scholarly journals Combined Method to Remove Endotoxins from Protein Nanocages for Drug Delivery Applications: The Case of Human Ferritin

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 229
Author(s):  
Filippo Silva ◽  
Leopoldo Sitia ◽  
Raffaele Allevi ◽  
Arianna Bonizzi ◽  
Marta Sevieri ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Biological Fluids ◽  
Affinity Purification ◽  
Delivery Systems ◽  
Point Of View ◽  
Uniform Structure ◽  
Structure Stability ◽  
Target Cells ◽  
Clinical Phase ◽  
Main Challenge

Protein nanocages represent an emerging candidate among nanoscaled delivery systems. Indeed, they display unique features that proved to be very interesting from the nanotechnological point of view such as uniform structure, stability in biological fluids, suitability for surface modification to insert targeting moieties and loading with different drugs and dyes. However, one of the main concerns regards the production as recombinant proteins in E. coli, which leads to a product with high endotoxin contamination, resulting in nanocage immunogenicity and pyrogenicity. Indeed, a main challenge in the development of protein-based nanoparticles is finding effective procedures to remove endotoxins without affecting protein stability, since every intravenous injectable formulation that should be assessed in preclinical and clinical phase studies should display endotoxins concentration below the admitted limit of 5 EU/kg. Different strategies could be employed to achieve such a result, either by using affinity chromatography or detergents. However, these strategies are not applicable to protein nanocages as such and require implementations. Here we propose a combined protocol to remove bacterial endotoxins from nanocages of human H-ferritin, which is one of the most studied and most promising protein-based drug delivery systems. This protocol couples the affinity purification with the Endotrap HD resin to a treatment with Triton X-114. Exploiting this protocol, we were able to obtain excellent levels of purity maintaining good protein recovery rates, without affecting nanocage interactions with target cells. Indeed, binding assay and confocal microscopy experiments confirm that purified H-ferritin retains its capability to specifically recognize cancer cells. This procedure allowed to obtain injectable formulations, which is preliminary to move to a clinical trial.

scholarly journals Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 640 ◽  
Author(s):  
Jihye Yoo ◽  
Changhee Park ◽  
Gawon Yi ◽  
Donghyun Lee ◽  
Heebeom Koo
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Small Molecules ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Active Targeting ◽  
Target Cells ◽  
Specific Receptors ◽  
Nanoparticle Drug Delivery

Targeting nanoparticle (NP) carriers to sites of disease is critical for their successful use as drug delivery systems. Along with optimization of physicochemical properties, researchers have focused on surface modification of NPs with biological ligands. Such ligands can bind specific receptors on the surface of target cells. Furthermore, biological ligands can facilitate uptake of modified NPs, which is referred to as ‘active targeting’ of NPs. In this review, we discuss recent applications of biological ligands including proteins, polysaccharides, aptamers, peptides, and small molecules for NP-mediated drug delivery. We prioritized studies that have demonstrated targeting in animals over in vitro studies. We expect that this review will assist biomedical researchers working with NPs for drug delivery and imaging.

scholarly journals UNDERSTANDING NOVEL POLYMER AND LIPID BASED CARRIER SYSTEMS IN CLINICIAN PERSPECTIVE

2020 ◽  
Vol 4 (10) ◽  
Author(s):  
Kallem Sharat Venkat Reddy
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Drug Dosage ◽  
Delivery Systems ◽  
Review Article ◽  
Point Of View ◽  
Smart Polymers ◽  
The Past ◽  
Novel Drug ◽  
Carrier Systems

From the past two decades, technological advancements in science and chemistry made possible many new drug delivery systems that have the potential to completely change the course of routine therapeutic ways.  Lipid and polymer-based drug delivery systems are considered to be the pillars of many drug dosage forms, irrespective of their route of administration. With increasing knowledge on their chemistry, lipids and polymers are being modified and used as potential novel drug delivery systems with smart polymers and lipid nanotechnology paving the way for efficient drug delivery into the patient. This review article covers the swing of these drug delivery systems in the current market and interpreting all this from a health care professional’s point of view. Keywords: Gene delivery, Lipid based drug delivery, Polymer based drug delivery, Target specific drugs, Solid lipid nanoparticles

scholarly journals Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5294 ◽  
Author(s):  
Yana Zorkina ◽  
Olga Abramova ◽  
Valeriya Ushakova ◽  
Anna Morozova ◽  
Eugene Zubkov ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Drug Delivery ◽  
Alzheimer's Disease ◽  
Drug Delivery Systems ◽  
Neuropsychiatric Disorders ◽  
Delivery Systems ◽  
Target Cells ◽  
Advantages And Disadvantages ◽  
Experimental Drugs ◽  
Neuropsychiatric Diseases

Neuropsychiatric diseases are one of the main causes of disability, affecting millions of people. Various drugs are used for its treatment, although no effective therapy has been found yet. The blood brain barrier (BBB) significantly complicates drugs delivery to the target cells in the brain tissues. One of the problem-solving methods is the usage of nanocontainer systems. In this review we summarized the data about nanoparticles drug delivery systems and their application for the treatment of neuropsychiatric disorders. Firstly, we described and characterized types of nanocarriers: inorganic nanoparticles, polymeric and lipid nanocarriers, their advantages and disadvantages. We discussed ways to interact with nerve tissue and methods of BBB penetration. We provided a summary of nanotechnology-based pharmacotherapy of schizophrenia, bipolar disorder, depression, anxiety disorder and Alzheimer’s disease, where development of nanocontainer drugs derives the most active. We described various experimental drugs for the treatment of Alzheimer’s disease that include vector nanocontainers targeted on β-amyloid or tau-protein. Integrally, nanoparticles can substantially improve the drug delivery as its implication can increase BBB permeability, the pharmacodynamics and bioavailability of applied drugs. Thus, nanotechnology is anticipated to overcome the limitations of existing pharmacotherapy of psychiatric disorders and to effectively combine various treatment modalities in that direction.

The application of aluminium phthalocyanine AlPs-4-mediated photodynamic therapy against human soft tissue sarcoma (RMS) cell line

2020 ◽  
pp. A-R
Author(s):  
Muhammad Zakir ◽  
Ahmat Khurshid ◽  
Muhammad Iqbal Khan ◽  
Asma Khattak ◽  
Murad Ali Khan
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Iron Oxide ◽  
Cobalt Ferrite ◽  
Combined Treatment ◽  
In Vivo Studies ◽  
Individual Treatment ◽  
Target Cells ◽  
Photodynamic Effect ◽  
Main Challenge

The main challenge in the cancer treatment is the on-target drug delivery to the affected cells. Various therapies have been designed to target the affected cells efficiently but still the success is awaited. An iron and cobalt nanocomposite for the effective drug delivery to target cells was designed. The photodynamic effect of anticancer drugs loaded with iron oxide and cobalt ferrite nanomaterials coated with polyvinyl alcohol (PVA) was studied. The iron oxide nanoparticles (IONPs) and cobalt ferrite (CF) NPs without the loaded drugs were characterized by UV, XRD, FTIR, SEM and EDX techniques. The photodynamic effect of the photosensitizer, doxorubicin, and dacarbazine loaded nanomaterials were screened against human rhabdomyosarcoma (RMS) cells after incubation for 3 h, 24 h, and 48 h using MTT assay. The combination of photodynamic therapy (PDT) with chemo drugs is studied over different doses. When RMS cells were exposed to nanomaterials loaded with chemo drugs and PDT alone, it resulted in less cell killing compared to chemo drugs followed by PDT. These results revealed that in the case of combined treatment (combination therapy) the cell viability decreases as compared to individual treatment (monotherapy). The in vitro studies showed positive results which give a new pathway for the in vivo studies.

scholarly journals Understanding the Factors Influencing Chitosan-Based Nanoparticles-Protein Corona Interaction and Drug Delivery Applications

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4758
Author(s):  
Cristina Moraru ◽  
Manuela Mincea ◽  
Gheorghita Menghiu ◽  
Vasile Ostafe
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Biological Fluids ◽  
Chemical Properties ◽  
Protein Corona ◽  
Target Cells ◽  
Major Application ◽  
Targeted Drug ◽  
Drug Delivery Applications

Chitosan is a polymer that is extensively used to prepare nanoparticles (NPs) with tailored properties for applications in many fields of human activities. Among them, targeted drug delivery, especially when cancer therapy is the main interest, is a major application of chitosan-based NPs. Due to its positive charges, chitosan is used to produce the core of the NPs or to cover NPs made from other types of polymers, both strategies aiming to protect the carried drug until NPs reach the target sites and to facilitate the uptake and drug delivery into these cells. A major challenge in the design of these chitosan-based NPs is the formation of a protein corona (PC) upon contact with biological fluids. The composition of the PC can, to some extent, be modulated depending on the size, shape, electrical charge and hydrophobic/hydrophilic characteristics of the NPs. According to the composition of the biological fluids that have to be crossed during the journey of the drug-loaded NPs towards the target cells, the surface of these particles can be changed by covering their core with various types of polymers or with functionalized polymers carrying some special molecules, that will preferentially adsorb some proteins in their PC. The PC’s composition may change by continuous processes of adsorption and desorption, depending on the affinity of these proteins for the chemical structure of the surface of NPs. Beside these, in designing the targeted drug delivery NPs one can take into account their toxicity, initiation of an immune response, participation (enhancement or inhibition) in certain metabolic pathways or chemical processes like reactive oxygen species, type of endocytosis of target cells, and many others. There are cases in which these processes seem to require antagonistic properties of nanoparticles. Products that show good behavior in cell cultures may lead to poor in vivo results, when the composition of the formed PC is totally different. This paper reviews the physico-chemical properties, cellular uptake and drug delivery applications of chitosan-based nanoparticles, specifying the factors that contribute to the success of the targeted drug delivery. Furthermore, we highlight the role of the protein corona formed around the NP in its intercellular fate.

Macromolecular engineering and stimulus response in the design of advanced drug delivery systems

MRS Bulletin ◽  
2010 ◽  
Vol 35 (9) ◽  
pp. 665-672 ◽  
Author(s):  
Christine Jérôme
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Colloidal Particles ◽  
Polymeric Micelles ◽  
Complex Structure ◽  
Delivery Systems ◽  
Target Cells ◽  
Amphiphilic Copolymers ◽  
Stimuli Responsive ◽  
Research Activity

Extensive research activity is currently devoted to controlled drug delivery systems, mainly as nano-sized particles. Although biocompatible and (bio)degradable polymers play a key role in this field, their shaping into colloidal particles (e.g., polymeric micelles and nanoparticles) usually requires the proper design of amphiphilic copolymers as effective stabilizers. Strategies for synthesizing these copolymers that preserve the intrinsic properties of the constitutive polymers are discussed in this article. Synthesis of amphiphilic copolymers with a more complex structure and endowed with functionality is also considered, with the purpose of enhancing the performance of the nanocarriers. The focus is increasingly on nanocarriers of the third generation, which resist coalescence and elimination by the immune system, and which are readily incorporated into chosen target cells. The more recent quest is for smart nanocarriers that exhibit the additional capacity of being stimuli-responsive.

scholarly journals Erythrocytes and Nanoparticles: New Therapeutic Systems

2021 ◽  
Vol 11 (5) ◽  
pp. 2173
Author(s):  
Clara Guido ◽  
Gabriele Maiorano ◽  
Carmen Gutiérrez-Millán ◽  
Barbara Cortese ◽  
Adriana Trapani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Hybrid Approach ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Target Cells ◽  
Preparation Methods ◽  
Medical Practitioners ◽  
Surface Receptors ◽  
Wide Range

Nano-delivery systems represent one of the most studied fields, thanks to the associated improvement in the treatment of human diseases. The functionality of nanostructures is a crucial point, which the effectiveness of nanodrugs depends on. A hybrid approach strategy using synthetic nanoparticles (NPs) and erythrocytes offers an optimal blend of natural and synthetic materials. This, in turn, allows medical practitioners to exploit the combined advantages of erythrocytes and NPs. Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, as well as the long circulation time allowed by specific surface receptors that inhibit immune clearance. In this review, we will discuss several methods—whole erythrocytes as drug carriers, red blood cell membrane-camouflaged nanoparticles and nano-erythrosomes (NERs)—while paying attention to their application and specific preparation methods. The ability to target cells makes erythrocytes excellent drug delivery systems. They can carry a wide range of therapeutic molecules while also acting as bioreactors; thus, they have many applications in therapy and in the diagnosis of many diseases.

Novel biomarker and drug delivery systems for theranostics – extracellular vesicles

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ewa Ł. Stępień ◽  
Carina Rząca ◽  
Paweł Moskal
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Biological Fluids ◽  
Cell Types ◽  
Biological Properties ◽  
Delivery Systems ◽  
Cell Uptake ◽  
Positron Emission ◽  
Composition Structure

Abstract Extracellular vesicles (EVs) are nano- and micro-sized double-layered membrane entities derived from most cell types and released into biological fluids. Biological properties (cell-uptake, biocompatibility), and chemical (composition, structure) or physical (size, density) characteristics make EVs a good candidate for drug delivery systems (DDS). Recent advances in the field of EVs (e.g., scaling-up production, purification) and developments of new imaging methods (total-body positron emission tomography [PET]) revealed benefits of radiolabeled EVs in diagnostic and interventional medicine as a potential DDs in theranostics.

scholarly journals Transporter-Targeted Nano-Sized Vehicles for Enhanced and Site-Specific Drug Delivery

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2837 ◽  
Author(s):  
Longfa Kou ◽  
Qing Yao ◽  
Hailin Zhang ◽  
Maoping Chu ◽  
Yangzom D. Bhutia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plasma Membrane ◽  
Blood Brain Barrier ◽  
Drug Delivery Systems ◽  
Cell Types ◽  
Delivery Systems ◽  
Target Cells ◽  
Specific Cell ◽  
Site Specific ◽  
Nano Drug Delivery

Nano-devices are recognized as increasingly attractive to deliver therapeutics to target cells. The specificity of this approach can be improved by modifying the surface of the delivery vehicles such that they are recognized by the target cells. In the past, cell-surface receptors were exploited for this purpose, but plasma membrane transporters also hold similar potential. Selective transporters are often highly expressed in biological barriers (e.g., intestinal barrier, blood–brain barrier, and blood–retinal barrier) in a site-specific manner, and play a key role in the vectorial transfer of nutrients. Similarly, selective transporters are also overexpressed in the plasma membrane of specific cell types under pathological states to meet the biological needs demanded by such conditions. Nano-drug delivery systems could be strategically modified to make them recognizable by these transporters to enhance the transfer of drugs across the biological barriers or to selectively expose specific cell types to therapeutic drugs. Here, we provide a comprehensive review and detailed evaluation of the recent advances in the field of transporter-targeted nano-drug delivery systems. We specifically focus on areas related to intestinal absorption, transfer across blood–brain barrier, tumor-cell selective targeting, ocular drug delivery, identification of the transporters appropriate for this purpose, and details of the rationale for the approach.

scholarly journals A REVIEW ON CURRENT STATUS OF SELF-EMULSIFYING DRUG DELIVERY SYSTEMS

2019 ◽  
Vol 3 (7) ◽  
Author(s):  
R. Nagaraju ◽  
Damineni Saritha ◽  
P. Subhash Chandra Bose ◽  
G. Ravi ◽  
Valluru Ravi
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Aqueous Solubility ◽  
Delivery Systems ◽  
Current Status ◽  
Hydrophobic Drugs ◽  
Related Information ◽  
Main Challenge ◽  
Drug Compounds ◽  
Gentle Agitation

The modern drug delivery system of hydrophobic drugs presents a main challenge because of the poor aqueous solubility of such compounds. Self emulsifying drug delivery systems (SEDDS) are usually used to enhance the bioavailability of hydrophobic drugs. SEDDS can be administered orally in soft or hard gelatin capsules and form fine relatively stable oil in water (o/w) emulsions upon aqueous dilution due to the gentle agitation of the gastrointestinal fluids. From time to time so many workers have claimed different rational applications of Self-emulsifying formulation for increcing bioavailability and site-specific targeting of highly lipophilic drugs. Significant improvement in the oral bioavailability of these drug compounds has been demonstrated for each case. The fact that almost 40% of the new drug compounds are hydrophobic in nature implies that studies with SEDDS will continue, and more drug compounds formulated as SEDDS will reach the pharmaceutical market in the future. The present article gives an overview of the Composition, mechanism, advantages, disadvantages, characterization, recent advancements, patents related information of SEEDS and commercial products approved for oral transmucosal administration.

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