Route Of Delivery Research Articles

Nanocellulose-alginate composite beads for improving Ciprofloxacin bioavailability

Nanocellulose is a potential material utilized in numerous biomedical applications. However, its hydrophilic characteristic and uncontrolled encapsulated drug release hinders nanocellulose uses in oral drug administration. Thus, this work developed novel nanocellulose/alginate composite (CNC/Alg) beads for oral delivery and bioavailability enhancement of a model drug, Ciprofloxacin (CIP). CNC was green synthesized employing electrolysis process from sugarcane bagasse. CNC/Alg beads were formulated by dropwise adding CNC-Alg mixture in CaCl2 solution at room temperature. CIP was incorporated into CNC/Alg beads by adsorption technique. X-ray diffractometry and Fourier-transform infrared spectra images showed that the beads were effectively produced with high crystallinity of 75.5 %, and the typical bond of cellulose and alginate. Within 4 h of adsorption, CIP loading efficiency reached 45.27 %, with 87.2 % molecules in the zwitterionic state. The adsorption followed Elovich and pseudo-second-order models, indicating a multi-mechanism including both physical and chemical adsorptions. Importantly, in gastrointestinal tract, the beads could protect CIP from acidic stomach environment while releasing it sustainably in simulated intestinal condition (75.05 %). The beads also showed strong antibacterial activity against both Gram(−) and Gram(+) bacteria, as evidenced by low IC50 and minimum inhibitory concentration values. Finally, CNC/Alg beads could improve CIP bioavailability for effective oral drug delivery route.

Review on electrospray nanoparticles for drug delivery: Exploring applications

AbstractElectrospraying has emerged as a versatile technique in the pharmaceutical field due to its potential in drug delivery and formulation. With its advantages of cost‐effectiveness, reproducibility, ease of operation, and scalability, electrospraying offers numerous benefits for pharmaceutical applications. Notably, the production of nanoparticles using electrospraying provides unique properties, including small size, drug encapsulation capabilities, biocompatibility, and scalability. Electrospray nanoparticles have demonstrated significant promise in various drug delivery routes, such as oral and topical administration. These nanoparticles enhance drug stability, protection, and permeability, effectively overcoming limitations associated with these routes. Moreover, electrospray nanoparticles have proven valuable in targeted drug delivery, improving drug bioavailability and efficacy. Their ability to penetrate tissues and cells enables enhanced drug delivery to specific sites within the body. Additionally, electrospray nanoparticles can be tailored with targeting ligands or responsive components for controlled release and combination therapy, exhibiting successful applications in cancer treatment and neurological disorders. Therefore, electrospray nanoparticle technology shows great promise in biomedical applications, offering a versatile platform for targeted drug delivery and therapeutic interventions. This comprehensive review examines the various drug delivery applications of electrospraying and provides insights into its possibilities and challenges. The paper discusses the principles, methods, and parameters of electrospraying, while also exploring its use in fabricating drug delivery systems, addressing poorly soluble drugs. By synthesizing the findings from multiple studies, this review offers a comprehensive understanding of electrospraying's current state and potential in the pharmaceutical industry.

Exploring Nasal Anatomical Peculiarities: Illuminating Nasyakarma as a Paradigm Shift in Addressing Central Nervous System Disorders

Abstract: The nasal route holds a special place in Ayurveda, particularly in the practice of Nasya karma. The nose, regarded as an opening to the "shiras" or head, possesses anatomical peculiarities that make it an ideal route for drug administration. The developmental origins of the nose lie in neural crest cells, which migrate during gestation, forming the nasal placodes and giving rise to the intricate nasal structure. Within the diverse approaches to drug delivery,nasya karma emerges as a promising carrier for brain-targeted therapeutics. This comprehensive review bridges modern pharmaceutical advancements with ancient Ayurvedic wisdom, emphasizing the significance of the nose as a crucial route for drug delivery and its potential role in treating central nervous system disorders.

Online optimal scheduling for battery swapping charging systems with partial delivery

Battery swapping–charging system (BSCS) is a promising operating paradigm to provide centering charging and battery swapping service for electric vehicles in transportation electrification. Facing real-time information on battery demand under the limited transporting trucks, flexible online optimization of battery delivery and transportation routing is essential for meeting practical requirements. This paper investigates the real-time scheduling problem in BSCS, considering the battery partial delivery, energy demand, delivery deadline, and vehicle routing. Considering the non-deterministic polynomia hardness of battery transportation, the offline BSCS is a time-consuming task and is unsuitable for the online setting. A Lagrangian relaxation-based Benders decomposition is proposed for parallel and real-time implementation, improving the scheduling efficiency. To tackle future information such as battery demands and delivery deadlines, by introducing the dummy copy, the offline algorithm is embedded within a rolling horizon framework to solve in real-time repeatedly. Finally, case studies using real road maps in Shanghai and Belgium have verified the validity of the proposed online framework and confirmed the necessity of considering partial delivery in enhancing the operation flexibility of BSCS. The computational efficiency of the proposed algorithm is studied under different scales of the road network, and the profit from partial delivery and online implementation are highlighted.

Comparison of the effects of intranasal and intramuscular midazolam–butorphanol–ketamine on intraocular pressure, tear production and sedation in New Zealand White rabbits

ObjectiveTo compare the effects of intranasal (IN) and intramuscular (IM) midazolam–butorphanol–ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits. Study designProspective, randomized, crossover experimental study. AnimalsFourteen male New Zealand White rabbits, aged 1–2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation). MethodsRabbits were administered midazolam (1 mg kg–1), butorphanol (1.5 mg kg–1) and ketamine (5 mg kg–1) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (fR), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO2) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded. ResultsDrug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), fR (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points. Conclusions and clinical relevanceThe combination of midazolam–butorphanol–ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration.

Maternal and Neonatal Outcomes with One Abnormal Value on 100g Three Hour Glucose Tolerance Test in Pregnancy

Purpose: The primary objective of this study was to compare pregnancy outcomes for patients with no elevated glucose values, one elevated glucose value, and 2 or more elevated glucose values on the 3-hour glucose tolerance test (GTT). Methods: This was a retrospective chart review of obstetric patients seen by residents and attending physicians at a single institution from 2015 to 2020 who were required to complete a 3-hour glucose tolerance test (GTT). Data extracted from the maternal chart included demographic information, BMI, route of delivery, presence of preeclampsia, chorioamnionitis, shoulder dystocia and preterm labor. Data extracted from the neonatal chart included blood glucose level after birth, birth weight, Apgar scores, and if NICU admission was required. Continuous data were analyzed using one-way ANOVA to compare the 3 groups, followed by post-hoc Tukey HSD to compare the 1 abnormal value group to the control group. Dichotomous data were analyzed using Chi square tests. Logistic regression was performed using shoulder dystocia as the outcome. Results: Patients with two or more elevated GTT values had higher age and BMI and were more likely to be prescribed diabetic medications compared to those with normal or one elevated value. They were also more likely to deliver at an earlier gestational age. Patients with one elevated GTT value experienced a statistically significant higher chance of shoulder dystocia compared to patients with all normal GTT results (OR 2.34; 95% CI 1.05, 5.20). Patients with two or more elevated values were more likely to have preeclampsia and a neonate requiring NICU admission. There were no differences in cesarean delivery rate, hemorrhage or chorioamnionitis between the groups. Conclusions: Patients with one elevated GTT value are a special subset of patients who do not meet criteria for gestational diabetes, yet do not have normal glucose testing results. We hypothesize that this group is at higher risk of shoulder dystocia because these patients may have hyperglycemia but often do not receive the same type of monitoring, dietary education, medication initiation and induction timing as patients who meet criteria for gestational diabetes.

Improving Outcomes After Post–Cardiac Arrest Brain Injury: A Scientific Statement From the International Liaison Committee on Resuscitation

This scientific statement presents a conceptual framework for the pathophysiology of post–cardiac arrest brain injury, explores reasons for previous failure to translate preclinical data to clinical practice, and outlines potential paths forward. Post–cardiac arrest brain injury is characterized by 4 distinct but overlapping phases: ischemic depolarization, reperfusion repolarization, dysregulation, and recovery and repair. Previous research has been challenging because of the limitations of laboratory models; heterogeneity in the patient populations enrolled; overoptimistic estimation of treatment effects leading to suboptimal sample sizes; timing and route of intervention delivery; limited or absent evidence that the intervention has engaged the mechanistic target; and heterogeneity in postresuscitation care, prognostication, and withdrawal of life-sustaining treatments. Future trials must tailor their interventions to the subset of patients most likely to benefit and deliver this intervention at the appropriate time, through the appropriate route, and at the appropriate dose. The complexity of post–cardiac arrest brain injury suggests that monotherapies are unlikely to be as successful as multimodal neuroprotective therapies. Biomarkers should be developed to identify patients with the targeted mechanism of injury, to quantify its severity, and to measure the response to therapy. Studies need to be adequately powered to detect effect sizes that are realistic and meaningful to patients, their families, and clinicians. Study designs should be optimized to accelerate the evaluation of the most promising interventions. Multidisciplinary and international collaboration will be essential to realize the goal of developing effective therapies for post–cardiac arrest brain injury.

Branching in poly(amine-co-ester) polyplexes impacts mRNA transfection

Branching is a key structural parameter of polymers, which can have profound impacts on physicochemical properties. It has been demonstrated that branching is a modulating factor for mRNA delivery and transfection using delivery vehicles built from cationic polymers, but the influence of polymer branching on mRNA delivery remains relatively underexplored compared to other polymer features such as monomer composition, hydrophobicity, pKa, or the type of terminal group. In this study, we examined the impact of branching on the physicochemical properties of poly(amine-co-esters) (PACE) and their efficiency in mRNA transfection in vivo and in vitro under various conditions. PACE polymers were synthesized with various degrees of branching ranging from 0 to 0.66, and their transfection efficiency was systemically evaluated. We observed that branching improves the stability of polyplexes but reduces the pH buffering capacity. Therefore, the degree of branching (DB) must be optimized in a delivery route specific manner due to differences in challenges faced by polyplexes in different physiological compartments. Through a systematic analysis of physicochemical properties and mRNA transfection in vivo and in vitro, this study highlights the influence of polymer branching on nucleic acid delivery.

Establishing delivery route-dependent safety and efficacy of living biodrug mesenchymal stem cells in heart failure patients.

Mesenchymal stem cells (MSCs) as living biopharmaceuticals with unique properties, i.e., stemness, viability, phenotypes, paracrine activity, etc., need to be administered such that they reach the target site, maintaining these properties unchanged and are retained at the injury site to participate in the repair process. Route of delivery (RoD) remains one of the critical determinants of safety and efficacy. This study elucidates the safety and effectiveness of different RoDs of MSC treatment in heart failure (HF) based on phase II randomized clinical trials (RCTs). We hypothesize that the RoD modulates the safety and efficacy of MSC-based therapy and determines the outcome of the intervention. To investigate the effect of RoD of MSCs on safety and efficacy in HF patients. RCTs were retrieved from six databases. Safety endpoints included mortality and serious adverse events (SAEs), while efficacy outcomes encompassed changes in left ventricular ejection fraction (LVEF), 6-minute walk distance (6MWD), and pro-B-type natriuretic peptide (pro-BNP). Subgroup analyses on RoD were performed for all study endpoints. Twelve RCTs were included. Overall, MSC therapy demonstrated a significant decrease in mortality [relative risk (RR): 0.55, 95% confidence interval (95%CI): 0.33-0.92, P = 0.02] compared to control, while SAE outcomes showed no significant difference (RR: 0.84, 95%CI: 0.66-1.05, P = 0.11). RoD subgroup analysis revealed a significant difference in SAE among the transendocardial (TESI) injection subgroup (RR = 0.71, 95%CI: 0.54-0.95, P = 0.04). The pooled weighted mean difference (WMD) demonstrated an overall significant improvement of LVEF by 2.44% (WMD: 2.44%, 95%CI: 0.80-4.29, P value ≤ 0.001), with only intracoronary (IC) subgroup showing significant improvement (WMD: 7.26%, 95%CI: 5.61-8.92, P ≤ 0.001). Furthermore, the IC delivery route significantly improved 6MWD by 115 m (WMD = 114.99 m, 95%CI: 91.48-138.50), respectively. In biochemical efficacy outcomes, only the IC subgroup showed a significant reduction in pro-BNP by -860.64 pg/mL (WMD: -860.64 pg/Ml, 95%CI: -944.02 to -777.26, P = 0.001). Our study concluded that all delivery methods of MSC-based therapy are safe. Despite the overall benefits in efficacy, the TESI and IC routes provided better outcomes than other methods. Larger-scale trials are warranted before implementing MSC-based therapy in routine clinical practice.

Time-dependent hydrogen fuel cell vehicle routing problem with drones and variable drone speeds

This paper proposes a novel problem called the time-dependent hydrogen fuel cell vehicle routing problem with drones and variable drone speeds (TDHFCVRP-D-VDS). In this problem, a fleet of hydrogen fuel cell vehicles (HFCVs) are equipped with multiple unmanned aerial vehicles (UAVs) to perform delivery and pickup services within the customers’ time windows. The UAV is capable of performing pickup operations after the delivery service, as long as it does not exceed its energy capacity. The HFCV can launch and retrieve the UAV multiple times as needed throughout the routing process. We establish a mixed integer programming model to simultaneously minimize the total cost and makespan, and verify its accuracy by Gurobi. To tackle larger-scale instances, we propose a non-dominated sorting genetic algorithm III with intelligent selection (NSGA-III-IS). The initial population is generated using four distinct approaches aimed at enhancing both diversity and quality. Considering the customers’ time windows, we factor in the temporal-spatial distances between customers when generating the initial population. Our approach employs a two-phase algorithm for developing initial solutions. In the first phase, the algorithm focuses on generating UAV trips, while in the second phase, it creates joint delivery routes for both the HFCV and the UAV. To enhance the optimization process, we have developed four strategies for optimizing UAV speed. These strategies dynamically adjust the UAV’s speed in response to the customers’ time windows and the HFCVs’ arrival times. Additionally, we have integrated an intelligent selection mechanism to optimize the execution probabilities of both general and problem-specific operators. The experimental results demonstrate the following: (1) The proposed NSGA-III-IS outperforms other variant algorithms and two benchmark algorithms; (2) UAVs significantly benefit from variable flight speeds, resulting in reduced costs and improved efficiency; (3) The HFCV with UAV joint delivery pattern is superior for reducing carbon emissions compared to other joint delivery patterns; (4) Longer customer time windows and optimized UAV speed strategies are effective in reducing the total cost, makespan, and total UAV hover waiting time; (5) Finally, a method that combines multi-attribute decision-making with principal component analysis is utilized to aid decision-makers in selecting satisfactory solutions.

Optimizing delivery routes for sustainable food delivery for multiple food items per order

The diversity of consumer demand for take-out food has led to the characteristic structure of one order with multiple items, where the different food items in a single order are provided by two or more merchants. In the context of multi-item delivery for take-out orders with time windows, this study investigates vehicle routing for order delivery. This research aims to improve the service level of merchants and the efficiency of delivery vehicles. Food vendors receive orders from consumers through online platforms, then package the food items according to the orders. This method is a preliminary exploration of the issue of fulfilment of takeout orders on online platforms, and can provide preliminary theoretical support for decision-making on the delivery process of takeout orders on online platforms. In the context of online catering sales platforms and offline food sales merchants, this paper studies the delivery problem of takeaway orders with a time window and the characteristics of one order and multiple items, and constructs a method that takes the order delivery time requirements into account and minimizes the total order fulfilment cost. Taking into account the time window constraints of both physical restaurants and consumers, genetic algorithms are utilized to solve the order delivery problem. Finally, through case studies and experiments, the effectiveness and feasibility of the mathematical model are validated. Practical recommendations and insights are provided from the perspective of management and route planning.

Gene therapy for CNS disorders: modalities, delivery and translational challenges.

Gene therapy is emerging as a powerful tool to modulate abnormal gene expression, a hallmark of most CNS disorders. The transformative potentials of recently approved gene therapies for the treatment of spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and active cerebral adrenoleukodystrophy are encouraging further development of this approach. However, most attempts to translate gene therapy to the clinic have failed to make it to market. There is an urgent need not only totailor the genes that are targeted to the pathology of interest but to also address delivery challenges and thereby maximize the utility of genetic tools. In this Review, we provide an overview of gene therapy modalities for CNS diseases, emphasizing the interconnectedness of different delivery strategies and routes of administration. Important gaps in understanding that could accelerate the clinical translatability of CNS genetic interventions are addressed, and we present lessons learned from failed clinical trials that may guide the future development of gene therapies for the treatment and management of CNS disorders.

SURG-06. FRAMELESS STEREOTACTIC INTRACRANIAL CATHETER PLACEMENT FOR DELIVERY OF INTRATUMORAL CELLULAR THERAPIES

Abstract BACKGROUND As the leading disease-related cause of death in children, pediatric brain tumors, and in particular diffuse midline glioma, require novel treatment approaches. Cellular-based therapies offer promise, but challenges still exist in defining their optimal delivery route. Emerging data from our group suggest there may be a role for intratumoral injection in treatment algorithms. We here describe a surgical workflow for intratumoral injection of cellular therapies that utilizes existing and widely used neurosurgical technologies that can be incorporated into future clinical trials. METHODS Infusion target and catheter trajectory was planned using standard pre-operative MRI. Components from an FDA-approved frameless stereotactic intracranial biopsy system were chosen such that they would accept and guide an FDA-approved rigid intracranial catheter system intended for MR-guided procedures. Following catheter insertion, an intraoperative CT was used to determine accuracy of catheter placement by merging the image with the pre-operative MRI. RESULTS The proposed system was tested in a simulated fashion using a phantom cranial model registered to an accompanying brain MRI. The stereotactic biopsy mount was affixed to the skull at the planned entry site for a posterior fossa approach to the pons. Catheter insertion depth was determined using the stereotactic system and the catheter was inserted to this depth through the biopsy mount. Intraoperative CT confirmed the catheter tip location which correlated with the planned infusion target with sub-millimetric accuracy. CONCLUSION Our proposed intratumoral delivery method using frameless stereotaxy shows promise for use in future clinical trials that require intratumoral delivery of cellular therapies. Utilizing FDA-approved devices allows for quick integration into protocols and their wide-spread use makes the approach generalizable. This approach also eliminates the need for MR-guided procedures which can increase cost and require significant hospital resources to perform. Future work will be aimed at streamlining the intraoperative workflow.

Design, Synthesis, and Activity Evaluation of Novel Benzazole Bifunctional Antifungal Inhibitors with an LDH Carrier.

Fungal infections maintain a close relation with the body's immune function. In this study, three series of benzazole compounds were designed as dual-target (PD-L1/CYP51) inhibitors using the skeleton splicing approach; their molecular structures were synthesized and evaluated accordingly. Among them, the compounds 9a-2, 12a-2, and 12b-1 exhibited potent antifungal activity and dual-target inhibition ability. Especially, the compound 12a-2 simultaneously exerted excellent bifunctional effects of fungal inhibition and immune activation. Moreover, a layered double hydroxide (LDH) carrier was also successfully constructed based on an infection microenvironment to improve the bioavailability and the targeting of compound 12a-2. This significantly accelerated the recovery process of deep and shallow fungal infections. In conclusion, this study expanded the development horizon of antifungal drugs and provided a novel drug delivery route for treating fungal infections.

Gene therapies for CMT neuropathies: from the bench to the clinic.

Charcot-Marie-Tooth (CMT) neuropathies are rare, genetically heterogeneous and progressive diseases for which there are no approved treatments and their management remains mostly supportive and symptomatic. This review is intended to provide an update on recent developments in gene therapies for different CMT neuropathies. Increasing knowledge of disease pathomechanisms underlying several CMT types has facilitated the development of promising viral and nonviral gene therapy approaches. Some of these therapies are currently approaching the crucial step of moving from the bench to the clinic, having passed the proof-of-concept stage in rodent models and some also in larger animals. However, questions of optimal delivery route and dose, off-target effects, and possible payload toxicity remain to be clarified for several of these approaches. Furthermore, limited resources, the rarity of most CMT subtypes, and issues of safety and regulatory requirements, create the need for consensus guidelines and optimal clinical trial design. Promising gene therapies have been developed for several CMT neuropathies, with proof-of-principle demonstrated in relevant disease models. Advantages and drawbacks of each approach are discussed and remaining challenges are highlighted. Furthermore, we suggest important parameters that should be considered in order to successfully translate them into the clinic.

Embryo transfer impact: a comprehensive national cohort analysis comparing maternal and neonatal outcomes across varied embryo stages in fresh and frozen transfers.

The utilization of frozen embryo transfer not only enhances reproductive outcomes by elevating the likelihood of live birth and clinical pregnancy but also improves safety by mitigating the risks associated with ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. There has been an increasing debate in recent years regarding the advisability of making elective frozen embryo transfer the standard practice. Our study aims to determine the optimal choice between fresh and frozen embryo transfer, as well as whether the transfer should occur at the cleavage or blastocyst stage. In this retrospective cohort study conducted in Taiwan, data from the national assisted reproductive technology (ART) database spanning from January 1st, 2013, to December 31st, 2017, were analyzed. The study included 51,762 eligible female participants who underwent ART and embryo transfer. Pregnancy outcomes, maternal complications, and singleton neonatal outcomes were evaluated using the National Health Insurance Database from January 1st, 2013, to December 31st, 2018. Cases were categorized into groups based on whether they underwent fresh or frozen embryo transfers, with further subdivision into cleavage stage and blastocyst stage transfers. Exposure variables encompassed clinical pregnancy rate, live birth rate, OHSS, pregnancy-induced hypertension, gestational diabetes mellitus (DM), placenta previa, placental abruption, preterm premature rupture of membranes (PPROM), gestational age, newborn body weight, and route of delivery. Frozen blastocyst transfers showed higher rates of clinical pregnancy (CPR) and live births (LBR) compared to fresh blastocyst transfers. Conversely, frozen cleavage stage transfers demonstrated lower rates of clinical pregnancy and live birth compared to fresh cleavage stage transfers. Frozen embryo transfers were associated with reduced risks of OHSS but were linked to a higher risk of pregnancy-induced hypertension compared to fresh embryo transfers. Additionally, frozen embryo transfers were associated with a higher incidence of large for gestational age infants and a lower incidence of small for gestational age infants. The freeze-all strategy may not be suitable for universal application. When embryos can develop to the blastocyst stage, FET is a favorable choice, but embryos can only develop to the cleavage stage, fresh embryo transfer becomes a more reasonable option.

Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo Delivery

AbstractSelf‐assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting‐hydrolysis‐transformation (THT) assembly of glycosylated peptides in living cells holistically resembling viral infection for efficient cargo delivery and combined tumor therapy. We design a glycosylated peptide via incorporating a β‐galactose‐serine residue into bola‐amphiphilic sequences. Co‐assembling of the glycosylated peptide with two counterparts containing irinotecan (IRI) or ligand TSFAEYWNLLSP (PMI) results in formation of the glycosylated co‐assemblies SgVEIP, which target cancer cells via β‐galactose‐galectin‐1 association and undergo galactosidase‐induced morphological transformation. While GSH‐reduction causes release of IRI from the co‐assemblies, the PMI moieties release p53 and facilitate cell death via binding with protein MDM2. Cellular experiments show membrane targeting, endo‐/lysosome‐mediated internalization and in situ formation of nanofibers in cytoplasm by SgVEIP. This cascade THT process enables efficient delivery of IRI and PMI into cancer cells secreting Gal‐1 and overexpressing β‐galactosidase. In vivo studies illustrate enhanced tumor accumulation and retention of the glycosylated co‐assemblies, thereby suppressing tumor growth. Our findings demonstrate an in situ assembly strategy mimicking viral infection, thus providing a new route for drug delivery and cancer therapy in the future.

Assembly of Glycopeptides in Living Cells Resembling Viral Infection for Cargo Delivery.

Self-assembly in living cells represents one versatile strategy for drug delivery; however, it suffers from the limited precision and efficiency. Inspired by viral traits, we here report a cascade targeting-hydrolysis-transformation (THT) assembly of glycosylated peptides in living cells holistically resembling viral infection for efficient cargo delivery and combined tumor therapy. We design a glycosylated peptide via incorporating a β-galactose-serine residue into bola-amphiphilic sequences. Co-assembling of the glycosylated peptide with two counterparts containing irinotecan (IRI) or ligand TSFAEYWNLLSP (PMI) results in formation of the glycosylated co-assemblies SgVEIP, which target cancer cells via β-galactose-galectin-1 association and undergo galactosidase-induced morphological transformation. While GSH-reduction causes release of IRI from the co-assemblies, the PMI moieties release p53 and facilitate cell death via binding with protein MDM2. Cellular experiments show membrane targeting, endo-/lysosome-mediated internalization and in situ formation of nanofibers in cytoplasm by SgVEIP. This cascade THT process enables efficient delivery of IRI and PMI into cancer cells secreting Gal-1 and overexpressing β-galactosidase. In vivo studies illustrate enhanced tumor accumulation and retention of the glycosylated co-assemblies, thereby suppressing tumor growth. Our findings demonstrate an in situ assembly strategy mimicking viral infection, thus providing a new route for drug delivery and cancer therapy in the future.

Analisis Biaya Transportasi dalam Pendistribusian Singkong Menggunakan Metode Northwest Corner dan Least Cost

Transportation plays an important role in supply chain management, where transportation is the process of determining how and when goods should be delivered to consumers. In the transportation method used, it is necessary to consider efficiency and speed in delivering goods. The object of this research is cassava plantations, which are in the Bogor district, especially in the Jonggol, Cariu and Sukamakmur sub-districts. The harvest from this plantation is allocated to 3 factory areas in the Bekasi district. The problem faced is the high transportation costs in allocating the harvest. So, the minimum distribution costs that will be incurred in allocating the harvest to various chip factories are not yet known, and the route and quantity of cassava that will be sent is not yet known. One method of transportation is the Northwest Corner (NWC) and Least Cost Method. The Northwest Corner and Least Cost methods are used in determining goods delivery routes, so that you can calculate the lowest transportation costs from one place to another. Based on the research results, the minimum distribution cost allocated for cassava is IDR 5,410,000.00 with distribution channels namely Cariu to Muktijaya as much as 90 tons, Sukamakmur to Cijengkol as much as 100 tons, Cariu to Ciledug as much as 10 tons, Jonggol to Ciledug as much as 140 tons, and Sukamakmur to Ciledug as much as 20 tons.

Effectiveness of cell therapy of acute radiation syndrome in mice with intravenous and intraperitoneal administration of a cellular product

The therapeutic effect of fibroblast-like cells obtained from the stromal vascular fraction of subcutaneous adipose tissue of mice and cultured for the treatment of bone marrow form of acute radiation syndrome was studied on a mouse experimental model. The cells were identified as multipotent mesenchymal stem (stromal) cells, owing to adhesion to plastic, confluent monolayer formation during cultivation, and the fact that osteogenic differentiation in vitro resulted in osteoblast maturation and calcium deposit formation, which indicated their multipotent nature. Irradiation of laboratory rodents was conducted using theX-ray therapy unit “RUM-17”. Stromal cells were obtained from subcutaneous adipose tissue of a mouse and grown in a culture of 3–4 passages and used as a cell product. Cell transplantation was performed 24 h after uniformX-ray irradiation of mice at a dose of 7.8 Gy. This is the first study to compare the therapeutic efficacy of allogeneic transplantation of multipotent mesenchymal stem cells with the different routes (intravenous and intraperitoneal) of cell suspension administration. A significant increase was found in the survival rate of mice during the 30-day follow-up period after lethal dose irradiation, which depended on the number of injected cells and delivery method of the biomedical cell product. Thus, with intravenous administration of 30 and 60 × 103multipotent mesenchymal stem cells, the 30-day survival rate of mice after irradiation at a dose of 7.8 Gy increased by 54.5% and 40%, respectively, compared with that of untreated animals (p= 0.03). An increase in the number of cells in the cell product to 120 × 103/mouse led to a decrease in therapy effectiveness. In intraperitoneal administration, the protection of animals from death was 57% after transplantation of 30 and 60 × 103cells (p= 0.039) and 50% after application of 120 × 103cells. On day 30 after irradiation, in the introduction of a cellular product in different schemes, 70%–80% of animals showed restoration of the values of the main indicators of the hematopoiesis system to initial levels. Thus, cell therapy using multipotent mesenchymal stem cells isolated from adipose tissue with intravenous and intraperitoneal delivery routes of the cellular product to the irradiated body protects mice from death after exposure toX-ray radiation in lethal doses, decreasing the severity of radiation damage to the hematopoietic system in mice, and provides prospects for further research as an effective and safe treatment for acute radiation sickness.