Targeted Delivery of Radiolabeled Imaging and Therapeutic Agents: Bifunctional Radiopharmaceuticals

Author(s):  
Hideo Saji
2020 ◽  
Vol 17 (10) ◽  
pp. 911-924
Author(s):  
Rohitas Deshmukh

Colon cancer is one of the most prevalent diseases, and traditional chemotherapy has not been proven beneficial in its treatment. It ranks second in terms of mortality due to all cancers for all ages. Lack of selectivity and poor biodistribution are the biggest challenges in developing potential therapeutic agents for the treatment of colon cancer. Nanoparticles hold enormous prospects as an effective drug delivery system. The delivery systems employing the use of polymers, such as chitosan and pectin as carrier molecules, ensure the maximum absorption of the drug, reduce unwanted side effects and also offer protection to the therapeutic agent from quick clearance or degradation, thus allowing an increased amount of the drug to reach the target tissue or cells. In this systematic review of published literature, the author aimed to assess the role of chitosan and pectin as polymer-carriers in colon targeted delivery of drugs in colon cancer therapy. This review summarizes the various studies employing the use of chitosan and pectin in colon targeted drug delivery systems.


2020 ◽  
Vol 13 (4) ◽  
pp. 283-290 ◽  
Author(s):  
Vamshi Krishna Rapalli ◽  
Srividya Gorantla ◽  
Tejashree Waghule ◽  
Arisha Mahmood ◽  
Prem Prakash Singh ◽  
...  

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.


2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.


2021 ◽  
Vol 27 ◽  
Author(s):  
Bapi Gorain ◽  
Bandar E. Al-Dhubiab ◽  
Anroop Nair ◽  
Prashant Kesharwani ◽  
Manisha Pandey ◽  
...  

: The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a novel platform of advanced drug delivery with improved efficacy and safety.


Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2996
Author(s):  
Julia Y. Ljubimova ◽  
Arshia Ramesh ◽  
Liron L. Israel ◽  
Eggehard Holler

Research has increasingly focused on the delivery of high, often excessive amounts of drugs, neglecting negative aspects of the carrier’s physical preconditions and biocompatibility. Among them, little attention has been paid to “small but beautiful” design of vehicle and multiple cargo to achieve effortless targeted delivery into deep tissue. The design of small biopolymers for deep tissue targeted delivery of multiple imaging agents and therapeutics (mini-nano carriers) emphasizes linear flexible polymer platforms with a hydrodynamic diameter of 4 nm to 10 nm, geometrically favoring dynamic juxtaposition of ligands to host receptors, and economic drug content. Platforms of biodegradable, non-toxic poly(β-l-malic acid) of this size carrying multiple chemically bound, optionally nature-derived or synthetic affinity peptides and drugs for a variety of purposes are described in this review with specific examples. The size, shape, and multiple attachments to membrane sites accelerate vascular escape and fast blood clearance, as well as the increase in medical treatment and contrasts for tissue imaging. High affinity antibodies routinely considered for targeting, such as the brain through the blood–brain barrier (BBB), are replaced by moderate affinity binding peptides (vectors), which penetrate at high influxes not achievable by antibodies.


2012 ◽  
Vol 1820 (3) ◽  
pp. 291-317 ◽  
Author(s):  
Tracy R. Daniels ◽  
Ezequiel Bernabeu ◽  
José A. Rodríguez ◽  
Shabnum Patel ◽  
Maggie Kozman ◽  
...  

2012 ◽  
Vol 84 (11) ◽  
pp. 2479-2498 ◽  
Author(s):  
Chaofeng Dai ◽  
Arpana Sagwal ◽  
Yunfeng Cheng ◽  
Hanjing Peng ◽  
Weixuan Chen ◽  
...  

Carbohydrate biomarkers play very important roles in a wide range of biological and pathological processes. Compounds that can specifically recognize a carbohydrate biomarker are useful for targeted delivery of imaging agents and for development of new diagnostics. Furthermore, such compounds could also be candidates for the development of therapeutic agents. A tremendous amount of active work on synthetic lectin mimics has been reported in recent years. Amongst all the synthetic lectins, boronic-acid-based lectins (boronolectins) have shown great promise. Along this line, four classes of boronolectins including peptide-, nucleic-acid-, polymer-, and small-molecule-based ones are discussed with a focus on the design principles and recent advances. We hope that by presenting the potentials of this field, this review will stimulate more research in this area.


2018 ◽  
Vol 16 (1) ◽  
pp. 4-20 ◽  
Author(s):  
Marina A Dumpis ◽  
Dmitrii N Nikolayev ◽  
Elena V Litasova ◽  
Viktor V Iljin ◽  
Mariya A Brusina ◽  
...  

The review deals with the properties of fullerenes and their derivatives and the possibility of their use in biology and medicine. Fullerenes can exert an antioxidant effect in biological systems, catching active forms of oxygen, and oxidative, giving the fullerene photosensitizing properties. The lipophilic fullerene molecules possessing membrane - tropic action interact with various biological structures and can change the functions of these structures, increasing the lipophilicity of the active molecule (amino acids, nucleic acids, proteins, etc.). Data on the biological effect of fullerenes in in vitro and in vivo experiments are given. Examples of targeted delivery of known therapeutic agents. (For citation: Dumpis MA, Nikolaev DN, Litasova EV, et al. Biological activity of fullerenes - reality and prospects. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):4-20. doi: 10.17816/RCF1614-20).


2019 ◽  
Vol 45 (6) ◽  
pp. 783-792 ◽  
Author(s):  
A. A. Voitova ◽  
M. D. Dmitrieva ◽  
M. A. Dymova ◽  
N. S. Vasileva ◽  
A. A. Nushtaeva ◽  
...  

2020 ◽  
Vol 12 (567) ◽  
pp. eaay3724
Author(s):  
Suraj U. Hettiarachchi ◽  
Yen-Hsing Li ◽  
Jyoti Roy ◽  
Fenghua Zhang ◽  
Estela Puchulu-Campanella ◽  
...  

Idiopathic pulmonary fibrosis (IPF) is a lethal disease with an average life expectancy of 3 to 5 years. IPF is characterized by progressive stiffening of the lung parenchyma due to excessive deposition of collagen, leading to gradual failure of gas exchange. Although two therapeutic agents have been approved from the FDA for IPF, they only slow disease progression with little impact on outcome. To develop a more effective therapy, we have exploited the fact that collagen-producing myofibroblasts express a membrane-spanning protein, fibroblast activation protein (FAP), that exhibits limited if any expression on other cell types. Because collagen-producing myofibroblasts are only found in fibrotic tissues, solid tumors, and healing wounds, FAP constitutes an excellent marker for targeted delivery of drugs to tissues undergoing pathologic fibrosis. We demonstrate here that a low–molecular weight FAP ligand can be used to deliver imaging and therapeutic agents selectively to FAP-expressing cells. Because induction of collagen synthesis is associated with phosphatidylinositol 3-kinase (PI3K) activation, we designed a FAP-targeted PI3K inhibitor that selectively targets FAP-expressing human IPF lung fibroblasts and potently inhibited collagen synthesis. Moreover, we showed that administration of the inhibitor in a mouse model of IPF inhibited PI3K activation in fibrotic lungs, suppressed production of hydroxyproline (major building block of collagen), reduced collagen deposition, and increased mouse survival. Collectively, these studies suggest that a FAP-targeted PI3K inhibitor might be promising for treating IPF.


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