LD50 injected intraperitoneally in mice and rats is 100 times the intravenous and 30 times the intramuscular dose used in humans.

The objective of this study was to test the concept that a multiple emulsion could be formulated which has high porosity and lower viscosity at 37°C consistent with its intended use for sustained drug release and to prolong the half-life of the anesthesia. The results showed that the Ketamine (100mg/ml in inner phase) released 8.2% at 10 minutes, 67.0% at 30 minutes, and 95.5% at 60 minutes from the Ketamine/O/W multiple emulsion in a well-controlled manner.     

Modification of isotactic polypropylene film by radiation-induced graft copolymerization

In the present communication we report on the radiation induced grafting of methyl methacrylate (MMA) onto irradiated isotactic polypropylene film (IPP) by Peroxidation method to prepared grafted membrane (IPP-g-MMA). The radioactive isotope ⁶⁰Co was used as the source of gamma radiation. A plausible mechanism of grafting has been proposed. Optimum conditions pertaining to maximum percentage of grafting were evaluated as a function of different reaction parameters such as radiation dose, inhibitor concentration, monomer concentration, reaction time and reaction temperature respectively. Maximum percentage of grafting (85%) was obtained at [radiation dose] = 25 kGy, [inhibitor concentration] = 0.04 wt%, [MMA] = 6 wt%, [Reaction Temperature] = 60 °C in a [Reaction time] of 120 min. The evidence of grafted membrane was characterized by Fourier transform infrared spectroscopy, Atomic force microscopy method, Scanning electron microscopy which indicates that MMA has been grafted onto IPP. Hydrolysis of the grafted membranes in 1 N NaOH transformed ester groups of the grafted membranes to carboxylic acid and hydroxyl groups to form hydrolyzed grafted membranes. Hydrolyzed grafted membranes were investigated for their swelling behavior. Swelling properties of the hydrolyzed grafted membranes were performed in different solvents such as water, N,N-dimethylformamide (DMF) and dimethylsulfoxide (DMSO). Maximum percentage swelling value of IPP-g-MMA was observed in pure DMSO, followed by DMF and water.     

Combinatorial Mapping of Surface Energy Effects on Diblock Copolymer Thin Film Ordering

Combinatorial gradient techniques are used to map the morphology dependence of thin symmetric diblock copolymer films on film thickness and substrate surface energy. An inversion from symmetric to anti‐symmetric lamellar morphology occurs with a progressive change in surface energy. An intermediate neutral region is found between these limiting types of ordering. The width ω of this transitional energy range scales as a power of copolymer mass M, ω ∝ M^1.9.

Optical photograph of a combinatorial map of the thin‐film block‐copolymer morphology on a film thickness and surface energy gradient. Island and holes on the surface scatter light causing the film to appear cloudy (lighter in color) in the areas where they exist. The darker areas do not have surface features and do not scatter light.     

Biochemical and Biophysical Characterisation of the Hepatitis E Virus Guanine-7-Methyltransferase

Hepatitis E virus (HEV) is an understudied pathogen that causes infection through fecal contaminated drinking water and is prominently found in South Asian countries. The virus affects ~20 million people annually, leading to ~60,000 infections per year. The positive-stranded RNA genome of the HEV genotype 1 has four conserved open reading frames (ORFs), of which ORF1 encodes a polyprotein of 180 kDa in size, which is processed into four non-structural enzymes: methyltransferase (MTase), papain-like cysteine protease, RNA-dependent RNA polymerase, and RNA helicase. MTase is known to methylate guanosine triphosphate at the 5′-end of viral RNA, thereby preventing its degradation by host nucleases. In the present study, we cloned, expressed, and purified MTase spanning 33–353 amino acids of HEV genotype 1. The activity of the purified enzyme and the conformational changes were established through biochemical and biophysical studies. The binding affinity of MTase with magnesium ions (Mg²⁺) was studied by isothermal calorimetry (ITC), microscale thermophoresis (MST), far-UV CD analysis and, fluorescence quenching. In summary, a short stretch of nucleotides has been cloned, coding for the HEV MTase of 37 kDa, which binds Mg²⁺ and modulate its activity. The chelation of magnesium reversed the changes, confirming its role in enzyme activity.     

Organocatalyzed Double C(sp3)−H Alkylation of Cyclic N-Sulfonyl Ketimines with 3-Chloropropiophenones: Selective Access to 2,3,6-Trisubstituted Pyridines

An efficient sequential one-pot, two-step pseudo-four-component reaction between 3/4-methyl N-sulfonyl ketimines with 3-chloropropiophenones triggered by DIPEA/NaHCO₃ as a cooperative base and subsequent aza-cyclization using NH₄OAc is reported. This transition-metal-oxidant-free technique concocts new C−C/C=C/C=N−C bonds selectively, guaranteeing acceptable yields of 2,3,6-trisubstituted pyridines possessing ortho-hydroxyaryl/benzenesulfonamide and propiophenone moieties at C2 and C3 positions, respectively. Interestingly, while replacing methyl-substituents with straight alkyl chains of N-sulfonyl ketimines, only a monoalkylation reaction happened with in situ-generated vinyl ketones to deliver promising yields of 3-picoline derivatives. Moreover, the synthetic transmutation of prepared pyridine derivative led to several important classes of pyridocoumarin, 5H-chromenopyridine, and di(pyridin-3-yl) methane derivatives.