scholarly journals Milk Exosomes: Perspective Agents for Anticancer Drug Delivery

2020 ◽  
Vol 21 (18) ◽  
pp. 6646
Author(s):  
Sergey Sedykh ◽  
Anna Kuleshova ◽  
Georgy Nevinsky
Keyword(s):  
Targeted Delivery ◽  
Oral Delivery ◽  
Biological Fluid ◽  
Chemotherapeutic Agents ◽  
Biologically Active ◽  
Synthesis Methods ◽  
Anticancer Drug Delivery ◽  
New Therapeutic Approaches ◽  
Urgent Task ◽  
Biological Compatibility

Exosomes are biological nanovesicles that participate in intercellular communication by transferring biologically active chemical compounds (proteins, microRNA, mRNA, DNA, and others). Due to their small size (diameter 40–100 nm) and high biological compatibility, exosomes are promising delivery tools in personalized therapy. Because artificial exosome synthesis methods are not developed yet, the urgent task is to develop an effective and safe way to obtain exosomes from natural sources. Milk is the only exosome-containing biological fluid that is commercially available. In this regard, milk exosomes are unique and promising candidates for new therapeutic approaches to treating various diseases, including cancer. The appearance of side effects during the use of cytotoxic and cytostatic agents is among the main problems in cancer chemotherapy. According to this, the targeted delivery of chemotherapeutic agents can be a potential solution to the toxic effect of chemotherapy. The ability of milk exosomes to carry out biologically active substances to the cell makes them promising tools for oral delivery of chemotherapeutic agents. This review is devoted to the methods of milk exosome isolation, their biological components, and prospects for their use in cancer treatment.

scholarly journals Plant-Derived Anticancer Compounds as New Perspectives in Drug Discovery and Alternative Therapy

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1109
Author(s):  
Cristina Adriana Dehelean ◽  
Iasmina Marcovici ◽  
Codruta Soica ◽  
Marius Mioc ◽  
Dorina Coricovac ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Alternative Therapy ◽  
Natural Compounds ◽  
Mechanisms Of Action ◽  
Chemotherapeutic Agents ◽  
Biologically Active ◽  
Bioactive Molecules ◽  
Multi Drug Resistance ◽  
Chemopreventive Agents ◽  
Pharmaceutical Agents

Despite the recent advances in the field of chemically synthetized pharmaceutical agents, nature remains the main supplier of bioactive molecules. The research of natural products is a valuable approach for the discovery and development of novel biologically active compounds possessing unique structures and mechanisms of action. Although their use belongs to the traditional treatment regimes, plant-derived compounds still cover a large portion of the current-day pharmaceutical agents. Their medical importance is well recognized in the field of oncology, especially as an alternative to the limitations of conventional chemotherapy (severe side effects and inefficacy due to the occurrence of multi-drug resistance). This review offers a comprehensive perspective of the first blockbuster chemotherapeutic agents of natural origin’s (e.g. taxol, vincristine, doxorubicin) mechanism of action using 3D representation. In addition is portrayed the step-by-step evolution from preclinical to clinical evaluation of the most recently studied natural compounds with potent antitumor activity (e.g. resveratrol, curcumin, betulinic acid, etc.) in terms of anticancer mechanisms of action and the possible indications as chemotherapeutic or chemopreventive agents and sensitizers. Finally, this review describes several efficient platforms for the encapsulation and targeted delivery of natural compounds in cancer treatment

HORSE MILK EXOSOMES – PERSCEPTIVE AGENTS FOR TARGET DELIVERY

2020 ◽  
pp. 77-78
Author(s):  
A. Kuleshova ◽  
G. Nevinsky
Keyword(s):  
Targeted Delivery ◽  
Therapeutic Potential ◽  
Biological Fluid ◽  
Prion Diseases ◽  
Biologically Active ◽  
Many Body ◽  
Active Components ◽  
Target Delivery ◽  
Non Invasive ◽  
Unique Source

Exosomes are extracellular vesicles with a diameter of 40-100 nm. Exosomes are found in many body fluids, including milk. Milk is a unique source of exosomes since the collection of this biological fluid is non-invasive, and animals can produce several liters of milk per day. Cow's milk cannot be used to isolate biologically active components with therapeutic potential due to the risk of transmission of prion diseases. In this regard, horse milk is a unique source of exosomes that can be used for targeted delivery.

scholarly journals In VitroCharacterization of Pluronic F127 and D--Tocopheryl Polyethylene Glycol 1000 Succinate Mixed Micelles as Nanocarriers for Targeted Anticancer-Drug Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Adeel Masood Butt ◽  
Mohd Cairul Iqbal Mohd Amin ◽  
Haliza Katas ◽  
Narong Sarisuta ◽  
Wasu Witoonsaridsilp ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Polyethylene Glycol ◽  
Anticancer Drug ◽  
Targeted Delivery ◽  
Mixed Micelles ◽  
Chemotherapeutic Agents ◽  
Pluronic F127 ◽  
Breast Adenocarcinoma ◽  
Anticancer Drug Delivery ◽  
Polyethylene Glycol 1000

Mixed micelles of Pluronic F127 andD-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) in different molar ratios (10 : 0, 7 : 3, 5 : 5, and 3 : 7) were prepared to characterize this system as nanocarriers for targeted delivery of chemotherapeutic agents. Their size, zeta potential, critical micelle concentration, drug loading content, entrapment efficiency, drug release, cytotoxicity, and stability in serum were evaluatedin vitroby using doxorubicin as the model anticancer drug. The micellar sizes ranged from 25 to 35 nm. The 7 : 3 and 5 : 5 micellar combinations had lower critical micelle concentrations ( M) than the 10 : 0 combination ( M). The entrapment efficiencies of the 7 : 3, 5 : 5, and 3 : 7 micellar combinations were 72%, 88%, and 69%, respectively. Doxorubicin release was greater at acidic tumour pH than at normal physiological pH. The doxorubicin-loaded mixed micelles showed greater percent inhibition and apoptosis activity in human breast adenocarcinoma (MCF-7) and acute monocytic leukaemia (THP-1) cell lines than free doxorubicin did. The mixed micelles were also stable against aggregation and precipitation in serum. These findings suggest that Pluronic F127-TPGS mixed micelles could be used as nanocarriers for targeted anticancer-drug delivery.

Seeds as Economical Production Platform for Recombinant Proteins

2020 ◽  
Vol 27 (2) ◽  
pp. 89-104 ◽  
Author(s):  
Muhammad Sarwar Khan ◽  
Faiz Ahmad Joyia ◽  
Ghulam Mustafa
Keyword(s):  
Oral Delivery ◽  
High Protein ◽  
Biologically Active ◽  
Cold Chain ◽  
Protein Accumulation ◽  
Long Term Storage ◽  
Production Platform ◽  
Vaccine Antigens ◽  
Term Storage

: The cost-effective production of high-quality and biologically active recombinant molecules especially proteins is extremely desirable. Seed-based recombinant protein production platforms are considered as superior choice owing to lack of human/animal pathogenic organisms, lack of cold chain requirements for transportation and long-term storage, easy scalability and development of edible biopharmaceuticals in plants with objective to be used in purified or partially processed form is desirable. This review article summarizes the exceptional features of seed-based biopharming and highlights the needs of exploiting it for commercial purposes. Plant seeds offer a perfect production platform for high-value molecules of industrial as well as therapeutic nature owing to lower water contents, high protein storage capacity, weak protease activity and long-term storage ability at ambient temperature. Exploiting extraordinarily high protein accumulation potential, vaccine antigens, antibodies and other therapeutic proteins can be stored without effecting their stability and functionality up to years in seeds. Moreover, ability of direct oral consumption and post-harvest stabilizing effect of seeds offer unique feature of oral delivery of pharmaceutical proteins and vaccine antigens for immunization and disease treatment through mucosal as well as oral route.

Enhancing the Therapeutic Efficacy of Bortezomib in Cancer Therapy Using Polymeric Nanostructures

2020 ◽  
Vol 25 (46) ◽  
pp. 4883-4892 ◽  
Author(s):  
Mitra Korani ◽  
Shahla Korani ◽  
Elham Zendehdel ◽  
Amin Reza Nikpoor ◽  
Mahmoud Reza Jaafari ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Therapeutic Option ◽  
Nuclear Factor Κb ◽  
Chemotherapeutic Agents ◽  
26S Proteasome ◽  
Reversible Inhibitor ◽  
Pharmacokinetic Parameters ◽  
Nanoparticle Delivery ◽  
High Doses ◽  
Nfκb Pathway

: Bortezomib (VELCADE®) is a boronate peptide and first-in-class proteasome inhibitor serving an important role in degenerating several intracellular proteins. It is a reversible inhibitor of the 26S proteasome, with antitumor activity and antiproliferative properties. This agent principally exerts its antineoplastic effects by inhibiting key players in the nuclear factor κB (NFκB) pathway involved in cell proliferation, apoptosis, and angiogenesis. This medication is used in the management of multiple myeloma. However, more recently, it has been used as a therapeutic option for mantle cell lymphoma. While promising, bortezomib has limited clinical applications due to its adverse effects (e.g., hematotoxicity and peripheral neuropathy) and low effectiveness in solid tumors resulting from its poor penetration into such masses and suboptimal pharmacokinetic parameters. Other limitations to bortezomib include its low chemical stability and bioavailability, which can be overcome by using nanoparticles for its delivery. Nanoparticle delivery systems can facilitate the targeted delivery of chemotherapeutic agents in high doses to the target site, while sparing healthy tissues. Therefore, this drug delivery system has provided a solution to circumvent the limitations faced with the delivery of traditional cancer chemotherapeutic agents. Our aim in this review was to describe polymer-based nanocarriers that can be used for the delivery of bortezomib in cancer chemotherapy.

scholarly journals Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 369
Author(s):  
Jennifer Schwestka ◽  
Eva Stoger
Keyword(s):  
Targeted Delivery ◽  
Oral Delivery ◽  
Protective Coatings ◽  
Production Costs ◽  
Cell Wall Proteins ◽  
Production Host ◽  
And Storage ◽  
Harsh Conditions ◽  
Encapsulation Methods

The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules.

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

scholarly journals Intracellular and Extracellular Expression of Bacillus thuringiensis Crystal Protein Cry5B in Lactococcus lactis for Use as an Anthelminthic

2015 ◽  
Vol 82 (4) ◽  
pp. 1286-1294 ◽  
Author(s):  
Evelyn Durmaz ◽  
Yan Hu ◽  
Raffi V. Aroian ◽  
Todd R. Klaenhammer
Keyword(s):  
Bacillus Thuringiensis ◽  
Lactococcus Lactis ◽  
Copy Number ◽  
Oral Delivery ◽  
Membrane Integrity ◽  
Biologically Active ◽  
High Copy Number ◽  
Cry Protein ◽  
Western Blots ◽  
Content Type

ABSTRACTTheBacillus thuringiensiscrystal (Cry) protein Cry5B (140 kDa) and a truncated version of the protein, tCry5B (79 kDa), are lethal to nematodes. Genes encoding the two proteins were separately cloned into a high-copy-number vector with a strong constitutive promoter (pTRK593) inLactococcus lactisfor potential oral delivery against parasitic nematode infections. Western blots using a Cry5B-specific antibody revealed that constitutively expressed Cry5B and tCry5B were present in both cells and supernatants. To increase production,cry5Bwas cloned into the high-copy-number plasmid pMSP3535H3, carrying a nisin-inducible promoter. Immunoblotting revealed that 3 h after nisin induction, intracellular Cry5B was strongly induced at 200 ng/ml nisin, without adversely affecting cell viability or cell membrane integrity. Both Cry5B genes were also cloned into plasmid pTRK1061, carrying a promoter and encoding a transcriptional activator that invoke low-level expression of prophage holin and lysin genes inLactococcuslysogens, resulting in a leaky phenotype. Cry5B and tCry5B were actively expressed in the lysogenic strainL. lactisKP1 and released into cell supernatants without affecting culture growth. Lactate dehydrogenase (LDH) assays indicated that Cry5B, but not LDH, leaked from the bacteria. Lastly, using intracellular lysates fromL. lactiscultures expressing both Cry5B and tCry5B,in vivochallenges ofCaenorhabditis elegansworms demonstrated that the Cry proteins were biologically active. Taken together, these results indicate that active Cry5B proteins can be expressed intracellularly in and released extracellularly fromL. lactis, showing potential for future use as an anthelminthic that could be delivered orally in a food-grade microbe.

scholarly journals Onco-Receptors Targeting in Lung Cancer via Application of Surface-Modified and Hybrid Nanoparticles: A Cross-Disciplinary Review

Processes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 621
Author(s):  
Fakhara Sabir ◽  
Maimoona Qindeel ◽  
Mahira Zeeshan ◽  
Qurrat Ul Ain ◽  
Abbas Rahdar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Targeted Delivery ◽  
Current Knowledge ◽  
Folate Receptor ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
The Body ◽  
Hybrid Nanoparticles ◽  
Wide Range ◽  
Surface Modified

Lung cancer is among the most prevalent and leading causes of death worldwide. The major reason for high mortality is the late diagnosis of the disease, and in most cases, lung cancer is diagnosed at fourth stage in which the cancer has metastasized to almost all vital organs. The other reason for higher mortality is the uptake of the chemotherapeutic agents by the healthy cells, which in turn increases the chances of cytotoxicity to the healthy body cells. The complex pathophysiology of lung cancer provides various pathways to target the cancerous cells. In this regard, upregulated onco-receptors on the cell surface of tumor including epidermal growth factor receptor (EGFR), integrins, transferrin receptor (TFR), folate receptor (FR), cluster of differentiation 44 (CD44) receptor, etc. could be exploited for the inhibition of pathways and tumor-specific drug targeting. Further, cancer borne immunological targets like T-lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and dendritic cells could serve as a target site to modulate tumor activity through targeting various surface-expressed receptors or interfering with immune cell-specific pathways. Hence, novel approaches are required for both the diagnosis and treatment of lung cancers. In this context, several researchers have employed various targeted delivery approaches to overcome the problems allied with the conventional diagnosis of and therapy methods used against lung cancer. Nanoparticles are cell nonspecific in biological systems, and may cause unwanted deleterious effects in the body. Therefore, nanodrug delivery systems (NDDSs) need further advancement to overcome the problem of toxicity in the treatment of lung cancer. Moreover, the route of nanomedicines’ delivery to lungs plays a vital role in localizing the drug concentration to target the lung cancer. Surface-modified nanoparticles and hybrid nanoparticles have a wide range of applications in the field of theranostics. This cross-disciplinary review summarizes the current knowledge of the pathways implicated in the different classes of lung cancer with an emphasis on the clinical implications of the increasing number of actionable molecular targets. Furthermore, it focuses specifically on the significance and emerging role of surface functionalized and hybrid nanomaterials as drug delivery systems through citing recent examples targeted at lung cancer treatment.

The importance of linkers in the structure of PSMA ligands

2021 ◽  
Vol 28 ◽  
Author(s):  
Anastasia A. Uspenskaya ◽  
Ekaterina A. Nimenko ◽  
Aleksei E. Machulkin ◽  
Elena K. Beloglazkina ◽  
Alexander G. Majouga
Keyword(s):  
Prostate Cancer ◽  
Solid Phase ◽  
Biologically Active ◽  
Modern World ◽  
Synthesis Methods ◽  
Amino Acid Residues ◽  
Ongoing Research ◽  
Phase Synthesis ◽  
Diagnose Prostate Cancer ◽  
Positive Effect

: Cancer is one of the leading social problems of the modern world. Today prostate cancer is the second leading cause of cancer deaths among men. Targeted drug delivery is widely used to treat and diagnose prostate cancer. Conjugates selectively binding to prostate specific membrane antigen based on urea ligands are being actively developed against this disease. The linker has a significant influence on the biological activity of such conjugates. The linker performs a large number of functions, and its modification is one of the key methods of creating the best pharmacological profile. This review aims to discuss and analyze the main approaches to the method of introduction and synthesis of linkers for this type of conjugates without a description of the influence of biologically active molecules, as well as to establish the key modification methods that have a significant role on the structure-activity relationship. For this purpose, a review of the current scientific literature was performed, both for the conjugates under development and for those already undergoing clinical trials. It was found that the optimal structure is a linker containing an aliphatic fragment near the vector-molecule (n(CH2) = 3-6), followed by a polypeptide chain consisting of 2 to 4 amino acid residues. The presence of a Phe-Phe dipeptide chain or the introduction of negatively charged groups also has a positive effect. Ongoing research in this field helps to establish the accurate effect of each linker fragment, and the development of solid-phase synthesis methods makes it much easier to achieve this goal.

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