Modular Synthesis of Amphiphilic Chitosan Derivatives Based on Copper-Free Click Reaction for Drug Delivery

Author(s):  
Yu Tao ◽  
Ding Qu ◽  
Chunli Tian ◽  
Yingshuang Huang ◽  
Lingjing Xue ◽  
...  
2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.


2021 ◽  
Vol 2 (4) ◽  
pp. 795-816
Author(s):  
Md Salman Shakil ◽  
Kazi Mustafa Mahmud ◽  
Mohammad Sayem ◽  
Mahruba Sultana Niloy ◽  
Sajal Kumar Halder ◽  
...  

Cancer is one of the major causes of death worldwide. Chemotherapeutic drugs have become a popular choice as anticancer agents. Despite the therapeutic benefits of chemotherapeutic drugs, patients often experience side effects and drug resistance. Biopolymers could be used to overcome some of the limitations of chemotherapeutic drugs, as well as be used either as anticancer agents or drug delivery vehicles. Chitosan is a biocompatible polymer derived from chitin. Chitosan, chitosan derivatives, or chitosan nanoparticles have shown their promise as an anticancer agent. Additionally, functionally modified chitosan can be used to deliver nucleic acids, chemotherapeutic drugs, and anticancer agents. More importantly, chitosan-based drug delivery systems improved the efficacy, potency, cytotoxicity, or biocompatibility of these anticancer agents. In this review, we will investigate the properties of chitosan and chemically tuned chitosan derivatives, and their application in cancer therapy.


2006 ◽  
Vol 58 (8) ◽  
pp. 1021-1032 ◽  
Author(s):  
Shruti Chopra ◽  
Saiqa Mahdi ◽  
Jasjeet Kaur ◽  
Zeenat Iqbal ◽  
Sushma Talegaonkar ◽  
...  

RSC Advances ◽  
2015 ◽  
Vol 5 (128) ◽  
pp. 105901-105907 ◽  
Author(s):  
Guan-Hai Wang ◽  
Hui-Kang Yang ◽  
Yi Zhao ◽  
Da-Wei Zhang ◽  
Li-Ming Zhang ◽  
...  

In this work, novel biodegradable cationic micelles were prepared based on poly-(N-ε-carbobenzyloxy-l-lysine) (PZLL) and chitosan (CS) by click reaction, and applied for co-delivery of doxorubicin (DOX) and p53 plasmid.


2021 ◽  
Author(s):  
Miao Deng ◽  
Jing-Dong Rao ◽  
Rong Guo ◽  
Man Li ◽  
Qin He

Over the past decades, nano-drug delivery systems have shown great potential in improving tumor treatment. And the controllability and design flexibility of nanoparticles endow them a broad development space. The particle size is one of the most important factors affecting the potency of nano-drug delivery systems. Large-size (100–200 nm) nanoparticles are more conducive to long circulation and tumor retention, but have poor tumor penetration; small-size (<50 nm) nanoparticles can deeply penetrate tumor but are easily cleared. Most of the current fixed-size nanoparticles are difficult to balance the retention and penetration, while the proposal of size-adjustable nano-drug delivery systems offers a solution to this paradox. Many endogenous and exogenous stimuli, such as acidic pH, upregulated enzymes, temperature, light, catalysts, redox conditions, and reactive oxygen species, can trigger the in situ transformation of nanoparticles based on protonation, hydrolysis, click reaction, phase transition, photoisomerization, redox reaction, etc. In this review, we summarize the principles and applications of stimuli-responsive size-adjustable strategies, including size-enlargement strategies and size-shrinkage strategies. We also propose the challenges faced by size-adjustable nano-drug delivery systems, hoping to promote the development of this strategy.


2016 ◽  
Vol 32 (1) ◽  
pp. 92-107 ◽  
Author(s):  
Ratjika Wongwanakul ◽  
Suree Jianmongkol ◽  
Pattarapond Gonil ◽  
Warayuth Sajomsang ◽  
Rawiwan Maniratanachote ◽  
...  

The development of different chitosan derivatives for medical applications has increased recently. Among these chitosan derivatives, quaternized chitosan was designed to improve the solubility of chitosan in biological fluids for oral drug delivery while retaining the cationic character for mucoadhesion. However, the biocompatibility of quaternized chitosan on the human intestine is unknown. In this study, we aimed to examine the potential biological effects of quaternized chitosan on the intestinal barrier, in terms of cell proliferation and cell differentiation, using the Caco-2 cell line as an in vitro model. The lower the degree of substitution of quaternized chitosan, the lower the cytotoxic and anti-proliferative effect on Caco-2 cells. In addition, the anti-proliferative effect of quaternized chitosan might induce a cell cycle disturbance and differentiation delay. Long-term continuous exposure (9 days) to quaternized chitosan caused a delay in differentiation of the Caco-2 cells even at non-cytotoxic quaternized chitosan doses (0.005% (w/v)), as shown by the low level of alkaline phosphatase in the quaternized chitosan–treated group compared to the control cells. In contrast, short-term discontinuous exposure to quaternized chitosan (0.005% (w/v) for 4 h/day over 9 days) that more realistically mimics the daily intestinal exposure did not inhibit the intestinal differentiation of Caco-2 cells. Thus, the use of a low degree of substitution and a low concentration of quaternized chitosan resulted in a good biocompatibility to the intestinal barrier supporting the potential usefulness of quaternized chitosan in the application of an oral drug delivery system.


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