Bioreducible polyethylenimine core-shell nanostructures as efficient and non-toxic gene and drug delivery vectors.

Low molecular weight branched polyethylenimine (LMW bPEIs 1.8 kDa) have received considerable attention for the fabrication of nucleic acid carriers due to their biocompatible and non-toxic nature. However, due to the inadequate nucleic acid complexation ability and transportation across the cell membrane, these show poor transfection efficacy, limiting their clinical applications. Therefore, to overcome these challenges, in this study, we have grafted bPEI 1.8 kDa with a disulfide bond containing hydrophobic moiety, 3-(2-pyridyldithio) propionic acid (PDPA), via amide linkages through EDC/NHS-mediated coupling to obtain N-[3-(2-pyridyldithio)] propionoyl polyethylenimine (PDPP) conjugates. The best formulation for nucleic acid transfection was evaluated after preparing a series of PDPP conjugates by varying the amount of PDPA. In an aqueous environment, these PDPP conjugates self-assembled to form spherical shaped core-shell PDPP nanostructures with size ranging from âˆ¼188-307 nm and zeta-potential from ∼ +3 to +19 mV. The positively charged surface of the core-shell nanocomposites helps in the binding of plasmid DNA (pDNA), its transportation inside the cell, and protection against enzymes. Evaluation of PDPP/pDNA complexes on mammalian cells revealed that all these complexes showed significantly improved transfection efficacy without hampering cytocompatibility. Amongst all, the pDNA complex of PDPP-2 exhibited the best transfection efficiency (i.e. >6-fold) in comparison to pDNA complex of the native bPEI. The nanocomposites exhibited the redox responsive behavior advantageous for therapeutic delivery to the tumor cells. The core of the nanostructures facilitate the encapsulation of a hydrophobic model drug, ornidazole. In vitro drug release analysis showed a faster release rate in response to a reductant mimicking the cellular environment. Altogether, these nanostructures have great potential to co-deliver both drug and gene simultaneously in response to tumor cell reductive microenvironment in vitro and could be used as the next-generation delivery system.

Radiotherapy treatment of human inflammatory diseases and conditions: Optimal dose.

During the early part of the past century, hundreds of clinical studies involving more than 37,000 patients were conducted that showed radiotherapy (RT) to be a successful and safe alternative to drug therapy for the treatment of many diverse inflammatory conditions and diseases (e.g. tendonitis, bursitis, arthritis, and serious inflammatory lung conditions). Data from these studies were collected and analyzed with the intent of estimating an optimal dosing range for RT that would induce an efficacious treatment response. RT was reported to be frequently effective after only a single treatment, with a rapid (within 24 h) and often long-lasting (from months to years) relief from symptoms. Over a two-decade span from the 1920s to the 1940s, the therapeutic responses to a single RT treatment consistently improved as the dosing for multiple ailments decreased over time to between 30 roentgen (r) and 100 r. These findings are significant and in agreement with a number of contemporary reports from Germany where RT has been commonly and successfully employed in treating ailments with an inflammatory origin. A proposed mechanism by which RT mitigates inflammation and facilitates healing is via the polarization of macrophages to an anti-inflammatory or M2 phenotype.

Historical use of x-rays: treatment of inner ear infections and prevention of deafness.

PURPOSE: This article provides an historical assessment of the role of radiotherapy in the treatment of inner ear infections. MATERIALS AND METHODS: The research utilized a literature-based evaluation of the use of x-rays during the first half of the 20th century on the treatment of otitis media (OM), mastoiditis, and cervical adenitis and their impact on the occurrence of deafness. RESULTS: X-Rays were consistently found to be effective as a treatment modality at relatively low doses, in the range of 10-20% of the skin erythema dose, rapidly reducing inflammation, and accelerating the healing process. The mechanistic basis of the clinical successes, while addressed by contemporary researchers, is evaluated in the present article in light of current molecular biology advances, which indicate that clinically effective low doses of ionizing radiation act via the creation of an anti-inflammatory phenotype in highly inflamed tissue. CONCLUSIONS: X-Ray treatment of OM, mastoiditis, and cervical adenitis was widely accepted in the first half of the 20th century by clinicians as an effective treatment when administered within an appropriate dosage range.

Polyamine-assisted rapid and clean cleavage of oligonucleotides from cis-diol bearing universal support.

Polyamine-assisted deprotection conditions have been developed for the rapid and clean cleavage of oligonucleotide chains from a cis-diol group bearing universal polymer support, making it compatible with modern oligonucleotide synthesis via all types of phosphoramidite synthons, including base labile protecting group bearing synthons as well. The synthesized oligonucleotides were found to be comparable with the corresponding standard oligomers with respect to their retention time on HPLC, mass on MALDI-TOF and biological activity in PCR amplification.