Technology insight: plant-derived vesicles—how far from the clinical biotherapeutics and therapeutic drug carriers?

: Exosomes are a heterogeneous group of nano-sized natural membrane vesicles released from various cells and exist in body fluids. Different from the previous understanding of the function of exosomes as “garbage bins”, exosomes act as carriers with many kinds of bioactive molecules (e.g., proteins, lipids, and nucleic acids) to play an important role in cell-cell communication. Growing evidence in recent years has suggested that exosomes also play some roles in the pathogenesis, diagnosis, and treatment modalities of some brain diseases, including ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis, and brain cancers. Exosomes as therapeutic drug carriers for brain drug delivery have received extensive attention as well as exosomes can overcome the blood-brain barrier (BBB). However, the low targeting ability and size-dependent cellular uptake of native exosomes could profoundly affect the delivery performance of exosomes. Recent studies have indicated that engineered exosomes can increase the drug uptake efficiency and the subsequent drug efficacy. In the present paper, we will briefly introduce the engineering methods and applications of engineered exosomes in the treatment of brain diseases, and then focus on discussing the advantages and challenges of exosome-based drug delivery platforms to further enrich and boost the development of exosomes as a promising drug delivery strategy for brain diseases.

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Regulation of the Ocular Cell/Tissue Response by Implantable Biomaterials and Drug Delivery Systems

Bioengineering ◽

10.3390/bioengineering7030065 ◽

2020 ◽

Vol 7 (3) ◽

pp. 65 ◽

Cited By ~ 1

Author(s):

Francesco Baino ◽

Saeid Kargozar

Keyword(s):

Drug Delivery ◽

Drug Release ◽

Drug Delivery Systems ◽

Drug Carriers ◽

Delivery Systems ◽

Tissue Response ◽

Ocular Tissue ◽

Therapeutic Drug ◽

Tissue Cell ◽

Target Tissue

Therapeutic advancements in the treatment of various ocular diseases is often linked to the development of efficient drug delivery systems (DDSs), which would allow a sustained release while maintaining therapeutic drug levels in the target tissues. In this way, ocular tissue/cell response can be properly modulated and designed in order to produce a therapeutic effect. An ideal ocular DDS should encapsulate and release the appropriate drug concentration to the target tissue (therapeutic but non-toxic level) while preserving drug functionality. Furthermore, a constant release is usually preferred, keeping the initial burst to a minimum. Different materials are used, modified, and combined in order to achieve a sustained drug release in both the anterior and posterior segments of the eye. After giving a picture of the different strategies adopted for ocular drug release, this review article provides an overview of the biomaterials that are used as drug carriers in the eye, including micro- and nanospheres, liposomes, hydrogels, and multi-material implants; the advantages and limitations of these DDSs are discussed in reference to the major ocular applications.

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New Supramolecular Drug Carriers: The Study of Organogel Conjugated Gold Nanoparticles

Molecules ◽

10.3390/molecules26247462 ◽

2021 ◽

Vol 26 (24) ◽

pp. 7462

Author(s):

Joanna Kowalczuk ◽

Andrzej Łapiński ◽

Elżbieta Stolarczyk ◽

Oleg M. Demchuk ◽

Konrad Kubiński ◽

...

Keyword(s):

Gold Nanoparticles ◽

Sodium Citrate ◽

Drug Carriers ◽

Point Of View ◽

Therapeutic Drug ◽

Distribution Profile ◽

Release Process ◽

Biological Assays ◽

The Matrix ◽

Solvent Molecules

An aqueous solution of sodium citrate stabilized gold nanoparticles (AuNP) in the presence of N-lauroyl-L-alanine (C12ALA) forms a stable gel. The structure of the gel and the distribution profile of AuNP in it were analyzed. Will nanoparticles separated from each other with sodium citrate behave in the same way in solution and trapped in the gel matrix? Will the spatial limitation of solvent molecules aggregate nanoparticles and destroy their homogeneity? These questions are very important from the point of view of the use of gold nanoparticles, trapped in the gel structure as carriers of drugs in the slow-release process. The lack of homogeneity of this distribution will have a major impact on the rate of release of the appropriate amount of therapeutic drug from the matrix. In this work, we attempt to answer these questions. The performed biological assays revealed that both C12ALA and C12ALA-AuNP show an excellent level of biological neutrality. They might be used as a transporting medium for a drug delivery without affecting the drug’s activity.

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Tubulin structure at intermediate resolution

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140634 ◽

1995 ◽

Vol 53 ◽

pp. 852-853

Author(s):

K. H. Downing ◽

S. G. Wolf ◽

E. Nogales

Keyword(s):

High Resolution ◽

Structural Data ◽

Therapeutic Drug ◽

Zinc Ions ◽

Two Dimensional ◽

X Ray Diffraction ◽

X Ray ◽

Negative Stain ◽

Functional Mechanisms ◽

Tubulin Structure

Microtubules are involved in a host of critical cell activities, many of which involve transport of organelles through the cell. Different sets of microtubules appear to form during the cell cycle for different functions. Knowledge of the structure of tubulin will be necessary in order to understand the various functional mechanisms of microtubule assemble, disassembly, and interaction with other molecules, but tubulin has so far resisted crystallization for x-ray diffraction studies. Fortuitously, in the presence of zinc ions, tubulin also forms two-dimensional, crystalline sheets that are ideally suited for study by electron microscopy. We have refined procedures for forming the sheets and preparing them for EM, and have been able to obtain high-resolution structural data that sheds light on the formation and stabilization of microtubules, and even the interaction with a therapeutic drug.Tubulin sheets had been extensively studied in negative stain, demonstrating that the same protofilament structure was formed in the sheets and microtubules. For high resolution studies, we have found that the sheets embedded in either glucose or tannin diffract to around 3 Å.

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Diagnose und Monitoring bei chronisch-entzündlicher Darmerkrankung

Therapeutische Umschau ◽

10.1024/0040-5930/a001002 ◽

2018 ◽

Vol 75 (5) ◽

pp. 316-328

Author(s):

Christian Ansprenger ◽

Emanuel Burri

Keyword(s):

Therapeutic Drug Monitoring ◽

Drug Monitoring ◽

Morbus Crohn ◽

Therapeutic Drug ◽

Körperliche Untersuchung

Zusammenfassung. Die Diagnose und auch die Überwachung von chronisch entzündlichen Darmerkrankungen ruht auf mehreren Säulen: Anamnese, körperliche Untersuchung, Laborwerte (im Blut und Stuhl), Endoskopie, Histologie und Bildgebung. Die Diagnose kann nicht anhand eines einzelnen Befundes gestellt werden. In den letzten Jahren hat sich das Therapieziel weg von klinischen Endpunkten hin zu endoskopischen und sogar histologischen Endpunkten entwickelt. Für einige dieser neuen Therapieziele existiert allerdings noch keine allgemein gültige Definition. Regelmässige Endoskopien werden von Patienten schlecht toleriert, weshalb Surrogat-Marker wie Calprotectin untersucht wurden und eine gute Korrelation mit der mukosalen Entzündungsaktivität nachgewiesen werden konnte. Entsprechend zeigte sich bei Morbus Crohn eine Algorithmus-basierte Therapiesteuerung – unter anderem basierend auf Calprotectin – einer konventionellen Therapiesteuerung überlegen. Die Überwachung der medikamentösen Therapie («Therapeutic Drug Monitoring» [TDM]) ist ein zweites Standbein des Monitoring von chronisch entzündlichen Darmerkrankungen. Mit zunehmendem Einsatz vor allem der Biologika-Therapien wurden sowohl reaktives TDM (in Patienten mit klinischem Rezidiv) als auch proaktives TDM (in Patienten in Remission / stabiler Erkrankung) untersucht und haben (teilweise) Eingang in aktuelle Richtlinien gefunden. Zukünftige Studien werden die vorgeschlagenen Therapieziele besser definieren und den Nutzen der medikamentösen Therapieüberwachung auf den Krankheitsverlauf weiter untersuchen müssen.

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