Polymeric Micelles in Ocular Drug Delivery: Rationale, Strategies and Challenges

Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim here is to review the aqueous-based formulation of drug loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. These innovative nanosystems can provide the biopharmaceutical advantages of higher permeation and enhancement of residence time at ocular surface for better drug absorption through ocular barriers. Mucoadhesive properties of biopolymers forming micelle enhance their contact time and minimize their elimination from the absorbing surface, consequently increasing the bioavailability of the drug. Their physicochemical characteristics are also important with respect to the industrial production and patient compliance. Drug loaded polymeric micelles can be fabricated by simple and cost effective techniques with improved physical stability which fulfils the requirements for industrial acceptance. Innovative polymeric micelle formulations allow their easy application in the form of eye drops without blurring of vision and discomfort, thus achieving patient compliance requirements

Early detection of sepsis using artificial intelligence : a scoping review protocol

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. To decrease the high case fatality rates and morbidity for sepsis and septic shock, there is a need to increase the accuracy of early detection of suspected sepsis in prehospital and emergency department settings. This may be achieved by developing risk prediction decision support systems based on artificial intelligence. Methods: The overall aim of this scoping review is to summarize the literature on existing methods for early detection of sepsis using artificial intelligence. The review will be performed using the framework formulated by Arksey and O’Malley and further developed by Levac and colleagues. To identify primary studies and reviews that are suitable to answer our research questions, a comprehensive literature collection will be compiled by searching several sources. Constrictions regarding time and language will have to be implemented. Therefore, only studies published between 1 January 1990 and 31 December 2020 will be taken into consideration, and foreign language publications will not be considered, i.e., only papers with full text in English will be included. Databases/web search engines that will be used are PubMed, Web of Science Platform, Scopus, IEEE Xplore, Google Scholar, Cochrane Library, and ACM Digital Library. Furthermore, clinical studies that have completed patient recruitment and reported results found in the database ClinicalTrials.gov will be considered. The term artificial intelligence is viewed broadly, and a wide range of machine learning and mathematical models suitable as base for decision support will be evaluated. Two members of the team will test the framework on a sample of included studies to ensure that the coding framework is suitable and can be consistently applied. Analysis of collected data will provide a descriptive summary and thematic analysis. The reported results will convey knowledge about the state of current research and innovation for using artificial intelligence to detect sepsis in early phases of the medical care chain. Ethics and dissemination: The methodology used here is based on the use of publicly available information and does not need ethical approval. It aims at aiding further research towards digital solutions for disease detection and health innovation. Results will be extracted into a review report for submission to a peer-reviewed scientific journal. Results will be shared with relevant local and national authorities and disseminated in additional appropriate formats such as conferences, lectures, and press releases.

Polymers in Ophthalmology

El articulo Polymers in ophthalmology es parte del capitulo 6 del libro Advanced polymers in medicine.Ophthalmological sciences are disciplines focused in the health of the eyes and related structures, as well as vision, visual systems, and vision information processing in humans; dealing with the anatomy, physiology and diseases of the eye. Along time a wide variety of materials, including metals, ceramics and polymers, have been developed and used in different ophthalmic applications. Although, modern ophthalmic devices and drug platforms are made with polymeric materials. Applications of polymers in ophthalmology include vitreous replacement fluids, contact lenses, intraocular lenses, artificial orbital walls, artificial corneas, artificial lacrimal ducts, glaucoma drainage devices, viscoelastic replacements, drug delivery systems, sclera buckles, retinal tacks and adhesives, and ocular endotamponades. Both synthetic and natural polymeric biomaterials are used in ophthalmological applications, although in the lasts years most efforts were focused in natural and biocompatible materials, such as gelatin, hyaluronan, chitosan, gums, etc.; developing, tablets, films, suspensions, nanosystems, inserts, etc. This chapter attempts to offers an insight into the importance of polymers in the design and development of pharmaceuticals platforms used in ocular therapeutics.Fil: Calles, Javier Adrián. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; Argentina.Fil: Bermudez, José María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones para la Industria Química; Argentina.Fil: Bermudez, José María. Universidad Nacional de Salta. Facultad de Ingeniería. Instituto de Investigaciones para la Industria Química; Argentina.Fil: Valles, Enrique Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Bahía Blanca; Argentina.Fil: Valles, Enrique Marcelo. Universidad Nacional del Sur. Planta Piloto de Ingeniería Química; ArgentinaFil: Allemandi, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina.Fil: Allemandi, Daniel Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Fil: Palma, Santiago Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; Argentina.Fil: Palma, Santiago Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Unidad de Investigación y Desarrollo en Tecnología Farmacéutica; Argentina.Otras Ciencias Química

Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial

Background: Risdiplam is an oral small molecule approved for the treatment of patients with spinal muscular atrophy, with approval for use in patients with type 2 and type 3 spinal muscular atrophy granted on the basis of unpublished data. The drug modifies pre-mRNA splicing of the SMN2 gene to increase production of functional SMN. We aimed to investigate the safety and efficacy of risdiplam in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. Methods: In this phase 3, randomised, double-blind, placebo-controlled study, patients aged 2–25 years with confirmed 5q autosomal recessive type 2 or type 3 spinal muscular atrophy were recruited from 42 hospitals in 14 countries across Europe, North America, South America, and Asia. Participants were eligible if they were non-ambulant, could sit independently, and had a score of at least 2 in entry item A of the Revised Upper Limb Module. Patients were stratified by age and randomly assigned (2:1) to receive either daily oral risdiplam, at a dose of 5·00 mg (for individuals weighing ≥20 kg) or 0·25 mg/kg (for individuals weighing <20 kg), or daily oral placebo (matched to risdiplam in colour and taste). Randomisation was conducted by permutated block randomisation with a computerised system run by an external party. Patients, investigators, and all individuals in direct contact with patients were masked to treatment assignment. The primary endpoint was the change from baseline in the 32-item Motor Function Measure total score at month 12. All individuals who were randomly assigned to risdiplam or placebo, and who did not meet the prespecified missing item criteria for exclusion, were included in the primary efficacy analysis. Individuals who received at least one dose of risdiplam or placebo were included in the safety analysis. SUNFISH is registered with ClinicalTrials.gov, NCT02908685. Recruitment is closed; the study is ongoing. Findings: Between Oct 9, 2017, and Sept 4, 2018, 180 patients were randomly assigned to receive risdiplam (n=120) or placebo (n=60). For analysis of the primary endpoint, 115 patients from the risdiplam group and 59 patients from the placebo group were included. At month 12, the least squares mean change from baseline in 32-item Motor Function Measure was 1·36 (95% CI 0·61 to 2·11) in the risdiplam group and –0·19 (–1·22 to 0·84) in the placebo group, with a treatment difference of 1·55 (0·30 to 2·81, p=0·016) in favour of risdiplam. 120 patients who received risdiplam and 60 who received placebo were included in safety analyses. Adverse events that were reported in at least 5% more patients who received risdiplam than those who received placebo were pyrexia (25 [21%] of 120 patients who received risdiplam vs ten [17%] of 60 patients who received placebo), diarrhoea (20 [17%] vs five [8%]), rash (20 [17%] vs one [2%]), mouth and aphthous ulcers (eight [7%] vs 0), urinary tract infection (eight [7%] vs 0), and arthralgias (six [5%] vs 0). The incidence of serious adverse events was similar between treatment groups (24 [20%] of 120 patients in the risdiplam group; 11 [18%] of 60 patients in the placebo group), with the exception of pneumonia (nine [8%] in the risdiplam group; one [2%] in the placebo group). Interpretation: Risdiplam resulted in a significant improvement in motor function compared with placebo in patients aged 2–25 years with type 2 or non-ambulant type 3 spinal muscular atrophy. Our exploratory subgroup analyses showed that motor function was generally improved in younger individuals and stabilised in older individuals, which requires confirmation in further studies. SUNFISH part 2 is ongoing and will provide additional evidence regarding the long-term safety and efficacy of risdiplam. Funding: F Hoffmann-La Roche