Type Of Delivery Vehicle Research Articles

Protein Expression Correlates Linearly with mRNA Dose over Up to Five Orders of Magnitude In Vitro and In Vivo.

Messenger RNA is rapidly gaining significance as a therapeutic modality. Here, we address the dependence of dose–response functions on the type of delivery vehicle, cell line, and incubation time. Knowledge of these characteristics is crucial for the application of mRNA. As delivery vehicles, a lipid-based formulation and the cell-penetrating peptide Pepfect14 (PF14) were employed. As cell lines, we included a glomerular endothelial cell line (mGEnC) as a model for differentiated cells, HeLa cells, and SKOV-3 ovarian carcinoma cells. Uptake and expression were detected by flow cytometry, using a Cy5-labelled mRNA coding for enhanced green fluorescent protein (EGFP). There was a linear correlation of dose, uptake, and expression, and this correlation was maintained for over up to 72 h. Through application of a multistep kinetic model, we show that differences in expression levels can already be explained by the number of mRNAs packaged per delivery vehicle. Using luciferase as a reporter protein, linearity of expression was observed over 5 orders of magnitude in vitro and 3 orders of magnitude in vivo. Overall, the results demonstrate that mRNA provides excellent quantitative control over protein expression, also over extended periods of time.

Clustering for Item Delivery Using Rule-K-Means

In this paper, we introduce an alternative approach as model for cluster analysis. The data were analyzed by rule-k-means algorithm. It's combine between k-means algorithm and rules. As an application, we use the simulate of item delivery data to classify items based on destination addresses. The goal is to map the item based on type of delivery vehicle. The clustering can be used as a recommendation to the item delivery service company.

Unlockable Nanocomplexes with Self-Accelerating Nucleic Acid Release for Effective Staged Gene Therapy of Cardiovascular Diseases.

Nucleic acid (NA)-based therapy is proposed to address serious diseases such as cardiovascular diseases (CVDs). Powerful NA delivery vehicles are essential for effective gene therapy. Herein, a novel type of delivery vehicle, an unlockable core-shell nanocomplex (Hep@PGEA) with self-accelerating NA release, is structurally designed. Hep@PGEA is composed of disulfide-bridged heparin nanoparticle (HepNP) core and low-toxicity PGEA cationic shell. In comparison with NA, heparin, a negatively charged polysaccharide macromolecule, exhibits stronger interactions with cationic species. Upon the breakdown of redox-responsive HepNP cores, unlocked heparin would interact with the outer cationic shells and replace the condensed NA to facilitate NA release. Such unique Hep@PGEA is successfully explored for effective miRNA-pDNA staged gene therapy of myocardial infarction (MI), one of the most serious CVDs. With the progression of MI, glutathione amounts in heart tissues increase. MiR-499 (for the inhibition of cardiomyocyte apoptosis) and plasmid encoding vascular endothelial growth factor (for the promotion of angiogenesis) are sequentially delivered for systemic treatment of MI. Such treatment produces impressive results in restoring heart function and suppressing cardiac hypertrophy. Due to the wide existence of redox agents in cells, the proposed unlockable delivery nanovehicle and staged therapy strategy can provide new methods to effectively treat different serious diseases.

Evaluation of in vitro anti-inflammatory effects of crude ginger and rosemary extracts obtained through supercritical CO2 extraction on macrophage and tumor cell line: the influence of vehicle type.

BackgroundNumerous plants from have been investigated due to their anti-inflammatory activity and, among then, extracts or components of ginger (Zingiber officinale Roscoe) and rosemary (Rosmarinus officinalis L.), sources of polyphenolic compounds. 6-gingerol from ginger rhizome and carnosic acid and carnosol from rosemary leaves present anti-tumor, anti-inflammatory and antioxidant activities. However, the evaluation of the mechanisms of action of these and other plant extracts is limited due to their high hydrophobicity. Dimethylsulfoxide (DMSO) is commonly used as a vehicle of liposoluble materials to mammalian cells in vitro, presenting enhanced cell penetration. Liposomes are also able to efficiently deliver agents to mammalian cells, being capable to incorporate in their structure not only hydrophobic molecules, but also hydrophilic and amphiphilic compounds. Another strategy is based on the use of Pluronic F-68, a biocompatible low-foaming, non-ionic surfactant, to disperse hydrophobic components. Here, these three delivery approaches were compared to analyze their influence on the in vitro anti-inflammatory effects of ginger and rosemary extracts, at different concentrations, on primary mammalian cells and on a tumor cell line.MethodsGinger and rosemary extracts free of organic solvents were obtained by supercritical fluid extraction and dispersed in DMSO, Pluronic F-68 or liposomes, in variable concentrations. Cell viability, production of inflammatory mediators and nitric oxide (NO) release were measured in vitro on J774 cell line and murine macrophages primary culture stimulated with bacterial lipopolysaccharide and interferon-γ after being exposed or not to these extracts.ResultsGinger and rosemary extracts obtained by supercritical CO2 extraction inhibited the production of pro-inflammatory cytokines and the release of NO by peritoneal macrophages and J774 cells. The delivery vehicles influenced the anti-inflammatory effects. Comparatively, the ginger extract showed the highest anti-inflammatory activity on the tumor cell line. Controversially, rosemary extract dispersed on DMSO induced a more significant IL-1 and TNF-α reduction than ginger extract in primary macrophages.ConclusionsAmongst the tested delivery vehicles, DMSO was the most suitable, presenting reduced cytotoxicity, followed by Pluronic F-68 and liposomes, provably due to differences in their form of absorption, distribution and cellular metabolism. Co-administration of liposomes and plant extracts may cause death of macrophages cells and induction of NO production. It can be concluded that some of the beneficial effects attributed to extracts of ginger and rosemary may be associated with the inhibition of inflammatory mediators due to their high antioxidant activity. However, these effects were influenced by the type of delivery vehicle.

Ferritin Nanocages: Great Potential as Clinically Translatable Drug Delivery Vehicles?

Conventional therapeutics are commonly associ­ ated with high lipophilicity and poor pharmaco­ kinetics. In tumor therapy, these issues often lead to off­target damage to normal tissues. In the ongoing quest to improve treatment specific­ ity, nanotechnology has proven to be a powerful tool. With large surface areas and easy meth­ ods of surface modification, it is possible to use nanoparticles as carriers to load and transport drug molecules to tumors with great efficiency and accuracy [1,2]. Many types of nanopar­ ticles – made of metals, metal oxides, carbon nanotubes, polymers or liposomes – have been proposed and tested as drug carriers [2]. Among them, synthetic polymers and liposomes have been the most studied. Despite the myriad of for­ mulations investigated, however, only a minimal number have made it to clinical trials. Regard­ ing polymer nanoparticles, the most widely used are poly(lactic acid) and poly(glycolic acid), and their copolymer poly(lactide­co­glycolide) [3]. Most other polymers are associated with toxic­ ity, biodegradability or immunogenicity, which prevents their clinical use. More recently, proteins have emerged as a novel type of delivery vehicle. As a natural polymer, proteins raise fewer biocompatibility concerns. This gives them an edge from the per­ spective of clinical translation. A good example is albumin­based drug delivery, which is play­ ing an increasingly important role in clinics. Currently, a methotrexate–albumin conjugate, an albumin­binding prodrug of doxorubicin (DOX) and an albumin paclitaxel nanoparticle (Abraxane) have been clinically evaluated. Abraxane in particular is recognized as one of the first nanoparticle­based drugs approved for use by the US FDA. This success has inspired researchers to seek other protein­based nanocarriers.

An efficient cell-targeting and intracellular controlled-release drug delivery system based on MSN-PEM-aptamer conjugates

The current work demonstrates an efficient cell-targeting and intracellular controlled-release drug delivery system based on a MSN-PEM-aptamer conjugate. In this system, mesoporous silica nanoparticles (MSN) were employed as drug containers for their high surface area and high loading efficacy. Polyelectrolyte multilayers (PEM) were used to prevent the premature leakage of drugs during the delivery process and controllably released drugs under reducing conditions. Finally, a cancer cell-specific DNA aptamer was selected as the targeting recognition molecule for its high cell recognition. By taking the advantages of high payload, stimuli-response to intracellular environment and high cell recognition ability, this type of delivery vehicle could be used as a promising drug delivery system for specific intracellular delivery and may offer much needed efficacy in cancer therapy.