scholarly journals Antitumor vector systems based on bioactive lectin of Bacillus subtilis ІМВ B-7724

2021 ◽  
Vol 12 (3) ◽  
pp. 190-200
Author(s):  
A. L. Petranovska ◽  
◽  
A. P. Kusyak ◽  
N. M. Korniichuk ◽  
S. P. Turanska ◽  
...  

Сombination of properties of lectins and magnetically sensitive iron-containing nanocomposites (NC) for use in oncology is actual and promising from scientific and applied point of view. The aim of the research is to synthesize and to study new iron-containing NC and magnetic fluids containing bioactive bacterial lectin, promising for use as prototypes of new effective antitumor vector systems for targeted drug delivery and combined local therapy of cancer with minimized side effects on the body and improved compatibility with other remedies. To create vector systems, nanodisperse magnetite was synthesized by the Elmore reaction. The synthesis of aluminum-containing coating on the surface of Fe3O4 was carried out by double chemical modification with aluminum isopropylate. The obtained Fe3O4/Al2O3 NC was impregnated with sucrose solutions. Carbonization of the carbohydrate shell of NC was carried out in argon (500 °C). As a result, Fe3O4/Al2O3/C NC was obtained. The magnetic properties of nanostructures were measured using a laboratory vibration magnetometer of Foner type at room temperature. Adsorption immobilization of lectin was performed in 0.9 % NaCl solution in a dynamic mode at room temperature. Bacterial cytotoxic lectin of B. subtilis IMB B-7724 was used in the experiments. The amount of adsorbed substance (A) on the surface of nanocomposites was determined by measuring the concentration of lectin in the contact solutions before and after adsorption using a calibration graph. Measuring of the optical density and absorption spectra of lectin was performed on a spectrometer Lambda 35 UV/vis Perkin Elmer Instruments at λ = 280 nm. Standard techniques and equipment were used for biological research. The processes of adsorption immobilization of cytotoxic bacterial lectin of B. subtilis IMB B-7724 from physiologic saline on the surface of magnetite and carbon-containing Fe3O4/Al2O3/C NC were studied at room temperature. It has been found that the adsorption capacity of lectin on the surface of magnetite is 25.3 mg/g, and Fe3O4/Al2O3/C NC – 36.3 mg/g (at initial concentrations of lectin 0.06–0.4 mg/mL). The extraction extent of lectin R (%) was 12–38 % for magnetite and 46–67 % for Fe3O4/Al2O3/C NC. The dependence of the adsorption capacity on time was studied. A magnetic fluid (MF) based on single-domain Fe3O4, containing lectin was synthesized and investigated. Immobilization of lectin on MF particles was carried out in a dynamic mode at room temperature for 3 hours. The concentration of lectin in the composition of MF was 0.2 mg/mL. MF with immobilized lectin was further modified with PEG-2000. The synthesis of Fe3O4/ol.Na/lectin/PEG (ol.Na – sodium oleate) vector system was carried out in a dynamic mode for 3 hours. Modification of the surface of nanoparticles with polyethylene glycol was performed in order to increase the stability of the magnetic fluid, reducing the aggregation of particles. To determine the effect of experimental samples on the viability of MCF-7 cells in vitro, the following samples were prepared: Fe3O4/ol.Na/PEG (MF), CFe3O4 = 3 mg/mL; cytotoxic lectin of B. subtilis IMB B-7724 (CL), CCL = 0.2 mg/mL; nanobiocomposite (NBC). Nanobiocomposite based on MF and bacterial lectin was found to have a synergistic cytotoxic effect on MCF-7 human breast cancer cells, causing up to 40 % cell death. The IC50 values for the nanobiocomposite and lectin in relation to MCF-7 cells were 100 and 125 μg/mL, respectively. The results of research show that the combination of properties of lectins and magnetically sensitive iron-containing NC for use in oncology is a promising direction in creating new effective antitumor vector systems for targeted drug delivery and combined local therapy of cancer. The use of natural components in vector systems is a way to minimize the side effects on the body and improve compatibility with other antitumor remedies.

Author(s):  
Diksha Sharma ◽  
Abhishek Sharma

  The drug delivery system has been advanced to release the drug according to the body requirement during the entire period of treatment and also for the delivery at the targeted site. Several novel drug delivery systems have emerged encompassing different route of administration to achieve controlled and targeted drug delivery, magnetic microsphere carrier being one of them. Magnetic microsphere is an alternative to traditional radiation methods. As the traditional radiation methods use highly penetrating radiation that is absorbed throughout the body and cause side effects hence its use is limited. Therefore, a safe and effective alternate is needed like magnetic microsphere. The excessive circulating drug particles are minimized by this delivery system. Moreover, the aim of specific targeting is to enhance the effectiveness of drug delivery and at the same time to lessen the toxicity and side effects. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials that are used for magnetic microsphere are chitosan, dextran, etc. One of the most utilized magnetic microspheres is serum albumine whether from human or other suitable animals. Drug release from the albumin microsphere can be controlled by various stabilization procedures. Overall, the targeted magnetic microsphere is much valuable novel drug delivery system for what more work have to be done. By knowing the importance of all this, the present paper reviews the mechanism, preparation, and applications of magnetic microspheres. As the targeted drug delivery system implies selective and effective localization of drug into the target at therapeutic concentrations with limited access to non-target sites. Magnetic microspheres hold great promises for reaching the goal of controlled and site-specific drug delivery.


Author(s):  
Elahe Darvishi ◽  
Mahsa Minadi ◽  
Somayeh Mirsadeghi ◽  
Behrang Shiri

Introduction: Much research has been carried out to improve drug delivery and targeted drug delivery to the body in order to minimize side effects, provide controlled delivery of the drug to the desired location and to achieve optimal therapeutic effects. Zeolitic imidazolate-8 (ZIF-8) is a subset of MOFs that are biocompatible, stable in the aquatic environment and have adjustable porosity. In addition, at pHs 5 or 6, the bond between imidazolate-zinc ions disappears and releases the drug. In this project, ZIF-8 was used as a curcumin carrier to improve the physicochemical properties and enhance the efficacy of lipophilic drugs in the treatment of cancer. Methods: This research was a basic experimental study. ZIF-8 nanoparticles were fabricated by co-precipitation method. In addition, to prove their pH sensitivity, curcumin was first encapsulated in situ in ZIF-8 and characterized by XRD, SEM, TEM, DLS methods. Then its release was investigated at two pH of five and 7.4 saline phosphate buffer. Finally, In vitro study by MTT assay was performed on prostate cancer cell line (PC3). Data were compared by analysis of variance (ANOVA) using SPSS version 16 software. Results: After characterization of the nanoparticles by the mentioned methods, it was found that the nanoparticle dimensions were between 80-60 nm and the nanoparticle dimensions with curcumin were between 120-110 nm. In addition, in the synthesis of ZIF-8 nanoparticles, %72 of the drug was loaded, which is an acceptable amount. Conclusion: These nanoparticles showed high capacity in the treatment of prostate cancer and minimal damage to healthy cells. It can be said that using this formulation for targeted drug delivery of cancer not only reduces the side effects of anti-cancer drugs but also increases their effectiveness and can also be used to deliver low-soluble or insoluble drugs in biological environments.


2019 ◽  
Vol 15 (4) ◽  
pp. 382-397 ◽  
Author(s):  
Shashiprabha Punyakantha Dunuweera ◽  
Rajapakse Mudiyanselage Shashanka Indeevara Rajapakse ◽  
Rajapakshe Babilage Sanjitha Dilan Rajapakshe ◽  
Sudu Hakuruge Dilan Priyankara Wijekoon ◽  
Mallika Gedara Gayan Sasanka Nirodha Thilakarathna ◽  
...  

Targeted drug delivery (TDD) is an advanced and smart method of delivering drugs to the patients in a targeted sequence that increases the concentration of delivered drug only at the targeted body part of interest (organs/tissues/cells). This will in turn enhance efficacy of treatment by reducing side effects and the required dose of the drug. TDD ensures a certain defined minimally required constant amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body. This helps maintain the required plasma and tissue drug levels in the body thereby avoiding any damage to the healthy tissue via the drug. Various drug carriers that are envisaged in advanced delivery systems are soluble polymers, inorganic nanoparticles, magnetic nanoparticles, biodegradable microsphere polymers (synthetic and natural), neutrophils, fibroblasts, artificial cells, lipoproteins, liposomes, micelles and immune micelle. In selecting such a vehicle, important factors to consider are chemical and physical properties drugs, side effects or cytotoxicity to healthy cells, route to be taken for the delivery of the drug, the targeted site, and the disease. As such, TDD formulations are prepared by considering the specific properties of target cells, nature of markers or transport carriers or vehicles, which convey drug to specific receptors, and ligands and physically modulated components.


2019 ◽  
Vol 24 (44) ◽  
pp. 5296-5312 ◽  
Author(s):  
Fakhara Sabir ◽  
Rai K. Farooq ◽  
Asim.ur.Rehman ◽  
Naveed Ahmed

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc.


Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 59
Author(s):  
Abeer M. Beagan ◽  
Ahlam A. Alghamdi ◽  
Shatha S. Lahmadi ◽  
Majed A. Halwani ◽  
Mohammed S. Almeataq ◽  
...  

Currently, chemotherapy is an important method for the treatment of various cancers. Nevertheless, it has many limitations, such as poor tumour selectivity and multi-drug resistance. It is necessary to improve this treatment method by incorporating a targeted drug delivery system aimed to reduce side effects and drug resistance. The present work aims to develop pH-sensitive nanocarriers containing magnetic mesoporous silica nanoparticles (MMSNs) coated with pH-responsive polymers for tumour-targeted drug delivery via the folate receptor. 2-Diethyl amino ethyl methacrylate (DEAEMA) was successfully grafted on MMSNs via surface initiated ARGET atom transfer radical polymerization (ATRP), with an average particle size of 180 nm. The end groups of poly (2-(diethylamino)ethyl methacrylate) (PDEAEMA) brushes were converted to amines, followed by a covalent bond with folic acid (FA) as a targeting agent. FA conjugated to the nanoparticle surface was confirmed by X-ray photoelectron spectroscopy (XPS). pH-Responsive behavior of PDEAEMA brushes was investigated by Dynamic Light Scattering (DLS). The nanoparticles average diameters ranged from ca. 350 nm in basic media to ca. 650 in acidic solution. Multifunctional pH-sensitive magnetic mesoporous nanoparticles were loaded with an anti-cancer drug (Doxorubicin) to investigate their capacity and long-circulation time. In a cumulative release pattern, doxorubicin (DOX) release from nano-systems was ca. 20% when the particle exposed to acidic media, compared to ca. 5% in basic media. The nano-systems have excellent biocompatibility and are minimally toxic when exposed to MCF-7, and -MCF-7 ADR cells.


2016 ◽  
Vol 17 (1-2) ◽  
Author(s):  
Julia Modrejewski ◽  
Johanna-Gabriela Walter ◽  
Imme Kretschmer ◽  
Evren Kemal ◽  
Mark Green ◽  
...  

AbstractThe purpose of this study was to develop a model system for targeted drug delivery. This system should enable targeted drug release at a certain tissue in the body. In conventional drug delivery systems, drugs are often delivered unspecifically resulting in unwarranted adverse effects. To circumvent this problem, there is an increasing demand for the development of intelligent drug delivery systems allowing a tissue-specific mode of delivery. Within this study, nanoparticles consisting of two biocompatible polymers are used. Because of their small size, nanoparticles are well-suited for effective drug delivery. The small size affects their movement through cell and tissue barriers. Their cellular uptake is easier when compared to larger drug delivery systems. Paclitaxel was encapsulated into the nanoparticles as a model drug, and to achieve specific targeting an aptamer directed against lung cancer cells was coupled to the nanoparticles surface. Nanoparticles were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR), and nanotracking analysis (NTA). Also their surface charge was characterized from ζ-potential measurements. Their preparation was optimized and subsequently specificity of drug-loaded and aptamer-functionalized nanoparticles was investigated using lung cancer cells.


2018 ◽  
Vol 03 (02) ◽  
pp. 1840001 ◽  
Author(s):  
Fraser Stewart ◽  
Antonella Verbeni ◽  
Yongqiang Qiu ◽  
Ben F. Cox ◽  
Jan Vorstius ◽  
...  

The prevalence of gastrointestinal (GI) diseases such as Crohn’s disease, which is chronic and incurable, are increasing worldwide. Treatment often involves potent drugs with unwanted side effects. The technological–pharmacological combination of capsule endoscopy with ultrasound-mediated targeted drug delivery (UmTDD) described in this paper carries new potential for treatment of these diseases throughout the GI tract. We describe a proof-of-concept UmTDD capsule and present preliminary results to demonstrate its promise as an autonomous tool to treat GI diseases.


2019 ◽  
Vol 12 (2) ◽  
pp. 83-95 ◽  
Author(s):  
A. V. Kuroyedov ◽  
V. V. Brzhesky ◽  
E. A. Krinitsyna

Ocular targeted drug delivery is one of the most challenging tasks for pharmaceutical researchers and practical ophthalmologists. The possibilities of drug delivery to the eye are naturally determined by the anatomical structure of the eye and its physiological properties, which restrict the period when therapeutically required drug concentration could be maintained. Combined drug delivery schemes may, potentially, improve the patient’s acceptance of treatment, reduce side effects, increase efficacy, and eventually preserve vision.


Author(s):  
Маргарита Олеговна Тонкушина ◽  
Илья Дмитриевич Гагарин ◽  
Ольга Владимировна Русских ◽  
Ксения Александровна Белозерова ◽  
Александр Александрович Остроушко

Создание и использование средств адресной доставки лекарств на основе нанокластерного полиоксометаллата {MoFe} подразумевает его деструкцию в организме, сопровождающуюся постепенным высвобождением лекарства. Были определены константы скорости процесса деструкции чистого {MoFe} и в составе ассоциата с сывороточным альбумином в растворах моделирующих среду крови (фосфатный буфер с pH 7,4 и сыворотка крови крупного рогатого скота). Показана стабилизация полиоксометаллата альбумином в модельных средах. Определено соотношение компонентов в ассоциате {MoFe} -альбумин, оно составило 1,6 ионов полиоксометаллата на молекулу альбумина. The creation and use of the targeted drug delivery systems based on nanocluster polyoxometalate {MoFe} implies its destruction in the body, accompanied by the gradual release of the drug. The rate constants of the destruction of pure {MoFe} and its associate with serum albumin in solutions simulating the blood media (phosphate buffer with pH 7,4 and blood serum of cattle) were determined. The stabilization of polyoxometalate by albumin in model solutions was shown. The ratio of components in the associate {MoFe} -albumin was determined, it was 1,6 polyoxometalate ions per albumin molecule.


Author(s):  
Shyam Prasad ◽  
Vidhu Aeri ◽  
Yashwant .

The conventional drug delivery system for colonic disease may leads to absorption of drug across biological membrane of gastrointestinal tract (GIT). The absorption of drug throughout GIT may leads to increase in dose and associated side effects. Colon targeted drug delivery (CTDD) is a method of delivering medication to a patient in a manner that increases concentration of the medication in colon relative to other part of GIT. The aim of CTDD is to prolong, localize, target and have protected drug interaction to diseased tissue. The present review deals with primary as well as recent approaches of delivery of drug to colon.


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