Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

2016 ◽  
Vol 5 (10) ◽  
pp. 1089-1094 ◽  
Author(s):  
Anton A. A. Smith ◽  
Kaja Zuwala ◽  
Oliver Pilgram ◽  
Karen Singers Johansen ◽  
Martin Tolstrup ◽  
...  
Author(s):  
Betül Altunay ◽  
Agnieszka Morgenroth ◽  
Mohsen Beheshti ◽  
Andreas Vogg ◽  
Nicholas C. L. Wong ◽  
...  

Abstract Purpose The aim of the present paper is to review the role of HER2 antibodies, affibodies and nanobodies as vehicles for imaging and therapy approaches in breast cancer, including a detailed look at recent clinical data from antibody drug conjugates and nanobodies as well as affibodies that are currently under development. Results Clinical and preclinical studies have shown that the use of monoclonal antibodies in molecular imaging is impaired by slow blood clearance, associated with slow and low tumor uptake and with limited tumor penetration potential. Antibody fragments, such as nanobodies, on the other hand, can be radiolabelled with short-lived radioisotopes and provide high-contrast images within a few hours after injection, allowing early diagnosis and reduced radiation exposure of patients. Even in therapy, the small radioactively labeled nanobodies prove to be superior to radioactively labeled monoclonal antibodies due to their higher specificity and their ability to penetrate the tumor. Conclusion While monoclonal antibodies are well established drug delivery vehicles, the current literature on molecular imaging supports the notion that antibody fragments, such as affibodies or nanobodies, might be superior in this approach.


2014 ◽  
Vol 50 (37) ◽  
pp. 4827-4830 ◽  
Author(s):  
Miao Yang ◽  
Dawei Xu ◽  
Linhai Jiang ◽  
Lin Zhang ◽  
Derek Dustin ◽  
...  

We report here a facile approach to prepare filamentous supramolecular peptide–drug conjugates with precise drug/carrier stoichiometry, nearly 100% loading efficiency and exceptional anti-cancer drug efficacy for chemotherapy.


2018 ◽  
Vol 6 (4) ◽  
pp. 666-674 ◽  
Author(s):  
Sanjoy Samanta ◽  
Chathuranga C. De Silva ◽  
Porakrit Leophairatana ◽  
Jeffrey T. Koberstein

Main-chain polyacetal drug conjugates are temperature responsive and pH degradable and can be designed to selectively target, retain and release drug in hyperthermic tumor tissue.


2018 ◽  
Vol 18 (5) ◽  
pp. 439-457 ◽  
Author(s):  
Merina Mariyam ◽  
Kajal Ghosal ◽  
Sabu Thomas ◽  
Nandakumar Kalarikkal ◽  
Mahima S. Latha

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.


Author(s):  
Sahil Kumar ◽  
Bandna Sharma ◽  
Tilak R. Bhardwaj ◽  
Rajesh K. Singh

Aims: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as anticancer drug specifically to the colon for the proficient treatment of colon cancer. Background: Colon cancer (CC) is the third commonly detected tumor worldwide and it make up about 10 % of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. Objective: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to polymeric backbone to give desired polymer linked prodrug. The azo reductase enzyme present in colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. Methods: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azobond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. Results: The synthesized conjugates were demonstrated to be stable in simulated upper gastro-intestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. Conclusion: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be the promising candidates for the site-specific treatment of colon cancer with least detrimental side-effects.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 427
Author(s):  
Amin Mirzaaghasi ◽  
Yunho Han ◽  
So-Hee Ahn ◽  
Chulhee Choi ◽  
Ji-Ho Park

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.


Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3589
Author(s):  
Rui Liu ◽  
Alessandro Poma

Despite the tremendous efforts made in the past decades, severe side/toxic effects and poor bioavailability still represent the main challenges that hinder the clinical translation of drug molecules. This has turned the attention of investigators towards drug delivery vehicles that provide a localized and controlled drug delivery. Molecularly imprinted polymers (MIPs) as novel and versatile drug delivery vehicles have been widely studied in recent years due to the advantages of selective recognition, enhanced drug loading, sustained release, and robustness in harsh conditions. This review highlights the design and development of strategies undertaken for MIPs used as drug delivery vehicles involving different drug delivery mechanisms, such as rate-programmed, stimuli-responsive and active targeting, published during the course of the past five years.


2021 ◽  
pp. e00663
Author(s):  
Tarun Mateti ◽  
Surabhi Aswath ◽  
Anoop Kishore Vatti ◽  
Agneya Kamath ◽  
Anindita Laha

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