Delivery Vehicles Research Articles

A bio-ionic liquid based self-healable and adhesive ionic hydrogel for the on-demand transdermal delivery of a chemotherapeutic drug.

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Logistics distribution route optimization of electric vehicles based on distributed intelligent system

Abstract The data management system of health cloud authentication plays an important role in the optimization of logistics vehicle routing. It can not only help logistics vehicles choose the best distribution path, but also save time and cost and improve economic efficiency. At present, logistics has not yet formed a complete service system. High distribution costs and low distribution efficiency limit the development of the entire logistics. The reduction of logistics costs and the improvement of distribution efficiency have become the top priorities of the society. The optimization of the distribution route is the key to cost saving and distribution logistics. It is particularly important to study and optimize the distribution route, because the distribution route affects the logistics transportation efficiency and the loss cost during transportation. Therefore, this paper adjusted the scheduling system of logistics vehicles through a distributed intelligent system, and optimized the path of logistics vehicles according to the improved genetic algorithm, thereby reducing the transportation cost of logistics and improving the efficiency of logistics distribution. This article first explains the definition, classification, and main components of the delivery vehicle routing problem. Then, using cloud authentication path optimization, a distributed intelligent system is constructed. Finally, an improved ant colony algorithm is used to analyze and study the distance constraints of vehicles. By improving the ant colony algorithm, it can be seen that the optimized path pheromone concentration and the optimized sub-function have gradually increased with time. The mean pheromone concentration was 40 %, and the seventh day was 15 % higher than the first. The mean value of the optimized subfunction was 0.34 %, and the seventh day was 20 % higher than the first. The distribution cost and distribution efficiency of the optimized logistics vehicle distribution path were much higher than those of the traditional logistics distribution path. Moreover, the distribution cost of the logistics distribution path was 9 % lower than the traditional one, and the distribution efficiency was 13 % higher. The average smoothness of the optimized logistics path is about 90 %, and the seventh day is 11 % higher than the first day. The average fitness of the optimized logistics path is 88 %, and the seventh day is 14 % higher than the first day. In a word, the data management system can uniformly schedule logistics vehicles and improve the efficiency of distribution.

Conditional Cell Penetration of Masked CPPs by an ADEPT-like Approach.

The intracellular delivery of cargos via cell penetrating peptides (CPPs) holds significant promise as a drug delivery vehicle, but a major issue is their lack of cell type specificity, which can lead to detrimental off-target effects. We use an ADEPT-like concept to introduce conditional and selective activation of cellular uptake by using the lysine-rich, cationic, and amphiphilic L17E peptide as a model CPP. By masking the lysine residues of the L17E peptide with enzyme-cleavable acetyl protecting groups, the delivery of the covalently conjugated fluorophore TAMRA to HeLa cells was diminished. Recovery of cellular uptake could be achieved by deacetylation of the masked acetylated L17E peptide using the NAD-dependent sirtuin 2 (SirT2) deacetylase in vitro. Finally, trastuzumab-SirT2 and anti-B7H3-SirT2 antibody-enzyme conjugates were generated for the conditional and selective delivery of a cryptophycin cytotoxin by the L17E peptide. While the masked peptide still demonstrated some cytotoxicity, selective cell killing mediated by the antibody-enzyme conjugates was observed.

Unveiling the potential of chitosan-coated lipid nanoparticles in drug delivery for management of critical illness: a review.

Chitosan (CT), a natural, cationic, chemically stable molecule, biocompatible, biodegradable, nontoxic, polysaccharide derived from the deacetylation of chitin, has very uniquely surfaced as a material of promise for drug delivery and biomedical applications. For the oral, ocular, cutaneous, pulmonary, and nose-to-brain routes, CT-coated nanoparticles (CTCNPs) have numerous advantages, consisting of improved controlled drug release, physicochemical stability, improved cell and tissue interactions, and increased bioavailability and efficacy of the active ingredient. CTCNPs have a broad range of therapeutic properties including anticancer, antiviral, antifungal, anti-inflammatory, antibacterial properties, treating neurological disorders, and other diseases. This has led to substantial research into the many potential uses of CT as a drug delivery vehicle. CT has also been employed in a wide range of biomedical processes, including bone and cartilage tissue regeneration, ocular tissue regeneration, periodontal tissue regeneration, heart tissue regeneration, and wound healing. Additionally, CT has been used in cosmeceutical, bioimaging, immunization, and gene transfer applications. CT exhibits a number of biological activities, which are the basis for its remarkable potential for use as a drug delivery vehicle, and these activities are covered in detail in this article. The alterations applied to CT to obtain the necessary properties have been described.

Combined helical-blade-strengthened co-flow focusing and high-throughput screening for the synthesis of highly homogeneous nanoliposomes

Nanoliposomes have been widely employed as promising drug delivery vehicles for the treatment of various diseases. However, the large-scale synthesis of drug-loaded nanoliposomes manifesting a highly uniform particle size is impeded by several unmet challenges. Herein a novel helical-blade-strengthened co-flow focusing (HBSCF) device was developed by installing multiple parallel helical blades in a commonly used co-flow focusing microfluidic device. This transformation in the microchannel structure may accelerate the mixing of aqueous and lipid streams in a radial direction, thereby affording the production of nanoliposomes with a significantly lower polydispersity index (PDI) value in terms of particle size. Moreover, a high-throughput experimental platform was developed by employing HBSCF device alongside its integration with various automation modules, which afforded 672 distinct experimental schemes for the synthesis and size characterization of drug-loaded nanoliposomes within 40 h. Afterwards, based on the above obtained large data set of nanoliposomes, a typical machine learning (ML) model pertaining to particle size was established to predict candidate synthesis schemes for the desired average particle size. Therefore, by narrowing the screening ranges through ML, the final synthesis scheme capable of producing liposomes with the desired particle size along with minimum PDI value can be precisely and rapidly obtained using automated experiments based on the same platform. Taken together, an effective integration of the HBSCF synthesis along with an automated high-throughput experimental platform may have broad implications for the industrialization and clinical application of nanomedicine.

Exploring the Localization of Siderophore-Mediated Cargo Delivery in Gram-Negative Bacteria Using 3-Hydroxypyridin-4(1H)-one-Fluorescein Probes.

The design of siderophore-antibiotic conjugates is a promising strategy to overcome drug resistance in negative bacteria. However, accumulating studies have shown that only those antibiotics acting on the cell wall or cell membrane multiply their antibacterial effects when coupled with siderophores, while antibiotics acting on targets in the cytoplasm of bacteria do not show an obvious enhancement of their antibacterial effects when coupled with siderophores. To explore the causes of this phenomenon, we synthesized several conjugate probes using 3-hydroxypyridin-4(1H)-ones as siderophores and replacing the antibiotic cargo with 5-carboxyfluorescein (5-FAM) or malachite green (MG) cargo. By monitoring changes in the fluorescence intensity of FAM conjugate 20 in bacteria, the translocation of the conjugate across the outer membranes of Gram-negative pathogens was confirmed. Further, the use of the fluorogen activating protein(FAP)/MG system revealed that 3-hydroxypyridin-4(1H)-one-MG conjugate 26 was ultimately distributed mainly in the periplasm rather than being translocated into the cytosol of Escherichia coli and Pseudomonas aeruginosa PAO1. Additional mechanistic studies suggested that the uptake of the conjugate involved the siderophore-dependent iron transport pathway and the 3-hydroxypyridin-4(1H)-ones siderophore receptor-dependent mechanism. Meanwhile, we demonstrated that the conjugation of 3-hydroxypyridin-4(1H)-ones to the fluorescein 5-FAM can reduce the possibility of the conjugates crossing the membrane layers of mammalian Vero cells by passive diffusion, and the advantages of the mono-3-hydroxypyridin-4(1H)-ones as a delivery vehicle in the design of conjugates compared to the tri-3-hydroxypyridin-4(1H)-ones. Overall, this work reveals the localization rules of 3-hydroxypyridin-4(1H)-ones as siderophores to deliver the cargo into Gram-negative bacteria. It provides a theoretical basis for the subsequent design of siderophore-antibiotic conjugates, especially based on 3-hydroxypyridin-4(1H)-ones as siderophores.

Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation

AbstractLong‐lasting vaginal dosage forms could improve the therapeutic efficacy of vaginal microbicides, but achieving long‐term delivery to the vaginal canal has been a significant challenge. To advance understanding of vaginal dosage retention and biodistribution, we describe a method of noninvasive imaging with 89Zr‐labeled bioadhesive nanoparticles (BNPs) in non‐human primates. We additionally examined the safety of repeated BNP application. BNPs administered vaginally to cynomolgus monkeys were still detected after 24 h (1.7% retention) and 120 h (0.1% retention). BNPs did not translocate to the uterus or into systemic circulation. Analysis of inflammatory biomarkers in the vaginal fluid and plasma suggest that BNPs are safe and biocompatible, even after multiple doses. BNPs are a promising delivery vehicle for vaginally administered therapeutics. Further studies using the non‐human primate imaging materials and methods developed here could help advance clinical translation of BNPs and other long‐lasting vaginal dosage forms.

Ultra-fast in vivo directional dark-field x-ray imaging for visualising magnetic control of particles for airway gene delivery

Objective. Magnetic nanoparticles can be used as a targeted delivery vehicle for genetic therapies. Understanding how they can be manipulated within the complex environment of live airways is key to their application to cystic fibrosis and other respiratory diseases. Approach. Dark-field x-ray imaging provides sensitivity to scattering information, and allows the presence of structures smaller than the detector pixel size to be detected. In this study, ultra-fast directional dark-field synchrotron x-ray imaging was utlilised to understand how magnetic nanoparticles move within a live, anaesthetised, rat airway under the influence of static and moving magnetic fields. Main results. Magnetic nanoparticles emerging from an indwelling tracheal cannula were detectable during delivery, with dark-field imaging increasing the signal-to-noise ratio of this event by 3.5 times compared to the x-ray transmission signal. Particle movement as well as particle retention was evident. Dynamic magnetic fields could manipulate the magnetic particles in situ. Significance. This is the first evidence of the effectiveness of in vivo dark-field imaging operating at these spatial and temporal resolutions, used to detect magnetic nanoparticles. These findings provide the basis for further development toward the effective use of magnetic nanoparticles, and advance their potential as an effective delivery vehicle for genetic agents in the airways of live organisms.

Characterizing Glycosylation of Adeno-Associated Virus Serotype 9 Capsid Proteins Generated from HEK293 Cells through Glycopeptide Mapping and Released Glycan Analysis

Recombinant adeno-associated viral (AAV) vectors have emerged as prominent gene delivery vehicles for gene therapy. AAV capsid proteins determine tissue specificity and immunogenicity and play important roles in receptor binding, the escape of the virus from the endosome, and the transport of the viral DNA to the nuclei of target cells. Therefore, the comprehensive characterization of AAV capsid proteins is necessary for a better understanding of the vector assembly, stability, and transduction efficiency of AAV gene therapies. Glycosylation is one of the most common post-translational modifications (PTMs) and may affect the tissue tropism of AAV gene therapy. However, there are few studies on the characterization of the N- and O-glycosylation of AAV capsid proteins. In this study, we identified the N- and O-glycosylation sites and forms of AAV9 capsid proteins generated from HEK293 cells using liquid chromatography–tandem mass spectrometry (LC-MS)-based glycopeptide mapping and identified free N-glycans released from AAV9 capsid proteins by PNGase F using hydrophilic interaction (HILIC) LC-MS and HILIC LC-fluorescence detection (FLD) methods. This study demonstrates that AAV9 capsids are sprinkled with sugars, including N- and O-glycans, albeit at low levels. It may provide valuable information for a better understanding of AAV capsids in supporting AAV-based gene therapy development.

Computational fluid dynamics based digital twins of fixed bed bioreactors validate scaling principles for recombinant adeno-associated virus gene therapy manufacturing.

Gene therapy using recombinant adeno-associated virus (rAAV) as delivery vehicles has garnered much interest in recent years. There are still significant gaps in our fundamental understanding of the manufacturing processes to deliver sufficient products. Manufacturing efforts of rAAV using HEK293 cells have commonly relied on fixed bed falling film bioreactors like the iCELLis®. We used computational fluid dynamics (CFD) to validate the operating conditions required for a predictive iCELLis® 500 scale-down model. The small-scale and at-scale systems have different flow paths causing validation of the corresponding agitation rates required to achieve the same linear flow through the fixed bed across scales to be non-trivial. Therefore, we used CFD to predict the theoretical scaling relationship. In addition, CFD could predict kLa differences between the two systems and the operating conditions required to match kLa between scales. We also confirmed that the location of DO control must be the same in both systems to achieve proper scaling. Experimental runs confirming the validity of the novel scale-down model showed that based on the modifications to the iCELLis® Nano system, we achieved similar DO, key metabolite, pH, and GC titer trends in both systems.

Receptor Targeting Using Copolymer-Modified Gold Nanoparticles for pCMV-Luc Gene Delivery to Liver Cancer Cells In Vitro.

The formulation of novel delivery protocols for the targeted delivery of genes into hepatocytes by receptor mediation is important for the treatment of liver-specific disorders, including cancer. Non-viral delivery methods have been extensively studied for gene therapy. Gold nanoparticles (AuNPs) have gained attention in nanomedicine due to their biocompatibility. In this study, AuNPs were synthesized and coated with polymers: chitosan (CS), and polyethylene glycol (PEG). The targeting moiety, lactobionic acid (LA), was added for hepatocyte-specific delivery. Physicochemical characterization revealed that all nano-formulations were spherical and monodispersed, with hydrodynamic sizes between 70 and 250 nm. Nanocomplexes with pCMV-Luc DNA (pDNA) confirmed that the NPs could bind, compact, and protect the pDNA from nuclease degradation. Cytotoxicity studies revealed that the AuNPs were well tolerated (cell viabilities > 70%) in human hepatocellular carcinoma (HepG2), embryonic kidney (HEK293), and colorectal adenocarcinoma (Caco-2) cells, with enhanced transgene activity in all cells. The inclusion of LA in the NP formulation was notable in the HepG2 cells, which overexpress the asialoglycoprotein receptor on their cell surface. A five-fold increase in luciferase gene expression was evident for the LA-targeted AuNPs compared to the non-targeted AuNPs. These AuNPs have shown potential as safe and suitable targeted delivery vehicles for liver-directed gene therapy.

Mesoporous Silica Nanoparticles as an Ideal Platform for Cancer Immunotherapy: Recent Advances and Future Directions.

Cancer immunotherapy recently transforms the traditional approaches against various cancer malignancies. Immunotherapy includes systemic and local treatments to enhance immune responses against cancer and involves strategies such as immune checkpoints, cancer vaccines, immune modulatory agents, mimetic antigen-presenting cells, and adoptive cell therapy. Despite promising results, these approaches still suffer from several limitations including lack of precise delivery of immune-modulatory agents to the target cells and off-target toxicity, among others, that can be overcome using nanotechnology. Mesoporous silica nanoparticles (MSNs) are investigated to improve various aspects of cancer immunotherapy attributed to the advantageous structural features of this nanomaterial. MSNs can be engineered to alter their properties such as size, shape, porosity, surface functionality, and adjuvanticity. This review explores the immunological properties of MSNs and the use of MSNs as delivery vehicles for immune-adjuvants, vaccines, and mimetic antigen-presenting cells (APCs). The review also details the current strategies to remodel the tumor microenvironment to positively reciprocate toward the anti-tumor immune cells and the use of MSNs for immunotherapy in combination with other anti-tumor therapies including photodynamic/thermal therapies to enhance the therapeutic effect against cancer. Last, the present demands and future scenarios for the use of MSNs for cancer immunotherapy are discussed.

Human-Derived collagen hydrogel as an antibiotic vehicle for topical treatment of bacterial biofilms.

The complexity of chronic wounds creates difficulty in effective treatments, leading to prolonged care and significant morbidity. Additionally, these wounds are incredibly prone to bacterial biofilm development, further complicating treatment. The current standard treatment of colonized superficial wounds, debridement with intermittent systemic antibiotics, can lead to systemic side-effects and often fails to directly target the bacterial biofilm. Furthermore, standard of care dressings do not directly provide adequate antimicrobial properties. This study aims to assess the capacity of human-derived collagen hydrogel to provide sustained antibiotic release to disrupt bacterial biofilms and decrease bacterial load while maintaining host cell viability and scaffold integrity. Human collagen harvested from flexor tendons underwent processing to yield a gellable liquid, and subsequently was combined with varying concentrations of gentamicin (50-500 mg/L) or clindamycin (10-100 mg/L). The elution kinetics of antibiotics from the hydrogel were analyzed using liquid chromatography-mass spectrometry. The gel was used to topically treat Methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium perfringens in established Kirby-Bauer and Crystal Violet models to assess the efficacy of bacterial inhibition. 2D mammalian cell monolayers were topically treated, and cell death was quantified to assess cytotoxicity. Bacteria-enhanced in vitro scratch assays were treated with antibiotic-embedded hydrogel and imaged over time to assess cell death and mobility. Collagen hydrogel embedded with antibiotics (cHG+abx) demonstrated sustained antibiotic release for up to 48 hours with successful inhibition of both MRSA and C. perfringens biofilms, while remaining bioactive up to 72 hours. Administration of cHG+abx with antibiotic concentrations up to 100X minimum inhibitory concentration was found to be non-toxic and facilitated mammalian cell migration in an in vitro scratch model. Collagen hydrogel is a promising pharmaceutical delivery vehicle that allows for safe, precise bacterial targeting for effective bacterial inhibition in a pro-regenerative scaffold.

A versatile delivery vehicle for cellular oxygen and fuels, or metabolic sensor? - A review and perspective on the functions of myoglobin.

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O2) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O2 partial pressure (pO2) drops and Mb offloads O2. Besides O2 storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR) , and "ectopic" expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb-/-) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes. From these and other findings in the literature over many decades, Mb's function is not confined to delivering O2 in support of oxidative phosphorylation, but also to serve as an O2-sensor that modulates intracellular pO2- and NO-responsive molecular signaling pathways. This paradigm reflects a fundamental change in how oxidative metabolism and cell regulation are viewed in Mb-expressing cells such as skeletal muscle, heart, brown adipocytes, and select cancer cells. Herein, we review historic and emerging views related to the physiological roles for Mb, and present working models illustrating the possible importance of interactions between Mb, gases, and small molecule metabolites in regulation of cell signaling and bioenergetics.

Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress

Sigma-2-ligands (S2L) are characterized by high binding affinities to their cognate sigma-2 receptor, overexpressed in rapidly proliferating tumor cells. As such, S2L were developed as imaging probes (ISO1) or as cancer therapeutics, alone (SV119 [C6], SW43 [C10]) and as delivery vehicles for cytotoxic drug cargoes (C6-Erastin, C10-SMAC). However, the exact mechanism of S2L-induced cytotoxicity remains to be fully elucidated. A series of high-affinity S2L were evaluated regarding their cytotoxicity profiles across cancer cell lines. While C6 and C10 displayed distinct cytotoxicities, C0 and ISO1 were essentially non-toxic. Confocal microscopy and lipidomics analysis in cellular and mouse models revealed that C10 induced increases in intralysosomal free cholesterol and in cholesterol esters, suggestive of unaltered intracellular cholesterol trafficking. Cytotoxicity was caused by cholesterol excess, a phenomenon that contrasts the effects of NPC1 inhibition. RNA-sequencing revealed gene clusters involved in cholesterol homeostasis and ER stress response exclusively by cytotoxic S2L. ER stress markers were confirmed by qPCR and their targeted modulation inhibited or enhanced cytotoxicity of C10 in a predicted manner. Moreover, C10 increased sterol regulatory element-binding protein 2 (SREBP2) and low-density lipoprotein receptor (LDLR), both found to be pro-survival factors activated by ER stress. Furthermore, inhibition of downstream processes of the adaptive response to S2L with simvastatin resulted in synergistic treatment outcomes in combination with C10. Of note, the S2L conjugates retained the ER stress response of the parental ligands, indicative of cholesterol homeostasis being involved in the overall cytotoxicity of the drug conjugates. Based on these findings, we conclude that S2L-mediated cell death is due to free cholesterol accumulation that leads to ER stress. Consequently, the cytotoxic profiles of S2L drug conjugates are proposed to be enhanced via concurrent ER stress inducers or simvastatin, strategies that could be instrumental on the path toward tumor eradication.

Subconjunctival injection of rapamycin-loaded polymeric microparticles for effective suppression of noninfectious uveitis in rats

Noninfective uveitis is a major cause of vision impairment, and corticosteroid medication is a mainstay clinical strategy that causes severe side effects. Rapamycin (RAPA), a potent immunomodulator, is a promising treatment for noninfective uveitis. However, because high and frequent dosages are required, it is a great challenge to implement its clinical translation for noninfective uveitis therapy owing to its serious toxicity. In the present study, we engineered an injectable microparticulate drug delivery system based on biodegradable block polymers (i.e., polycaprolactone-poly (ethylene glycol)-polycaprolactone, PCEC) for efficient ocular delivery of RAPA via a subconjunctival injection route and investigated its therapeutic efficacy in an experimental autoimmune uveitis (EAU) rat model. RAPA-PCEC microparticles were fabricated using the emulsion-evaporation method and thoroughly characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The formed microparticles exhibited slow in vitro degradation over 28 days, and provided both in vitro and in vivo sustained release of RAPA over 4 weeks. Additionally, a single subconjunctival injection of PCEC microparticles resulted in high ocular tolerance. More importantly, subconjunctival injection of RAPA-PCEC microparticles significantly attenuated the clinical signs of EAU in a dose-dependent manner by reducing inflammatory cell infiltration (i.e., CD45+ cells and Th17 cells) and inhibiting microglial activation. Overall, these injectable microparticulate systems may be promising vehicles for intraocular delivery of RAPA for the treatment of noninfective uveitis.

Recent advances on two-dimensional material-based nanosystems for gene delivery

Gene therapy has been extensively investigated and widely used in biomedical fields, such as cancer treatment. However, the most important issues for gene therapy are stability, targeting effect, transfection efficacy, and safety of gene formulation after administration, which seriously limit the further application of gene therapy in clinic. Therefore, gene delivery could be a promising strategy for overcoming these challenges. Two-dimensional (2D) materials are rising nanomaterials with excellent physical and chemical properties, including large specific surface area, easy modification, high conversion efficiency of light, and good biocompatibility, which have achieved promising applications as vehicles for gene delivery in the disease treatment. In this review, we first summarized the research progress of 2D material-based nanosystems for gene delivery to improve the therapeutic efficacy. We discussed that 2D material-based gene delivery nanosystems showed high therapeutic efficacy for many diseases treatment, especially cancer. Furthermore, we also proposed that surface modification of 2D materials might be a promising strategy to prepare multi-functional gene carriers for combination therapy with enhanced treatment efficacy. Finally, the future research progress, challenges, and prospects of 2D material-based nanosystems for gene therapy were discussed and concluded. Conclusively, we believe that 2D material-based nanosystems with good biocompatibility and high transfection efficiency would be potentially used in clinical settings to improve the therapeutic efficacy of gene therapy.

Biosynthesis and Characterization of Curcumin Loaded CdO-SiO2@Chitosan Nanocomposite: Multifunctional Agent for Enhanced Drug Delivery Vehicles for Cancer Therapy

Biosynthesis and Characterization of Curcumin Loaded CdO-SiO2@Chitosan Nanocomposite: Multifunctional Agent for Enhanced Drug Delivery Vehicles for Cancer Therapy

Metal organic framework-based polymeric hydrogel: A promising drug delivery vehicle for the treatment of breast cancer

The constraints associated with current cancer therapies have inspired scientists to develop advanced, precise, and safe drug delivery methods. These delivery systems boost treatment effectiveness, minimize harm to healthy cells, and combat cancer recurrence. To design advanced drug delivery vehicle with these character, in the present manuscript, we have designed a self-healing and injectable hybrid hydrogel through synergistically interacting metal organic framework, CuBTC with the poly(vinyl alcohol) (PVA). This hybrid hydrogel acts as a localized drug delivery system and was used to encapsulate and release the anticancer drug 5-Fluorouracil selectively at the targeted site in response to the physiological pH. The hydrogel was formed through transforming the gaussian coil like matrix of PVA-CuBTC into a three-dimensional network of hydrogel upon the addition of crosslinker; borax. The biocompatible character of the hydrogel was confirmed through cell viability test. The biocompatible hybrid hydrogel then was used to encapsulate and studied for the pH responsive release behavior of the anti-cancer drug, 5-FU. The in vitro cytotoxicity of the drug-loaded hydrogel was evaluated against MCF-7 and HeLa cells. The study confirms that the hybrid hydrogel is effective for targeted and sustained release of anticancer drugs at cancer sites.

Manajemen Risiko Rantai Pasok Produk Halal Pada Komoditas Daging Ayam

This study aims to analyze the supply chain management of halal products in the Yogyakarta Chicken Processing Region. The type of research used is a combination model/concurrent embedded design research. The method of House of Risk as the integration of Failure Models and Effect Analysis (FMEA) method was used in this research. The results of the research showed that the percentage of risk agents was used as the main factors including the risk agent A26, (Narrow Production Space) with a percentage of 12%, A27 with a percentage of 12% (Over Stock Capacity), A20 (negligence of the officer infollowing the SOP), A31 (Product damaged in shipping), A32 (Bad delivery vehicle), A34 (Company compensation to consumers for not meeting the consumer demand). Based on the results of calculations in the House of Risk model phase 2, the ranking of preventive actions that must be carried out first includes (PA 4) conducting training for workers, (PA 3) adding refrigeration machines, (PA 1) expanding production, (PA6) leasing transportation equipment, (PA2) managing production capacity, (PA7) having a clear agreement regarding the sale and purchase agreement.