Bifunctional Polysulfone-Chitosan Composite Hollow Fiber Membrane for Bioartificial Liver.

Hollow fiber membranes are widely used as assist devices for bioartificial liver application. Asymmetric porous polysulfone and polysulfone-tocopheryl polyethylene glycol succinate (Psf-TPGS) composite hollow fiber and flat membranes were prepared by phase inversion procedure and subsequently surface modified with chitosan using sulfonation with concentrated sulfuric acid. Sulfonation induces negative charge on the prepared membrane surface and facilitates the attachment of chitosan amine groups by electrostatic interaction. The surface modification of membrane is stable at room temperature as dictated by presence of nitrogen in XPS analysis and amide linkages in FT-IR spectra. Further, biological studies of the membranes were performed using HepG2 cell line. Chitosan is biocompatible and shows structural similarity to glycosaminoglycans, a native liver ECM component. The chitosan-modified composite Psf and Psf-TPGS membranes have shown enhanced attachment and proliferation of HepG2 cells on outer surface as confirmed by the cell counting, DNA content, confocal microscopy, and SEM micrographs. The cells form a 3D multicellular spheroid structure on the chitosan-modified membranes in significantly larger number as seen in the SEM micrographs. Also, the hemocompatibility of the modified composite membranes were comparable to the unmodified membranes. Thus, the chitosan-modified composite membranes we have developed are bifunctional and have the potential to be used in bioartifical liver application.

Synthesis of meso-pyrrole-substituted 22-oxacorroles by a "3+2" approach.

Unsymmetrical 22-oxacorrole containing two aryl groups and one pyrrole group at the meso position was synthesized by condensing one equivalent of 16-oxatripyrrane with one equivalent of meso aryl dipyromethane under mild acid-catalyzed conditions followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). This [3+2] condensation approach was expected to yield meso-free 25-oxasmaragdyrin but unexpectedly afforded unsymmetrical meso-pyrrole-substituted 22-oxacorrole. We demonstrated the versatility of the reaction by synthesizing four new meso-pyrrole-substituted 22-oxacorroles. The reactivity of α-position of meso-pyrrole was tested by carrying out various functionalization reactions such as bromination, formylation, and nitration and obtained the functionalized meso-pyrrole-substituted 22-oxacorroles in decent yields. The X-ray structure obtained for one of the functionalized meso-pyrrole substituted 22-oxacorrole revealed that the macrocycle was nearly planar and the meso-pyrrole was in the perpendicular orientation with respect to the macrocyclic plane. The meso-pyrrole-substituted 22-oxacorroles absorb strongly in 400-700 nm region with one strong Soret band and four weak Q bands. The 22-oxacorroles are strongly fluorescent and showed emission maxima at ≈650 nm with decent quantum yields and singlet-state lifetimes. The 22-oxacorroles are redox-active and exhibited three irreversible oxidations and one or two reversible reduction(s). A preliminary biological study indicated that meso-pyrrole corroles are biocompatible.

Carboplatin loaded polymethylmethacrylate nano-particles in an adjunctive role in retinoblastoma: an animal trial.

PURPOSE: The purpose of the study is to compare the intra-vitreal concentrations of carboplatin, post peri-ocular injections of commercially available carboplatin (CAC) and a novel carboplatin loaded polymethylmethacrylate nanoparticulate carboplatin (NPC), in either eye, as a model system for treatment of advanced intra-ocular retinoblastoma (RB). DESIGN: Experimental, comparative, animal study. MATERIALS AND METHODS: Polymethylmethacrylate nanoparticles were prepared by free radical emulsion polymerization of methyl methacrylate in aqueous solution of carboplatin in the presence of surfactant sodium dodecyl sulfate and thermal initiator ammonium persulfate. 21 Sprague-Dawley rats, aged between 6 weeks and 3 months were enrolled. The right eye of each rat was injected peri-ocularly with CAC formulation (1 ml of 10 mg/ml) and the left eye with NPC (1 ml of 10 mg/ml), post-anesthesia, by an ophthalmologist trained in ocular oncology. Three rats each were euthanized on days 1, 3, 5, 7, 14, 28 and 42, post-injection and both eyes were carefully enucleated. Intra-vitreal concentrations of CAC and NPC were determined with Inductively Coupled Plasma Atomic Emission Spectroscopy. Analysis of data was done with paired t-test. RESULTS: The intra-vitreal concentration of carboplatin with NPC was ~3-4 times higher than with CAC in all animals, on all the days (P < 0.05). CONCLUSION: A higher trans-scleral permeability gradient is obtained with the novel nanoparticles than with the commercial drug, leading to sustained higher levels of carboplatin in the vitreous. Peri-ocular injection of NPC could thus have an adjuvant efficacy in the treatment for advanced clinical RB, specifically those with vitreous seeds.

In vivo intraocular distribution and safety of periocular nanoparticle carboplatin for treatment of advanced retinoblastoma in humans.

PURPOSE: To study the intraocular distribution and safety of polymethylmethacrylate nanoparticles loaded with carboplatin after posterior subtenon injection in humans. DESIGN: Prospective, interventional, comparative case series. METHODS: Six patients (mean age: 26.83 ± 7.5 years), scheduled to undergo planned uniocular enucleation in an institutional setting, were randomly divided into 3 groups. Each group received a 10 mg/mL posterior subtenon injection of nanoparticle carboplatin in the eye to be enucleated. Two eyes were enucleated 6, 24 and 72 hours post injection. Intravenous blood was collected during enucleation. The concentration of carboplatin reaching various intraocular tissues was determined by inductively coupled plasma atomic emission spectroscopy. The drug toxicity in the ocular tissues was assessed by histopathology and high-resolution transmission electron microscopy. RESULTS: The highest level of carboplatin was detected in retinas (8.33 ± 1.69 mg/g), up to 24 hours post treatment. The intravitreal concentration continued to increase gradually until 72 hours (3.46 ± 0.26 mg/g). The choroids and lenses showed very low levels of carboplatin after 6 hours, with negligible amounts at 72 hours. No signs of tissue damage were observed on histopathology or electron microscopy. Intravenous concentration of carboplatin was undetectable in all patients. CONCLUSION: Results may indicate an increased facilitated trans-scleral transport of nanoparticle carboplatin, with a sustained-release behavior but without any associated short-term ocular or systemic side effects in humans. The very high concentrations achieved in vitreous and retina after a single posterior subtenon injection may be clinically useful for adjunctive treatment of advanced intraocular retinoblastoma with vitreous seeds. However, further studies are needed to assess long-term toxicity and clinical efficacy.

Polymorphism and nucleotide sequencing of BMPR1B gene in prolific Assam hill goat.

Assam hill goat (Capra hircus) is a prolific local goat in India. bone morphogenetic protein receptor (BMPR1B) gene was studied as a candidate gene for the prolificacy of goats. The objective of the present study was to detect the incidence of mutation in the exonic region of BMPR1B gene of Assam hill goat. Total 90 blood samples were collected randomly from different parts of Assam and genomic DNA were extracted using phenol-chloroform method. The quantity and quality of extracted DNA was examined by spectrophotometry and gel electrophoresis, respectively. PCR amplicon showed a product of 140 bp fragment of BMPR1B gene. The purified product upon digestion with AvaII showed monomorphic banding pattern and revealed wild type alleles with AA genotype. Nucleotide sequencing showed one new mutation 773 (G→C) which is found to be unique in Assam hill goat. Construction of tree at nucleotide level generates from the present experiment lies in common cluster which differs from the other breeds of goat. The analysis of polymorphism for BMPR1B in Assam hill goat indicates that the genetic factor responsible for prolificacy or multiple kidding rates is not related to the reported mutated alleles of BMPR1B gene. Therefore, attempts to be made to detect other SNPs for BMPR1B gene or otherwise effort should be made towards other fecundity gene which might be responsible for the prolificacy of Assam hill goat.

Why extreme dilutions reach non-zero asymptotes: a nanoparticulate hypothesis based on froth flotation.

Extreme dilutions, especially homeopathic remedies of 30c, 200c, and higher potencies, are prepared by a process of serial dilution of 1:100 per step. As a result, dilution factors of 10(60), 10(400), or even greater are achieved. Therefore, both the presence of any active ingredient and the therapeutic efficacy of these medicines have been contentious because the existence of even traces of the starting raw materials in them is inconceivable. However, physicochemical studies of these solutions have unequivocally established the presence of the starting raw materials in nanoparticulate form even in these extreme (super-Avogadro, >10(23)) dilutions. In this article, we propose and validate a hypothesis to explain how nanoparticles are retained even at such enormous dilution levels. We show that once the bulk concentration is below a threshold level of a few nanograms/milliliter (ng/mL), at the end of each dilution step, all of the nanoparticles levitate to the surface and are accommodated as a monolayer at the top. This dominant population at the air-liquid interface is preserved and carried to the subsequent step, thereby forming an asymptotic concentration. Thus, all dilutions are only apparent and not real in terms of the concentrations of the starting raw materials.