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Limiting the level of tertiary amines on polyamines leads to biocompatible nucleic acid vectors

Publication date: 30 June 2017 Source:International Journal of Pharmaceutics, Volume 526, Issues 1–2 Author(s): Margarida Isabel Simão Carlos, Kai Zheng, Natalie Garrett, Natrah Arifin, David G. Workman, Ilona Kubajewska, Abdulrahman A. Halwani, Julian Moger, Qi Zhang, Andreas G. Schätzlein, Ijeoma F. Uchegbu We have designed an efficient, synthetic nucleic acid vector, which is relatively non-toxic. [N-(2-ethylamino)-6-O-glycolchitosan – EAGC] polymers were 10–50 fold less toxic than Lipofectamine 2000, able to complex DNA, mRNA and siRNA into positively charged (zeta potential=+40 − 50mV), 50–450nm nanoparticles. The level of tertiary amine N-2-ethylamino substitution (DStert) was inversely proportional to the IC50 of the EAGC polymers in the A431 cell line: IC50=6.18DStert −0.9, r2 =0.9991. EAGC polyplexes were stable against a heparin challenge, able to protect the nucleic acids from nuclease degradation and achieve levels of transfection comparable to Lipofectamine 2000 formulations. The relative biocompatibility of the vector allowed 10 fold higher doses of DNA (1μg compared to 0.1μg per well with Lipofectamine 2000) and siRNA (10.7μg per well vs 1.3μg with Lipofectamine 2000) to be applied to cells, when compared to Lipofectamine 2000. Finally intranasal application of EAGC – siRNA complexes resulted in siRNA transfer to the neurons of the olfactory bulb. Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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Authors: Yu HX, Han CS, Xue JR, Han ZF, Xin H Abstract INTRODUCTION: Esophageal hiatal hernia involves abnormal abdominal entry into thoracic cavity. It is classified based on orientation between esophageal junction and diaphragm. Sliding hiatal hernia (Type-I) comprises the most frequent category, emanating from right crus of diaphragm. Type-II esophageal hernia engages both left and right muscular crura. Type-III and IV additionally include the left crus. Age and increased body mass index are key risk factors, and congenital skeletal aberrations trigger pathogenesis through intestinal malrotations. Familiar manif...
Source: Expert Review of Gastroenterology and Hepatology - Category: Gastroenterology Tags: Expert Rev Gastroenterol Hepatol Source Type: research
[Prospective, monocentric, uncontrolled study of efficacy, tolerance and adherence of cyclosporin 0.1 % for severe dry eye syndrome]. J Fr Ophtalmol. 2018 Feb 12;: Authors: Boujnah Y, Mouchel R, El-Chehab H, Dot C, Burillon C, Kocaba V Abstract PURPOSE: To evaluate the efficacy, tolerability and treatment adherence of Ikervis® (Santen, SAS) (ciclosporine 0.1 %) for first line therapy or following treatment with Restasis® (Allergan, Inc.) (ciclosporine 0.05 %) for severe dry eye syndrome. MATERIAL AND METHODS: A prospective, monocentric, uncontrolled study was conducted betwee...
Source: Journal Francais d Ophtalmologie - Category: Opthalmology Tags: J Fr Ophtalmol Source Type: research
CONCLUSION: Early diagnosis and strict control of inflammatory activity have led to a dramatic reduction in the incidence of vision-threatening secondary complications. In the majority of cases, it has also been possible to resolve cystoid macular edema, which, if insufficiently controlled by systemic therapy, usually responds well to intravitreal dexamethasone implants. PMID: 29452454 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Brandl C, Weber BHF Abstract Today, the search for therapeutic options to treat retinal degeneration often relies on an in-depth understanding of the underlying pathological events. Alternatively, it is conceivable to search, in an undirected screening approach, for chemical compounds affecting disease outcome. For both approaches, there is an urgent need for in vitro and, ideally, in vivo disease models that adequately reflect the site of pathology. Currently available animal models possess limitations as they often develop only defined aspects of disease. Primary cell cultures, derived from the posterior...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Schmidt S, Hubich S, Vetter JM, Wirbelauer C Abstract BACKGROUND: Torsional mode phacoemulsification results in more effective fragmentation of the nucleus due to a different movement of the phacotip. In this clinical study, we investigated the influence of a modified tip design and active fluidics on the efficacy of phacoemulsification and safety for the corneal endothelium. MATERIAL AND METHODS: We conducted a prospective randomized 2 : 1 study in which 40 patients were operated on with the mini-flared Kelman Tip using the Infiniti® System (group 1), and 20 patients were operated on...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Wipf M, Bok-Beaube C, Palmowski-Wolfe A Abstract Cyclic strabismus is a rare disease of unknown origin. If untreated, it leads to manifest strabismus with the risk of amblyopia in children. Treatment is generally surgical. Here we report on three children in whom cyclic esotropia was successfully treated with one bimedial injection of 5 IU Botox®. All patients remained orthotropic with good stereo functions at the last follow-ups at 16, 11, and 8 months. Botulinum toxin offered a minimally invasive treatment option in these patients. PMID: 29452451 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
CONCLUSIONS: In summary, the short-term cost-cost comparison demonstrates that steroid implants can provide significant cost savings versus in-label anti-VEGF treatment for center-involving diabetic macular edema. Single application of the long-lasting Fluocinolone acetonide implant is the most cost-efficient in-label treatment option. PMID: 29452450 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Roemer S, Bissig A, Rocca A, Du Pasquier R, Guex-Crosier Y PMID: 29452449 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Reinshagen H, Gerding H PMID: 29452448 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Nordqvist C, Fracheboud S, Guex-Crosier Y PMID: 29452447 [PubMed - as supplied by publisher]
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
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