scholarly journals Novel Approaches for Efficient Delivery of Tyrosine Kinase Inhibitors

2019 ◽  
Vol 22 ◽  
pp. 37-48 ◽  
Author(s):  
Zahra Moradpour ◽  
Leila Barghi
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Dissolution Rate ◽  
Targeted Delivery ◽  
Kinase Inhibitors ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Amorphous Solid Dispersion ◽  
Crystal Modification ◽  
Particle Size Reduction

Epidermal growth factor receptors (EGFRs) have potential to be considered as therapeutic target for cancer treatment especially in cancer patients with overexpression of EGFR. Cetuximab as a first monoclonal antibody and Imatinib as the first small molecule tyrosine kinase inhibitor (SMTKI) were approved by FDA in 1998 and 2001. About 28 SMTKIs have been approved until 2015 and a large number of compound with kinase inhibitory activity are at the different phases of clinical trials. Although Kinase inhibitors target specific intracellular pathways, their tissue or cellular distribution are not specific. So treatment with these drugs causes serious dose dependent side effects. Targeted delivery of kinase inhibitors via dendrimers, polymeric nanoparticles, magnetic nanoparticles and lipid based delivery systems such as liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) can lead to reduction of side effects and improving therapeutic efficacy of the drugs in the target organs. Furthermore formulation of these drugs is challenged by their physicochemical properties such as solubility and dissolution rate. The main approaches in order to increase dissolution rate, are particle size reduction, self-emulsification, cyclodextrin complexation, crystal modification and amorphous solid dispersion. Synergistic therapeutic effect, decreased side effects and drug resistant, reduced cost and increased patient compliance are the advantages associated with using combination therapy especially in the treatment of cancer. Combination of TKIs with chemotherapeutic agents or biopharmaceuticals such as monoclonal antibodies and oligonucleotides and also combination of two TKIs within one formulation is possible by new targeting delivery systems. This article reviews the recent advances in the design and development of delivery systems for TKIs.

scholarly journals CELL CARRIERS AS SYSTEMS OF DELIVERY OF ANTITUMOR DRUGS (REVIEW)

2019 ◽  
Vol 8 (1) ◽  
pp. 43-57
Author(s):  
O. V. Trineeva ◽  
A. J. Halahakoon ◽  
A. I. Slivkin
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Chemotherapeutic Agents ◽  
Pharmaceutical Chemistry ◽  
Scientific Publications ◽  
Actual Problem ◽  
Low Efficiency

Introduction. Drug delivery systems are defined as systems that deliver the optimal amount of a drug to a target target, increase the effectiveness of treatment, and reduce adverse effects. Regulation of the rate of release of drugs and bringing to specific tissues where active ingredients are needed are the main objectives of drug delivery systems. The development of systems for targeted, organ-specific and controlled delivery of medicinal, prophylactic and diagnostic agents is currently a relevant area of research for pharmacy and medicine. Of particular interest is the actual problem of increasing the frequency of manifestations of side effects of drugs. The side effect of drugs, their low efficiency is often explained by the inaccessibility of drugs directly to the target. Text. Currently, targeted delivery of chemotherapeutic agents and drug delivery systems has completely changed the tactics and approaches in the drug treatment of cancer, allowing to reduce the side effects of the drug and generally increase the effectiveness of the course of treatment. This paper summarizes and systematizes information about targeted systems for drug delivery of antitumor activity, described in the scientific literature and used in pharmacy and medicine. Most of the methods for obtaining cellular forms of toxic drugs discussed in this review are still at the development stage, and some methods are gradually finding practical application abroad in medicine and other fields. Vincristine (VCR) and vinblastine (VBL) are the most widely used and effective drugs in chemotherapeutic practice. Despite their effectiveness against various oncological diseases, there are a number of harmful side effects that limit the widespread use of these drugs. Conclusion. There is the possibility of using cellular carriers as a VCR and VBL delivery system. In scientific publications, there is still no data on the use of cellular carriers for encapsulating VCR and VBL. Therefore, relevant studies are devoted to the possibility of using cellular carriers to reduce side effects, improve efficiency, and develop dosage forms for the delivery of VCR and VBL to pathological foci. This topic is currently being actively developed by members of the Department of Pharmaceutical Chemistry and Pharmaceutical Technology, Pharmaceutical Faculty, Voronezh State University.

Side effects of tyrosine kinase inhibitors (TKIs) on bone remodelling

2012 ◽  
Vol 224 (03) ◽  
Author(s):  
JT Tauer ◽  
A Ulmer ◽  
LC Hofbauer ◽  
M Suttorp
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Bone Remodelling

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.

A Review on Formulation and Development of Solid Self-Nano Emulsifying Drug Delivery Systems

2021 ◽  
Vol 14 (4) ◽  
pp. 5519-5228
Author(s):  
Sunitha M Reddy ◽  
Sravani Baskarla
Keyword(s):  
Drug Delivery ◽  
Dissolution Rate ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Delivery Systems ◽  
Water Solubility ◽  
Drug Loading ◽  
Aqueous Solubility ◽  
Delivery Systems ◽  
Particle Size Reduction

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.  

scholarly journals Nilotinib therapy in an imatinib intolerant chronic myeloid leukemia patient with pulmonary severe hypertension

2015 ◽  
Vol 4 (2S) ◽  
pp. 17-20
Author(s):  
Mario Annunziata
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Chronic Phase ◽  
Chronic Myeloid Leukemia Patient ◽  
Cytogenetic Response ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Cutaneous Rash

Imatinib mesylate is a tyrosine kinase inhibitor that has significant efficacy in the treatment of chronic myelogenous leukemia. In general, hematologic and extrahematologic side effects of imatinib therapy are mild to moderate, with the large majority of patients tolerating prolonged periods of therapy. However, a minority of patients are completely intolerant of therapy, while others are able to remain on therapy despite significant side effects. Here, we describe a chronic phase CML patient with pulmonary arterial hypertension, mechanical hearth valve, who experienced extrahematologic adverse event (persistent grade III cutaneous rash, despite two discontinuations of imatinib and using of steroid). Necessitating switch to one of new tyrosine kinase inhibitors, nilotinib, has resulted in complete cytogenetic response and major molecular response, after 3 and 6 months, respectively. No cross-intolerance with imatinib was observed during nilotinib therapy. Besides, this clinical case suggests that warfarin and nilotinib can be used concurrently without the risk of increased anticoagulant effect.

Dual-sensitive dual-prodrug nanoparticles with light-controlled endo/lysosomal escape for synergistic photoactivated chemotherapy

2021 ◽  
Author(s):  
Yubin Huang ◽  
Hongtong Lu ◽  
Shasha He ◽  
Qingfei Zhang ◽  
Xiaoyuan Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Clinical Application ◽  
Drug Delivery Systems ◽  
Controlled Drug Delivery ◽  
Delivery Systems ◽  
Chemotherapeutic Agents

The clinical application of conventional chemotherapeutic agents, represented by cisplatin, is limited by severe side effects. So, it is essential to explore more safer and controlled drug delivery systems for...

scholarly journals Hypocalcemia induced by tyrosine kinase inhibitors: targeted treatment with ‘untargeted’ side effects

2020 ◽  
Vol 59 (6) ◽  
pp. 726-729 ◽  
Author(s):  
Annika M. A. Berends ◽  
Anouk N. A. van der Horst-Schrivers ◽  
Sjoukje F. Oosting ◽  
Ellen W. Kapiteijn ◽  
Jan Willem B. de Groot ◽  
...  
Keyword(s):  
Side Effects ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Targeted Treatment

scholarly journals Targeted Drug Delivery Systems for the Treatment of Glaucoma: Most Advanced Systems Review

Polymers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1742 ◽  
Author(s):  
Olga Cegielska ◽  
Paweł Sajkiewicz
Keyword(s):  
Drug Delivery ◽  
Side Effects ◽  
Targeted Delivery ◽  
Drug Targets ◽  
Drug Delivery Systems ◽  
Release Kinetics ◽  
Controlled Drug Release ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Drug Bioavailability

Each year, new glaucoma drug delivery systems are developed. Due to the chronic nature of the disease, it requires the inconvenient daily administration of medications. As a result of their elution from the eye surface and penetration to the bloodstream through undesired permeation routes, the bioavailability of active compounds is low, and systemic side effects occur. Despite numerous publications on glaucoma drug carriers of controlled drug release kinetics, only part of them consider drug permeation routes and, thus, carriers’ location, as an important factor affecting drug delivery. In this paper, we try to demonstrate the importance of the delivery proximal to glaucoma drug targets. The targeted delivery can significantly improve drug bioavailability, reduce side effects, and increase patients’ compliance compared to both commercial and scientifically developed formulations that can spread over the eye surface or stay in contact with conjunctival sac. We present a selection of glaucoma drug carriers intended to be placed on cornea or injected into the aqueous humor and that have been made by advanced materials using hi-tech forming methods, allowing for effective and convenient sustained antiglaucoma drug delivery.

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