Poly(Glycerol Adipate-co-ω-Pentadecalactone) Spray-Dried Microparticles as Sustained Release Carriers for Pulmonary Delivery

Purpose The aim of this work was to optimize biodegradable polyester poly(glycerol adipate-co-ω-pentadecalactone), PGA-co-PDL, microparticles as sustained release (SR) carriers for pulmonary drug delivery. Methods Microparticles were produced by spray drying directly from double emulsion with and without dispersibility enhancers ( L -arginine and L -leucine) (0.5–1.5%w/w) using sodium fluorescein (SF) as a model hydrophilic drug. Results Spray-dried microparticles without dispersibility enhancers exhibited aggregated powders leading to low fine particle fraction (%FPF) (28.79 ± 3.24), fine particle dose (FPD) (14.42 ± 1.57 μg), with a mass median aerodynamic diameter (MMAD) 2.86 ± 0.24 μm. However, L -leucine was significantly superior in enhancing the aerosolization performance ( L- arginine:%FPF 27.61 ± 4.49–26.57 ± 1.85; FPD 12.40 ± 0.99–19.54 ± 0.16 μg and MMAD 2.18 ± 0.35–2.98 ± 0.25 μm, L -leucine:%FPF 36.90 ± 3.6–43.38 ± 5.6; FPD 18.66 ± 2.90–21.58 ± 2.46 μg and MMAD 2.55 ± 0.03–3.68 ± 0.12 μm). Incorporating L -leucine (1.5%w/w) reduced the burst release (24.04 ± 3.87%) of SF compared to unmodified formulations (41.87 ± 2.46%), with both undergoing a square root of time (Higuchi’s pattern) dependent release. Comparing the toxicity profiles of PGA-co-PDL with L -leucine (1.5%w/w) (5 mg/ml) and poly(lactide-co-glycolide), (5 mg/ml) spray-dried microparticles in human bronchial epithelial 16HBE14o- cell lines, resulted in cell viability of 85.57 ± 5.44 and 60.66 ± 6.75%, respectively, after 72 h treatment. Conclusion The above data suggest that PGA-co-PDL may be a useful polymer for preparing SR microparticle carriers, together with dispersibility enhancers, for pulmonary delivery

Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

<p>Abstract</p> <p>Background</p> <p>Global transcriptional analysis of loblolly pine (<it>Pinus taeda </it>L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine.</p> <p>Results</p> <p>Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10^-30) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function.</p> <p>Conclusion</p> <p>PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the genes identified are known to be up-regulated in response to osmotic stress in pine and other plant species and encode proteins involved in both signal transduction and stress tolerance. Gene expression levels returned to control values within a 48-hour recovery period in all but 76 transcripts. Correlation network analysis indicates a scale-free network topology for the pine root transcriptome and identifies central nodes that may serve as drivers of drought-responsive transcriptome dynamics in the roots of loblolly pine.</p

Use of Kidneys with Small Renal Tumors for Transplantation

Population of patients with end-stage renal disease increases every day. There is a vast difference in the number of patients on the waiting list for a kidney transplant, and the number of donors and the gap increases every year. The use of more marginal organs can increase the donor pool. These organs include the kidneys with small renal cell carcinomas (RCTC). There has been a number of reports in the literature about the use of these grafts for renal transplant after tumor excision and reconstruction. These grafts have been reported to be used with good renal function outcomes without an increased risk for malignancy recurrences. We present the collection of evidence for the use of kidneys with RCC for transplantation, technique used for surgical resection, and reconstruction as well as insights on the recommendations for the use of these grafts

The Effect of Engineered Mannitol-Lactose Mixture on Dry Powder Inhaler Performance

Purpose To co-crystallise mannitol and lactose with a view to obtaining crystals with more favourable morphological features than either lactose or mannitol alone, suitable for use as carriers in formulations for dry powder inhalers (DPIs) using simultaneous engineering of lactose-mannitol mixtures. Methods Mannitol and lactose individually and the two sugars with three different ratios were crystallised/co-crystallised using anti-solvent precipitation technique. Obtained crystals were sieved to separate 63–90 μm size fractions and then characterised by size, shape, density and in vitro aerosolisation performance. Solid state of crystallized samples was studied using FT-IR, XRPD and DSC. Results At unequal ratios of mannitol to lactose, the elongated shape dominated in the crystallisation process. However, lactose exerted an opposite effect to that of mannitol by reducing elongation ratio and increasing the crystals’ width and thickness. Crystallised β-lactose showed different anomers compared to commercial lactose (α-lactose monohydrate). Crystallised α-mannitol showed different polymorphic form compared to commercial mannitol (β-mannitol). Crystallised mannitol:lactose showed up to 5 transitions corresponding to α-mannitol, α-lactose monohydrate, β-lactose, 5α-/3β-lactose and 4α-/1β-lactose. In vitro deposition assessments showed that crystallised carriers produced more efficient delivery of salbutamol sulphate compared to formulations containing commercial grade carriers. Conclusion The simultaneous crystallization of lactose-mannitol can be used as a new approach to improve the performance of DPI formulations