Delivery System Research Articles

Unleashing the power of chlorogenic acid: exploring its potential in nutrition delivery and the food industry.

In the contemporary era, heightened emphasis on health and safety has emerged as a paramount concern among individuals with food. The concepts of "natural" and "green" have progressively asserted dominance in the food consumption market. Consequently, through continuous exploration and development, an escalating array of natural bioactive ingredients is finding application in both nutrition delivery and the broader food industry. Chlorogenic acid (CGA), a polyphenolic compound widely distributed in various plants in nature, has garnered significant attention. Abundant research underscores CGA's robust biological activity, showcasing notable preventive and therapeutic efficacy across diverse diseases. This article commences with a comprehensive overview, summarizing the dietary sources and primary biological activities of CGA. These encompass antioxidant, anti-inflammatory, antibacterial, anti-cancer, and neuroprotective activities. Next, a comprehensive overview of the current research on nutrient delivery systems incorporating CGA is provided. This exploration encompasses nanoparticle, liposome, hydrogel, and emulsion delivery systems. Additionally, the article explores the latest applications of CGA in the food industry. Serving as a cutting-edge theoretical foundation, this paper contributes to the design and development of CGA in the realms of nutrition delivery and the food industry. Finally, the article presents informed speculations and considerations for the future development of CGA.

Synthesis of novel coumarin-triazole hybrids and first evaluation of the 4-phenyl substituted hybrid loaded PLGA nanoparticles delivery system to the anticancer activity.

Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound21which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 ± 2.96 nm, -16.90 ± 0.85 mV zeta potential, and 4.12 ± 0.90% drug loading capacity. The obtained21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV-vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. Thein vitrorelease of21from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively.21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than21. The IC50 values were determined as IC50(21-loaded PLGA nanoparticles): 0.42 ± 0.01 mg ml-1and IC50(free21molecule): 5.74 ± 3.82 mg ml-1against MCF-7 cells, and as IC50(21-loaded PLGA nanoparticles): 0.77 ± 0.12 mg ml-1and IC50(free21molecule): 1.32 ± 0.31 mg ml-1against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

Modern trends in the formulation of microparticles for lung delivery using porogens: methods, principles and examples.

Inhalation drug administration is increasingly used for local pharmacotherapy of lung disorders and as an alternative route for systemic drug delivery. Modern inhalation powder systems aim to target drug deposition in the required site of action. Large porous particles (LPP), characterized by an aerodynamic diameter over 5 μm, density below 0.4 g/cm3, and the ability to avoid protective lung mechanisms, come to the forefront of the research. They are mostly prepared by spray techniques such as spray drying or lyophilization using pore-forming substances (porogens). These substances could be gaseous, solid, or liquid, and their selection depends on their polarity, solubility, and mutual compatibility with the carrier material and the drug. According to the pores-forming mechanism, porogens can be divided into groups, such as osmogens, extractable porogens, and porogens developing gases during decomposition. This review characterizes modern trends in the formulation of solid microparticles for lung delivery; describes the mechanisms of action of the most often used porogens, discusses their applicability in various formulation methods, emphasizes spray techniques; and documents discussed topics by examples from experimental studies.

Ti3C2 (MXene), an advanced carrier system: role in photothermal, photoacoustic, enhanced drugs delivery and biological activity in cancer therapy.

In the realm of healthcare and the advancing field of medical sciences, the development of efficient drug delivery systems become an immense promise to cure several diseases. Despite considerable advancements in drug delivery systems, numerous challenges persist, necessitating further enhancements to optimize patient outcomes. Smart nano-carriers, for instance, 2D sheets nano-carriers are the recently emerging nanosheets that may garner attention for targeted delivery of bioactive compounds, drugs, and genes to kill cancer cells. Within these advancements, Ti3C2TX-MXene, characterized as a two-dimensional transition metal carbide, has surfaced as a prominent intelligent nanocarrier within nanomedicine. Its noteworthy characteristics facilitated it as an ideal nanocarrier for cancer therapy. In recent advancements in drug delivery research, Ti3C2TX-MXene 2D nanocarriers have been designed to release drugs in response to specific stimuli, guided by distinct physicochemical parameters. This review emphasized the multifaceted role of Ti3C2TX-MXene as a potential carrier for delivering poorly hydrophilic drugs to cancer cells, facilitated by various polymer coatings. Furthermore, beyond drug delivery, this smart nanocarrier demonstrates utility in photoacoustic imaging and photothermal therapy, further highlighting its significant role in cellular mechanisms.

Beyond nanoparticle-based oral drug delivery: transporter-mediated absorption and disease targeting.

Various strategies at the microscale/nanoscale have been developed to improve oral absorption of therapeutics. Among them, gastrointestinal (GI)-transporter/receptor-mediated nanosized drug delivery systems (NDDSs) have drawn attention due to their many benefits, such as improved water solubility, improved chemical/physical stability, improved oral absorption, and improved targetability of their payloads. Their therapeutic potential in disease animal models (e.g., solid tumors, virus-infected lungs, metastasis, diabetes, and so on) has been investigated, and could be expanded to disease targeting after systemic/lymphatic circulation, although the detailed paths and mechanisms of endocytosis, endosomal escape, intracellular trafficking, and exocytosis through the epithelial cell lining in the GI tract are still unclear. Thus, this review summarizes and discusses potential GI transporters/receptors, their absorption and distribution, in vivo studies, and potential sequential targeting (e.g., oral absorption and disease targeting in organs/tissues).

Biomaterials-based Technologies in Skeletal Muscle Tissue Engineering.

For many clinically prevalent severe injuries, the inherent regenerative capacity of skeletal muscle remains inadequate. Skeletal muscle tissue engineering (SMTE) seeks to meet this clinical demand. With continuous progress in biomedicine and related technologies including micro/nanotechnology and 3D printing, numerous studies have uncovered various intrinsic mechanisms regulating skeletal muscle regeneration and developed tailored biomaterial systems based on these understandings. Here, we discussed the skeletal muscle structure and regeneration process and explored in detail the diverse biomaterial systems derived from various technologies. Biomaterials serve not merely as local niches for cell growth, but also as scaffolds endowed with structural or physicochemical properties that provide tissue regenerative cues such as topographical, electrical, and mechanical signals. They can also act as delivery systems for stem cells and bioactive molecules that have been shown as key participants in endogenous repair cascades. To achieve bench-to-bedside translation, we have also summarized the typical effect enabled by biomaterial systems and the potential underlying molecular mechanisms. We hope to provide insights into the roles of biomaterials in SMTE from cellular and molecular perspectives. Finally, we provided perspectives on the advancement of SMTE, for which gene therapy, exosomes, and hybrid biomaterials may hold promise to make important contributions. This article is protected by copyright. All rights reserved.

In Vivo Delivery of Spherical and Cylindrical In Vitro Reconstituted Virus-like Particles Containing the Same Self-Amplifying mRNA.

The dramatic effectiveness of recent mRNA (mRNA)-based COVID vaccines delivered in lipid nanoparticles has highlighted the promise of mRNA therapeutics in general. In this report, we extend our earlier work on self-amplifying mRNAs delivered in spherical in vitro reconstituted virus-like particles (VLPs), and on drug delivery using cylindrical virus particles. In particular, we carry out separate in vitro assemblies of a self-amplifying mRNA gene in two different virus-like particles: one spherical, formed with the capsid protein of cowpea chlorotic mottle virus (CCMV), and the other cylindrical, formed from the capsid protein of tobacco mosaic virus (TMV). The mRNA gene is rendered self-amplifying by genetically fusing it to the RNA-dependent RNA polymerase (RdRp) of Nodamura virus, and the relative efficacies of cell uptake and downstream protein expression resulting from their CCMV- and TMV-packaged forms are compared directly. This comparison is carried out by their transfections into cells in culture: expressions of two self-amplifying genes, enhanced yellow fluorescent protein (EYFP) and Renilla luciferase (Luc), packaged alternately in CCMV and TMV VLPs, are quantified by fluorescence and chemiluminescence levels, respectively, and relative numbers of the delivered mRNAs are measured by quantitative real-time PCR. The cellular uptake of both forms of these VLPs is further confirmed by confocal microscopy of transfected cells. Finally, VLP-mediated delivery of the self-amplifying-mRNA in mice following footpad injection is shown by in vivo fluorescence imaging to result in robust expression of EYFP in the draining lymph nodes, suggesting the potential of these plant virus-like particles as a promising mRNA gene and vaccine delivery modality. These results establish that both CCMV and TMV VLPs can deliver their in vitro packaged mRNA genes to immune cells and that their self-amplifying forms significantly enhance in situ expression. Choice of one VLP (CCMV or TMV) over the other will depend on which geometry of nucleocapsid is self-assembled more efficiently for a given length and sequence of RNA, and suggests that these plant VLP gene delivery systems will prove useful in a wide variety of medical applications, both preventive and therapeutic.

Trackable Liposomes for In Vivo Delivery Tracing toward Personalized Medicine Care under NIR Light on Skin Tumor.

We report an near-infrared (NIR)-trackable and therapeutic liposome with skin tumor specificity. Liposomes with a hydrodynamic diameter of ∼20 nm are tracked under the vein visualization imaging system in the presence of loaded paclitaxel and NIR-active agents. The ability to track liposome nanocarriers is recorded on the tissue-mimicking phantom model and in vivo mouse veins after intravenous administration. The trackable liposome delivery provides in vitro and in vivo photothermal heat (∼40 °C) for NIR-light-triggered area-specific chemotherapeutic release. This approach can be linked with a real-time vein-imaging system to track and apply area-specific local heat, which hitchhikes liposomes from the vein and finally releases them at the tumor site. We conducted studies on mice skin tumors that indicated the disappearance of tumors visibly and histologically (H&E stains). The ability of nanocarriers to monitor after administration is crucial for improving the effectiveness and specificity of cancer therapy, which could be achieved in the trackable delivery system.

Designing of a new transdermal antibiotic delivery polymeric membrane modified by functionalized SBA-15 mesoporous filler

A new drug delivery system using an asymmetric polyethersulfone (PES) membrane modified by SBA-15 and glutamine-modified SBA-15 (SBA-Q) was prepared in this study by the aim of azithromycin delivery enhancement in both in vitro and ex vivo experiments. The research focused on optimizing membrane performance by adjusting critical parameters including drug concentration, membrane thickness, modifier percentage, polymer percentage, and pore maker percentage. To characterize the fabricated membranes, various techniques were employed, including scanning electron microscopy, water contact angle, and tensile strength assessments. Following optimization, membrane composition of 17% PES, 2% polyvinylpyrrolidone, 1% SBA-15, and 0.5% SBA-Q emerged as the most effective. The optimized membranes demonstrated a substantial increase in drug release (906 mg/L) compared to the unmodified membrane (440 mg/L). The unique membrane structure, with a dense top layer facilitating sustained drug release and a porous sub-layer acting as a drug reservoir, contributed to this improvement. Biocompatibility assessments, antibacterial activity analysis, blood compatibility tests, and post-diffusion tissue integrity evaluations confirmed the promising biocompatibility of the optimized membranes. Moreover, long-term performance evaluations involving ten repeated usages underscored the reusability of the optimized membrane, highlighting its potential for sustained and reliable drug delivery applications.

Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150nm, a negative zeta potential of -35mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Stimuli-Responsive Dendrimers as Nanoscale Vectors in Drug and Gene Delivery Systems: A Review Study

Stimuli-Responsive Dendrimers as Nanoscale Vectors in Drug and Gene Delivery Systems: A Review Study

Advancing Novel Strategies against Post-surgical Tendon Adhesion Bands, Exploring New Frontiers.

Current interest in adhesion formation stems from its global impact on the function and quality of life, spanning a spectrum of subtle impairments to significant disabilities, based on the affected area and the extent of adhesion. Yet therapeutic agents are restricted to prophylactic anti-inflammatories, revision surgeries, and biological and physical techniques, none of which grant a decent outcome. Recent advancements in tissue- engineered biomaterials, drug delivery systems, and fabricating technologies such as nanoparticles, hydrogels, and weaving or braiding demonstrate potential for improved outcomes. However, none of the mentioned methods have reliable outcomes, thus this study aims to elucidate the mechanisms involved in the pathophysiology of tendon adhesion and post-surgical adhesion band formation (PSAB), with a closer look at inflammatory pathways stimulating the process. This article consolidates information on diverse therapeutic and prophylactic methods and cutting-edge technologies, aiming to provide a comprehensive update on this topic, and providing researchers an avenue for new and innovative ideas for further investigations.

Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.

Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.

Novel in silico nano-drug design and delivery systems employing the density functional theory: a review

Novel in silico nano-drug design and delivery systems employing the density functional theory: a review

Preparation and characterization of nanoparticles loaded with dimethyl fumarate for the treatment of multiple sclerosis

When nanotechnology is used in medicine, it makes it easier to find and treat a wide range of diseases. One of the oral options for treating multiple sclerosis (MS) is dimethyl fumarate (DMF). DMF has been shown to be effective in lowering inflammatory diseases; nevertheless, it is characterized by several undesirable side effects that reduce pa¬tient compliance and add financial obstacles. The aim of this study was to use platelet membranes and platelet na¬noparticles to generate a drug delivery system that works like a cell, so as to treat MS. During the experiments, there is a chance that the DMF solution might harden at room temperature. Therefore, in order to produce solid lipid nano¬particles (SLNs), DMF was combined with biocompatible lipids. The creation of SLNs involved the use of hot emulsion and ultrasonication. These DMF-SLNs were characterized by means of scanning electron microscopy, and Fourier-transform infrared spectroscopy. The herein demonstrated enhanced qualities of the devised SLNs suggest that the formulation may be a potential, longer-acting formulation for the improved management of MS. SLNs could change the way many illnesses are treated in a big way, if they are used for the delivery of medicines.

Inorganic polymers as drug carriers: opportunities and challenges

Innovative methods and significant developments in designing new synthetic inorganic materials have been used to overcome limitations of current drug delivery systems. Inorganic polymers are widely used in the field of biomedicine, imaging, tissue engineering and drug delivery because of their bioactivity, biocompatibility, and stability. A few of the more well-known wholly inorganic polymers are portland cement, silicon dioxide, polyanionic glasses (including titania- and aluminosilicate glasses), poly(sulphur nitride), polycrystalline diamond, graphite, poly(sulphur nitride), and alumi¬num-silicate materials. Inorganic polymers, especially those possessing significant porosity, are good potential candi¬dates for the delivery of several drugs (anticancer, antibiotics, and anti-inflammatories), providing advantages such as encapsulation, controlled delivery, and improved targeting of drugs. Choosing a suitable drug carrier with a selec¬tive targeting potential also seems to be a very promising way for improving stability as well as selectivity. Despite all the advances, developing homogeneous inorganic polymers with narrow molecular weight distributions is a multidis¬ciplinary challenge. The current keynote speech provides a review of the opportunities and challenges of using inor¬ganic polymers as drug carriers.

Engineering peptide drug therapeutics through chemical conjugation and implication in clinics.

The development of peptide drugs has made tremendous progress in the past few decades because of the advancements in modification chemistry and analytical technologies. The novel-designed peptide drugs have been modified through various biochemical methods with improved diagnostic, therapeutic, and drug-delivery strategies. Researchers found it a helping hand to overcome the inherent limitations of peptides and bring continued advancements in their applications. Furthermore, the emergence of peptide-drug conjugates (PDCs)-utilizes target-oriented peptide moieties as a vehicle for cytotoxic payloads via conjugation with cleavable chemical agents, resulting in the key foundation of the new era of targeted peptide drugs. This review summarizes the various classifications of peptide drugs, suitable chemical modification strategies to improve the ADME (adsorption, distribution, metabolism, and excretion) features of peptide drugs, and recent (2015-early 2024) progress/achievements in peptide-based drug delivery systems as well as their fruitful implication in preclinical and clinical studies. Furthermore, we also summarized the brief description of other types of PDCs, including peptide-MOF conjugates and peptide-UCNP conjugates. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development and progress toward a bright future of novel peptide drugs.

Preparation and characterization of azelnidipine-loaded D-α-tocopheryl polyethylene glycol succinate (TPGS) / solutol micelles

Azelnidipine is a calcium-channel antagonist classified as a “class 2” drug with high permeability and low aqueous solubility. It is used in the treatment of angina pectoris and hypertension without reflex tachycardia. Improvement of the solubility of azelnidipine and increasing drug’s bioavailability can be achieved through the drug encapsulation in solutol / D-α-tocopheryl polyethylene glycol succinate (TPGS) micelles. Six formulas were prepared by direct disso¬lution after using different amounts of solutol and TPGS. TPGS and solutol act as solubilizers, permeation enhancers, and P-glycoprotein inhibitors. The particle size, particle size distribution, zeta potential, and entrapment efficiency were determined. Depending on particle size and entrapment efficiency, formula #6 was selected and subjected to in vitro dilution stability and in vitro release studies. The results obtained showed that formula #6 was the best formula, with a high entrapment efficiency percentage equal to 86.5%±0.58% and a small particle size equal to 21.9±7.75 nm that did not change significantly after dilution up to 100-fold; a fact that reveals the high thermodynamic and kinetic stability of the optimum formula. The formula #6 release profile showed a controlled release of the drug from micelles when compared to plain drug release. Based on these results, polymeric nanomicelles are regarded as a promising delivery system for azelnidipine.

Microemulsions based on Acer truncatum seed oil and its fatty acids: fabrication, rheological property, and stability

Aims To construct the microemulsion delivery system (ME) loading ATSO and NA and study their physicochemical characteristics to enhance their stability and water solubility. Methods By plotting ternary phase diagrams, the composition and proportions of the MEs were determined. The physicochemical characteristics and stability of MEs were evaluated by mean diameter, polydispersity index (PDI), pH, electrical conductivity, transmission electron microscopy (TEM), rheological behaviour measurement, and phase inversion temperature (PIT). Results The MEs was composed with EL-40 as a surfactant and specifically with the addition of ethanol as a cosurfactant in NA-loaded ME. The mean diameters of ATSO-loaded ME and NA-loaded ME were 39.65 ± 0.24 nm and 32.90 ± 2.65 nm, and PDI were 0.49 ± 0.01 and 0.28 ± 0.14, respectively. The TEM confirmed the spherical and smooth morphology of MEs. The rheological results indicated that MEs are dilatant fluids with the advantages of low viscosity, high fluidity, and tolerance to temperature fluctuations. The mean diameter and PDI of MEs showed no significant change after storage at 25 °C for 28 days and centrifugation. Conclusion The prepared microemulsions could expand the application prospects of ATSO and NA products in cosmetics, medicine, foods and other fields.

Logic-Based Strategy for Spatiotemporal Release of Dual Extracellular Vesicles in Osteoarthritis Treatment.

To effectively treat osteoarthritis (OA), the existing inflammation must be reduced before the cartilage damage can be repaired; this cannot be achieved with a single type of extracellular vesicles (EVs). Here, a hydrogel complex with logic-gates function is proposed that can spatiotemporally controlled release two types of EVs: interleukin 10 (IL-10)+ EVs to promote M2 polarization of macrophage, and SRY-box transcription factor 9 (SOX9)+ EVs to increase cartilage matrix synthesis. Following dose-of-action screening, the dual EVs are loaded into a matrix metalloporoteinase 13 (MMP13)-sensitive self-assembled peptide hydrogel (KM13E) and polyethylene glycol diacrylate/gelatin methacryloyl-hydrogel microspheres (PGE), respectively. These materials are mixed to form a "microspheres-in-gel" KM13E@PGE system. In vitro, KM13E@PGE abruptly released IL-10+ EVs after 3 days and slowly released SOX9+ EVs for more than 30 days. In vivo, KM13E@PGE increased the CD206+ M2 macrophage proportion in the synovial tissue and decreased the tumor necrosis factor-α and IL-1β levels. The aggrecan and SOX9 expressions in the cartilage tissues are significantly elevated following inflammation subsidence. This performance is not achieved using anti-inflammatory or cartilage repair therapy alone. The present study provides an injectable, integrated delivery system with spatiotemporal control release of dual EVs, and may inspire logic-gates strategies for OA treatment.