Opportunities and Challenges in the Delivery of mRNA-based Vaccines

In the past few years, there has been increasing focus on the use of messenger RNA (mRNA) as a new therapeutic modality. Current clinical efforts encompassing mRNA-based drugs are directed toward infectious disease vaccines, cancer immunotherapies, therapeutic protein replacement therapies, and treatment of genetic diseases. However, challenges that impede the successful translation of these molecules into drugs are that (i) mRNA is a very large molecule, (ii) it is intrinsically unstable and prone to degradation by nucleases, and (iii) it activates the immune system. Although some of these challenges have been partially solved by means of chemical modification of the mRNA, intracellular delivery of mRNA still represents a major hurdle. The clinical translation of mRNA-based therapeutics requires delivery technologies that can ensure stabilization of mRNA under physiological conditions. Here, we (i) review opportunities and challenges in the delivery of mRNA-based therapeutics with a focus on non-viral delivery systems, (ii) present the clinical status of mRNA vaccines, and (iii) highlight perspectives on the future of this promising new type of medicine

Simultaneous quantification of multiple RNA cargos co-loaded into nanoparticle-based delivery systems

Robust, sensitive, and versatile analytical methods are essential for quantification of RNA drug cargos loaded into nanoparticle-based delivery systems. However, simultaneous quantification of multiple RNA cargos co-loaded into nanoparticles remains a challenge. Here, we developed and validated the use of ion-pair reversed-phase high-performance liquid chromatography combined with UV detection (IP-RP-HPLC-UV) for simultaneous quantification of single- and double-stranded RNA cargos. Complete extraction of RNA cargo from the nanoparticle carrier was achieved using a phenol:chloroform:isoamyl alcohol mixture. Separations were performed using either a C18 or a PLRP-S column, eluted with 0.1 M triethylammonium acetate (TEAA) solution as ion-pairing reagent (eluent A), and 0.1 M TEAA containing 25 % (v/v) CH3CN as eluent B. These methods were applied to quantify mRNA and polyinosinic:polycytidylic acid co-loaded into lipid-polymer hybrid nanoparticles, and single-stranded oligodeoxynucleotide donors and Alt-R CRISPR single guide RNAs co-loaded into lipid nanoparticles. The developed methods were sensitive (limit of RNA quantification 0.997), and accurate (≈ 100 % recovery of RNA spiked in nanoparticles). Hence, the present study may facilitate convenient quantification of multiple RNA cargos co-loaded into nanoparticle-based delivery systems

Characterization of Al2O3 reinforced Al 6061 metal matrix composite

Composites are a class of materials that give the desired individual tribological and mechanical characteristics. In composite materials, more than two materials are combined to provide a unique combination of properties. This article describes the tribological and mechanical properties of Al6061 reinforced with Al2O3, found experimentally. This article describes the preparation of Al6061 composites with 5 % Al2O3 (size 50 microns) by stir casting process. The hardness of Al6061 with and without amplification was found out with the help of Rockwell hardness tester for 10 seconds at a load of 100 kg. It was found that the hardness of Al2O3 reinforced Al6061 increases compared to unreinforced Al6061. The characteristics related to wear of Al6061 and the new composite material Al6061+Al2O3 were studied. The “pin on disk” method was used with the variation of load varying from 5N-200N and a speed range of 200-1500. An analysis of the sensitivity of key parameters such as load and speed is also described. The results show that the newly developed composite material has a lesser specific rate of wear

Graphene family nanomaterials as emerging sole layered nanomaterials for wastewater treatment: Recent developments, potential hazards, prevention and future prospects

Layered carbon nanomaterials (LCNs) are interesting topic of research owing to their compelling applications in diverse fields, simple preparation methods, and several exciting traits. In LCNs, graphene family nanomaterials (GFNs) i.e. graphene, graphene oxide (GO), and reduced graphene oxide (rGO) are highly exploited in recent years due to their planer morphology rendering extraordinarily high surface area (∼2600m2/g), amphiphilic nature, tunable optical and electrical properties, and rich surface oxy-functionalities (as in GO). Owing to these factors, GFNs have been emerged as the sole multifunctional layered nanomaterial with high potential of tailoring its properties through simple doping (n or p-type) and replacing metal based nanomaterials for various catalytic and adsorption-based environmental remediation strategies. In order to summarize the latest advancements, applications, potential benefits, risks, assessment of limitations, and challenges related to these materials, a well-crafted comprehensive review article is very valuable resource for researchers, and policymakers working towards environmental sustainability. Additionally, a review article on layered carbon nanomaterials for environmental applications is significant to bridge the gap between academia and industry by shedding light on the scalability, cost-effectiveness, and commercial viability of LCNs, facilitating their translation from the laboratory to real-world applications. The presented review article thoroughly discusses the morphological, structural, and chemical features of GFNs which enables them to adsorb both cationic and anionic organic contaminants in superlative manners. Additionally, several emerging applications of such GFNs as a sole nanomaterials in form of excellent adsorbents (for various species), photocatalysts, antibacterial agents, and as sensing materials mainly in water treatment are thoroughly discussed. In addition to this, the presented review also articulates a potential hazard associated with the subsequent recovery process of the employed dye/chemical adsorbed GFNs during adsorption or photodegradation processes. The current review summarizes all such recent efforts of environmental remediation using sole GFNs in details. Apart from that, the review article also suggests the future trends exploring the wide range of types and applications of these materials

Peripheral neurectomy in treatment of trigeminal neuralgia: A case report

Neuropathic pain is nonadaptive and does not contribute to healing, such as would be the case with pain attributable to tissue inflammation, where pain results in adaptive behaviors, such as use limitation, guarding, rest, and avoidance, which contribute to healing. Trigeminal neuralgia is a debilitating, lancinating, and excruciating orofacial pain illness. Tic douloureux is the other popular name of trigeminal neuralgia because of the facial expression accompanying the episodic pain. Here we report a case of trigeminal neuralgia of infraorbital and greater palatine nerve in a 54-year-old female patient. Peripheral neurectomy was done under local anesthesia as the treatment

Sky Cargo: Self-Navigating Delivery Drone

<p>The rapid growth of e-commerce and the increasing demand for efficient, sustainable, reliable, economical delivery solutions have driven the development of autonomous delivery drones. The "Sky  Cargo Self-Navigating Delivery Drone," has a cutting- edge technology designed to revolutionize the logistics  and transportation industry. The system has a predefined path between its starting point to its delivery location based. The system ensures the precision landing at the receiver end by verification at the delivery location by the uniquely generated Aruco marker. An optimal path is given to the drone by performing the mathematical calculations between the starting point to its delivery point</p><p>Keywords:- Autonomous drone, Self-Navigating, precision landing, Aruco marker, optimal path.</p&gt

Identification of Factors of Importance for Spray Drying of Small Interfering RNA-Loaded Lipidoid-Polymer Hybrid Nanoparticles for Inhalation

Background With the recent approval of the first small interfering RNA (siRNA) therapeutic formulated as nanoparticles, there is increased incentive for establishing the factors of importance for the design of stable solid dosage forms of such complex nanomedicines. Methods The aims of this study were: (i) to identify factors of importance for the design of spray-dried siRNA-loaded lipidoid-poly(DL-lactic-co-glycolic acid) hybrid nanoparticles (LPNs), and (ii) to evaluate their influence on the resulting powders by using a quality-by-design approach. Critical formulation and process parameters were linked to critical quality attributes (CQAs) using design of experiments, and an optimal operating space (OOS) was identified. Results A series of CQAs were identified based on the quality target product profile. The loading (ratio of LPNs to the total solid content) and the feedstock concentration were determined as critical parameters, which were optimized systematically. Mannitol was chosen as stabilizing excipient due to the low water content of the resulting powders. The loading negatively affected the colloidal stability of the LPNs, whereas feedstock concentration correlated positively with the powder particle size. The optimal mannitol-based solid formulation, defined from the OOS, displayed a loading of 5% (w/w), mass median aerodynamic diameter of 3.3 +/- 0.2 mu m, yield of 60.6 +/- 6.6%, and a size ratio of 1.15 +/- 0.03. Dispersed micro-embedded LPNs had preserved physicochemical characteristics as well as in vitro siRNA release profile and gene silencing, as compared to non-spray-dried LPNs. Conclusion The optimal solid dosage forms represent robust formulations suitable for higher scale-up manufacturing