A Single Cisterna Magna Injection of AAV Leads to Binaural Transduction in Mice

Viral-mediated gene augmentation, silencing, or editing offers tremendous promise for the treatment of inherited and acquired deafness. Inner-ear gene therapies often require a safe, clinically useable and effective route of administration to target both ears, while avoiding damage to the delicate structures of the inner ear. Here, we examined the possibility of using a cisterna magna injection as a new cochlear local route for initiating binaural transduction by different serotypes of the adeno-associated virus (AAV2/8, AAV2/9, AAV2/Anc80L65). The results were compared with those following canalostomy injection, one of the existing standard inner ear local delivery routes. Our results demonstrated that a single injection of AAVs enables high-efficiency binaural transduction of almost all inner hair cells with a basal-apical pattern and of large numbers of spiral ganglion neurons of the basal portion of the cochlea, without affecting auditory function and cochlear structures. Taken together, these results reveal the potential for using a cisterna magna injection as a local route for binaural gene therapy applications, but extensive testing will be required before translation beyond mouse models.

Immunotherapeutic Peptide Vaccine Approaches to Glioma

Heretofore, there are no FDA-approved immunotherapeutics for malignant gliomas despite many novel therapies currently in different stages of clinical trials. Malignant gliomas are immunosuppressive tumors and are difficult for immune effector cells to infiltrate the tumor sites in the central nervous system. This inefficiency results in median survival of about only two years with a few long-term survivors. Recent clinical trials of vaccine-based immunotherapies against malignant gliomas have demonstrated encouraging results in enhancing progression-free survival and overall survival of patients. The vaccine-based treatments include peptide and heat-shock proteins, dendritic cell-based vaccines, as well as viral-based immunotherapy. In this review, we will focus on recent clinical trials of neoantigen peptide vaccines on gliomas, the delivery routes of such peptide vaccines, their adjuvants, clinical challenges, and its future strategies, respectively.

A Digital Twin for Decision Making on Livestock Feeding

Looking for an accurate and cost-effective solution to measure feed inventories, forecast the feed demand and allow feed suppliers to optimize inventories, production batches, and delivery routes.

IMPROVEMENT OF THE LOGISTIC SERVICE OF RAILWAY FERRY

Purpose. In modern conditions, Ukraine, having an extensive railway network and a developed infrastructure of seaports located on its Black Sea coast, is becoming a link in new goods delivery routes in the direction of the EU-China. Transportation of large consignments of goods in the direction is usually carried out in containers by sea transport. At the same time, such transportation is characterized, on the one hand, by a relatively low cost, and on the other hand, by rather long delivery times. An alternative case is transportation by mixed rail-water communication, which allows, with a moderate increase in cost, to achieve a significant reduction in the delivery time of goods. The economic attractiveness of such a transportation scheme depends significantly on the performance of ferry crossings in the Caspian and Black Seas. In this regard, the purpose of this work is to increase the efficiency of international ferry services by improving its logistics support on coastal ferry complexes. Methodology. To achieve the work purpose, methods of statistical analysis were used to determine the volume and structure of ferry traffic; simulation methods to determine effective options for loading ferries; theory of shunting work to optimize the car classification according to the cargo plan. Results. There were analyzed the requirements for ferry loading and developed a computer model that allows to create acceptable plans for the cars location on ferry decks (cargo plan). On the basis of the obtained variants of the cargo plan, the modeling of the multi-group trains forming by combinatorial and distribution methods has been carried out. Based on the simulation results, recommendations of choosing the effective method for train forming and the required number of cargo plan variants were given. Scientific novelty. The author has improved the method for determining the effective cargo plan of the ferry loading, which takes into account the process of forming the trains of cars to be supplied to the ferry. Practical significance. The obtained results can be used to improve the efficiency of international freight transportation management in mixed rail-water traffic.

Advancement in Ocular Drug Delivery System to Overcome Ocular Barrier

The Ocular drug delivery system (ODDS) is the prominently challenging system faced by pharmaceutical researchers. Ophthalmic preparations are available in buffered, sterile and isotonic solutions. For the ocular delivery of drugs, various types of dosage forms are prepared and dispensed. As the drops are easier for the administration likewise more prescribed dosage form is the eye drop solution. For obtaining prolonged therapeutic effect ointment, suspensions and gelled systems are also used. The presence of various barriers as anatomical, physiological and physiochemical barriers makes difficulties in delivery of drugs in at the intended sites. Scientists invented alternate delivery routes to direct access at intended target sites. Second invention involves development of novel drug delivery systems providing better permeability, treatability and controlled release at target site. The liposomal delivery is beneficial because they have the ability of envelopment and both hydrophobic and hydrophilic drugs are suitable for delivery to both the anterior and posterior segment of the eye. Therefore, the uses of this alternative approach become quite a necessary. This formulation of novel devices will definitely help to the overcome ocular barriers and side effects with conventional topical drops. Current reviews on the conventional formulations of ocular delivery and their advancements followed by current nanotechnology based on the formulation developments. The recent incident with other ocular drug delivery planning consists of in situ gels, implants, contact lens and nano wafers are discussed. Drug delivery at ophthalmic route has been proven significant advancement for the future perspectives.

A brief review on DNA vaccines in the era of COVID-19

This article provides a brief overview of DNA vaccines. First, the basic DNA vaccine design strategies are described, then specific issues related to the industrial production of DNA vaccines are discussed, including the production and purification of DNA products such as plasmid DNA, minicircle DNA, minimalistic, immunologically defined gene expression (MIDGE) and Doggybone™. The use of adjuvants to enhance the immunogenicity of DNA vaccines is then discussed. In addition, different delivery routes and several physical and chemical methods to increase the efficacy of DNA delivery into cells are explained. Recent preclinical and clinical trials of DNA vaccines for COVID-19 are then summarized. Lastly, the advantages and obstacles of DNA vaccines are discussed.

Vaginal Mucoadhesive Drug Delivery System

Mucoadhesive drug delivery systems are delivery systems which utilize the property of bioadhesion of certain polymers which become adhesive on hydration and hence can be used for targeting a drug to a particular region of the body for extended periods of time. Many of these delivery routes, particularly those through the nasal, ocular, reproductive and gastrointestinal system, involve contact with mucosal surfaces. The gastrointestinal route has been particularly popular among medical staff and patients alike. Although convenient, unfortunately, this route can be very inefficient for a number of reasons, including too rapid transit of the drug-containing delivery system past the optimum site for absorption, which is normally the small intestine and to a lesser degree the stomach and colon. Mucoadhesive formulations use polymers as the adhesive component. Mucoadhesive drug delivery systems are available in the form of tablets, films, patches, and gels for oral, buccal, nasal, ocular, vaginal, rectal and topical routes for both systemic and local effects. This review article represents the various aspects of vaginal drug delivery system, bioadhesion mechanism, Theory of bioadhesion, factors affecting bioadhesion, various types of vaginal formulation etc.

Briefbeförderung des Ordens in Livland. Mit vorläufigen statistischen Bewertung

Delivery of Letters in the Teutonic Order in Livonia. With a preliminary statistical analysisThis contribution is on the organization and efficiency of the delivery of letters in the Teutonic Order in Livonia. Firstly, the scarce data on couriers is presented. Main part of the contribution is discussing the phenomenon of registration of time (hour) and place in some of the stations on the delivery routes of letters. This method, used extensively also in Prussia, was most likely introduced in Livonia in the beginning of the 15th century. It was used in case of most urgent letters and was first of all meant to monitor the efficiency of delivery. The majority of the places of registration of time are in the territory of the Order, but there are also some exceptions, when this was done in episcopal castles or manors. High number of letters of the Masters of the Teutonic Order in Tallinn City Archives is also allowing some preliminary statistical analysis, how the space and time was mastered on the route Riga-Wenden-Reval. It appears, that although the letters were ordered to be carried day and night, the calculated average speed is so low, that there were obviously made also some stops for rest on the road.