scholarly journals Effects of Atelocollagen Formulation Containing Oligonucleotide on Endothelial Permeability

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Koji Hanai ◽  
Takashi Kojima ◽  
Mika Ota ◽  
Jun Onodera ◽  
Norimasa Sawada
Keyword(s):  
Drug Delivery ◽  
Size Structure ◽  
Biological Effects ◽  
Adherens Junction ◽  
Endothelial Permeability ◽  
Molecular Size ◽  
P38 Map Kinase ◽  
Delivery Technology ◽  
Junction Proteins

Atelocollagen is a major animal protein that is used as a highly biocompatible biomaterial. To date, atelocollagen has been used as an effective drug delivery technology to sustain the release of antitumor proteins and to enhance the antitumor activity of oligonucleotides in in vivo models. However, the biological effects of this technology are not fully understood. In the present study, we investigated the effects of atelocollagen on endothelial paracellular barrier function. An atelocollagen formulation containing oligonucleotides specifically increased the permeability of two types of endothelial cells, and the change was dependent on the molecular size, structure of the oligonucleotides used and the concentrations of the oligonucleotide and atelocollagen in the formulation. An immunohistochemical examination revealed that the formulation had effects on the cellular skeleton and intercellular structure although it did not affect the expression of adherens junction or tight junction proteins. These changes were induced through p38 MAP kinase signaling. It is important to elucidate the biological functions of atelocollagen in order to be able to exploit its drug delivery properties.

scholarly journals Drug Delivery by Ultrasound-Responsive Nanocarriers for Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1135
Author(s):  
Kristin Entzian ◽  
Achim Aigner
Keyword(s):  
Drug Delivery ◽  
Biological Effects ◽  
Invasive Technique ◽  
Stimuli Responsive ◽  
Comprehensive Overview ◽  
Drug Concentrations ◽  
Therapeutic Outcomes ◽  
Cost Efficient ◽  
Safety Considerations

Conventional cancer chemotherapies often exhibit insufficient therapeutic outcomes and dose-limiting toxicity. Therefore, there is a need for novel therapeutics and formulations with higher efficacy, improved safety, and more favorable toxicological profiles. This has promoted the development of nanomedicines, including systems for drug delivery, but also for imaging and diagnostics. Nanoparticles loaded with drugs can be designed to overcome several biological barriers to improving efficiency and reducing toxicity. In addition, stimuli-responsive nanocarriers are able to release their payload on demand at the tumor tissue site, preventing premature drug loss. This review focuses on ultrasound-triggered drug delivery by nanocarriers as a versatile, cost-efficient, non-invasive technique for improving tissue specificity and tissue penetration, and for achieving high drug concentrations at their intended site of action. It highlights aspects relevant for ultrasound-mediated drug delivery, including ultrasound parameters and resulting biological effects. Then, concepts in ultrasound-mediated drug delivery are introduced and a comprehensive overview of several types of nanoparticles used for this purpose is given. This includes an in-depth compilation of the literature on the various in vivo ultrasound-responsive drug delivery systems. Finally, toxicological and safety considerations regarding ultrasound-mediated drug delivery with nanocarriers are discussed.

scholarly journals The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology

Cartilage ◽  
2020 ◽  
pp. 194760352095939
Author(s):  
Sarah E. Mailhiot ◽  
Matthew A. Thompson ◽  
Akiko E. Eguchi ◽  
Sabrina E. Dinkel ◽  
Martin K. Lotz ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Genetic Recombination ◽  
Great Promise ◽  
Tat Protein ◽  
Binding Studies ◽  
Osteoarthritic Cartilage ◽  
Peptide Transduction ◽  
Delivery Technology

Objective Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints. Design Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both in vitro and in vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage. Results The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing in vivo genetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution. Conclusions The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.

scholarly journals A combined low-frequency electromagnetic and fluidic stimulation for a controlled drug release from superparamagnetic calcium phosphate nanoparticles: potential application for cardiovascular diseases

2018 ◽  
Vol 15 (144) ◽  
pp. 20180236 ◽  
Author(s):  
Alessandra Marrella ◽  
Michele Iafisco ◽  
Alessio Adamiano ◽  
Stefano Rossi ◽  
Maurizio Aiello ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Animal Model ◽  
Cardiovascular Diseases ◽  
Drug Release ◽  
Biological Effects ◽  
Low Frequency ◽  
Controlled Drug Release ◽  
Drug Dose

Alternative drug delivery approaches to treat cardiovascular diseases are currently under intense investigation. In this domain, the possibility to target the heart and tailor the amount of drug dose by using a combination of magnetic nanoparticles (NPs) and electromagnetic devices is a fascinating approach. Here, an electromagnetic device based on Helmholtz coils was generated for the application of low-frequency magnetic stimulations to manage drug release from biocompatible superparamagnetic Fe-hydroxyapatite NPs (FeHAs). Integrated with a fluidic circuit mimicking the flow of the cardiovascular environment, the device was efficient to trigger the release of a model drug (ibuprofen) from FeHAs as a function of the applied frequencies. Furthermore, the biological effects on the cardiac system of the identified electromagnetic exposure were assessed in vitro and in vivo by acute stimulation of isolated adult cardiomyocytes and in an animal model. The cardio-compatibility of FeHAs was also assessed in vitro and in an animal model. No alterations of cardiac electrophysiological properties were observed in both cases, providing the evidence that the combination of low-frequency magnetic stimulations and FeHAs might represent a promising strategy for controlled drug delivery to the failing heart.

scholarly journals Caffeic acid phenethyl ester (CAPE): cornerstone pharmacological studies and drug delivery systems

Pharmacia ◽  
2019 ◽  
Vol 66 (4) ◽  
pp. 223-231 ◽  
Author(s):  
Yordan Yordanov
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Biological Effects ◽  
Caffeic Acid Phenethyl Ester ◽  
Delivery Systems ◽  
Large Contribution ◽  
Current Review ◽  
Pharmacological Studies

Propolis is a natural product with a plethora of biological effects, utilized by traditional medicine since antiquity. However, its application as a pharmaceutical is hindered by its variable composition and difficult standardization. CAPE has been shown to be a major component of propolis, with a large contribution to its pharmacological effects, among which the anti-inflammatory, antioxidant and antineoplastic have been attracting most attention. The current review article aims to present the cornerstone pharmacological studies of CAPE throughout the years, following its discovery, which confirmed its primary importance among propolis constituents and opened the path to its intensive research as a potential pharmaceutical. We present the diversity of drug delivery systems of CAPE, which have been developed to improve its efficacy in in vitro and in vivo disease models and discuss their primary promises and weaknesses. The increased interest in recent years over more practical approaches of CAPE research such as its pharmaceutical formulation comes to show that it has a potential to become commercialized as a pharmaceutical.

Secretion of adipokines by human adipose tissue in vivo: partitioning between capillary and lymphatic transport

2011 ◽  
Vol 301 (4) ◽  
pp. E659-E667 ◽  
Author(s):  
Norman E. Miller ◽  
C. Charles Michel ◽  
M. Nazeem Nanjee ◽  
Waldemar L. Olszewski ◽  
Irina P. Miller ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Biological Effects ◽  
Molecular Size ◽  
Human Adipose Tissue ◽  
Lymphatic Transport ◽  
Peripheral Lymph ◽  
Total Transport ◽  
Secretion Rates ◽  
Molecular Radius

Peptides secreted by adipose tissue (adipokines) may enter blood via capillaries or lymph. The relative importance of these pathways for a given adipokine might influence its biological effects. Because this has not been studied in any species, we measured the concentrations of seven adipokines and eight nonsecreted proteins in afferent peripheral lymph and venous plasma from 12 healthy men. Data for nonsecreted proteins were used to derive indices of microvascular permeability, which in conjunction with the molecular radii of the adipokines were used to estimate the amounts leaving the tissue via capillaries. Transport rates via lymph were estimated from the lymph adipokine concentrations and lymph flow rates and total transport (secretion) as the sum of this and capillary transport. Concentrations of nonsecreted proteins were always lower in lymph than in plasma. With the exception of adiponectin, adipokine concentrations were always higher in lymph ( P < 0.01). Leptin and MCP-1 were secreted at the highest rates (means: 43 μg/h or 2.7 nmol/h and 32 μg/h or 2.4 nmol/h, respectively). IL-6 and MCP-1 secretion rates varied greatly between subjects. The proportion of an adipokine transported via lymph was directly related to its molecular radius ( r s = +0.94, P = 0.025, n = 6), increasing from 14 to 100% as the radius increased from 1.18 (IL-8) to 3.24 nm (TNFα). We conclude that the lymph/capillary partitioning of adipokines is a function of molecular size, which may affect both their regional and systemic effects in vivo. This finding may have implications for the physiology of peptides secreted by other tissues.

scholarly journals Submicron-Sized Nanocomposite Magnetic-Sensitive Carriers: Controllable Organ Distribution and Biological Effects

Polymers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1082 ◽  
Author(s):  
Marina V. Novoselova ◽  
Sergey V. German ◽  
Olga A. Sindeeva ◽  
Oleg A. Kulikov ◽  
Olga V. Minaeva ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Drug Delivery ◽  
Magnetite Nanoparticles ◽  
Biological Effects ◽  
Magnetic Field Gradient ◽  
Organ Distribution ◽  
Mri Imaging ◽  
Lack Of Information ◽  
The Given

Although new drug delivery systems have been intensely developed in the past decade, no significant increase in the efficiency of drug delivery by nanostructure carriers has been achieved. The reasons are the lack of information about acute toxicity, the influence of the submicron size of the carrier and difficulties with the study of biodistribution in vivo. Here we propose, for the first time in vivo, new nanocomposite submicron carriers made of bovine serum albumin (BSA) and tannic acid (TA) and containing magnetite nanoparticles with sufficient content for navigation in a magnetic field gradient on mice. We examined the efficacy of these submicron carriers as a delivery vehicle in combination with magnetite nanoparticles which were systemically administered intravenously. In addition, the systemic toxicity of this carrier for intravenous administration was explicitly studied. The results showed that (BSA/TA) carriers in the given doses were hemocompatible and didn’t cause any adverse effect on the respiratory system, kidney or liver functions. A combination of gradient-magnetic-field controllable biodistribution of submicron carriers with fluorescence tomography/MRI imaging in vivo provides a new opportunity to improve drug delivery efficiency.

scholarly journals Molecular targeting of renal inflammation using drug delivery technology to inhibit NF-κB improves renal recovery in chronic kidney disease

2020 ◽  
Vol 319 (1) ◽  
pp. F139-F148
Author(s):  
Alejandro R. Chade ◽  
Maxx L. Williams ◽  
Jason E. Engel ◽  
Erika Williams ◽  
Gene L. Bidwell
Keyword(s):  
Drug Delivery ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Renal Recovery ◽  
Swine Model ◽  
Monocyte Chemoattractant Protein 1 ◽  
Delivery Technology

Inflammation is a major determinant for the progression of chronic kidney disease (CKD). NF-κB is a master transcription factor upregulated in CKD that promotes inflammation and regulates apoptosis and vascular remodeling. We aimed to modulate this pathway for CKD therapy in a swine model of CKD using a peptide inhibitor of the NF-κB p50 subunit (p50i) fused to a protein carrier [elastin-like polypeptide (ELP)] and equipped with a cell-penetrating peptide (SynB1). We hypothesized that intrarenal SynB1-ELP-p50i therapy would inhibit NF-κB-driven inflammation and induce renal recovery. CKD was induced in 14 pigs. After 6 wk, pigs received single intrarenal SynB1-ELP-p50i therapy (10 mg/kg) or placebo ( n = 7 each). Renal hemodynamics were quantified in vivo using multidetector computed tomography before and 8 wk after treatment. Pigs were then euthanized. Ex vivo experiments were performed to quantify renal activation of NF-κB, expression of downstream mediators of NF-κB signaling, renal microvascular density, inflammation, and fibrosis. Fourteen weeks of CKD stimulated NF-κB signaling and downstream mediators (e.g., TNF-α, monocyte chemoattractant protein-1, and IL-6) accompanying loss of renal function, inflammation, fibrosis, and microvascular rarefaction versus controls. All of these were improved after SynB1-ELP-p50i therapy, accompanied by reduced circulating inflammatory cytokines as well, which were evident up to 8 wk after treatment. Current treatments for CKD are largely ineffective. Our study shows the feasibility of a new treatment to induce renal recovery by offsetting inflammation at a molecular level. It also supports the therapeutic potential of targeted inhibition of the NF-κB pathway using novel drug delivery technology in a translational model of CKD.

scholarly journals Functionality and Acceptance of the EsoCap System—A Novel Film-Based Drug Delivery Technology: Results of an In Vivo Study

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 828
Author(s):  
Christoph Rosenbaum ◽  
Michael Grimm ◽  
Julius Krause ◽  
Adrian Rump ◽  
Rebecca Kessler ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Polymer Film ◽  
Esophageal Mucosa ◽  
Esophageal Diseases ◽  
System A ◽  
Mri Scans ◽  
Novel Drug ◽  
First Time ◽  
Delivery Technology

There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called EsoCap system, by 12 healthy volunteers. For the first time, the EsoCap system enables targeted placement on the esophageal mucosa of a mucoadhesive polymer film. Acceptance was determined by means of a standardized questionnaire after administration and functionality of the device by MRI scans. Two different setups of the EsoCap system were tested: one setup with a density of 0.4 g/cm3 and one with a density of 1.0 g/cm3. Acceptability of the dosage form was also confirmed in addition to functionality, by measuring the applied film length. It was found that acceptance of the variant with the higher density was significantly better. This novel drug delivery technology could enable a targeted, local and long-lasting therapy of the esophagus for the first time, depending on the polymer film used.

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