Albumin enhances PTX delivery ability of dextran NPs and therapeutic efficacy of PTX for colorectal cancer

2019 ◽  
Vol 7 (22) ◽  
pp. 3537-3545 ◽  
Author(s):  
Xinyu Zhang ◽  
Ruhe Zhang ◽  
Jun Huang ◽  
Moucheng Luo ◽  
Xuewen Chen ◽  
...  

The nanoassemblies of Dex6k–BSA–PTX and the pH-responsive drug release for anti-tumor applications in vivo.

2018 ◽  
Vol 14 (5) ◽  
pp. 432-439 ◽  
Author(s):  
Juliana M. Juarez ◽  
Jorgelina Cussa ◽  
Marcos B. Gomez Costa ◽  
Oscar A. Anunziata

Background: Controlled drug delivery systems can maintain the concentration of drugs in the exact sites of the body within the optimum range and below the toxicity threshold, improving therapeutic efficacy and reducing toxicity. Mesostructured Cellular Foam (MCF) material is a new promising host for drug delivery systems due to high biocompatibility, in vivo biodegradability and low toxicity. Methods: Ketorolac-Tromethamine/MCF composite was synthesized. The material synthesis and loading of ketorolac-tromethamine into MCF pores were successful as shown by XRD, FTIR, TGA, TEM and textural analyses. Results: We obtained promising results for controlled drug release using the novel MCF material. The application of these materials in KETO release is innovative, achieving an initial high release rate and then maintaining a constant rate at high times. This allows keeping drug concentration within the range of therapeutic efficacy, being highly applicable for the treatment of diseases that need a rapid response. The release of KETO/MCF was compared with other containers of KETO (KETO/SBA-15) and commercial tablets. Conclusion: The best model to fit experimental data was Ritger-Peppas equation. Other models used in this work could not properly explain the controlled drug release of this material. The predominant release of KETO from MCF was non-Fickian diffusion.


2020 ◽  
Vol 16 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Yuzhu Hu ◽  
Xiaoye Chen ◽  
Zongyuan Li ◽  
Songping Zheng ◽  
Yongzhong Cheng

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.


Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 462 ◽  
Author(s):  
Kevin Chih-Yang Huang ◽  
Shu-Fen Chiang ◽  
William Tzu-Liang Chen ◽  
Tsung-Wei Chen ◽  
Ching-Han Hu ◽  
...  

Programmed cell death-1 (PD-1) has demonstrated impressive clinical outcomes in several malignancies, but its therapeutic efficacy in the majority of colorectal cancers is still low. Therefore, methods to improve its therapeutic efficacy in colorectal cancer (CRC) patients need further investigation. Here, we demonstrate that immunogenic chemotherapeutic agents trigger the induction of tumor PD-L1 expression in vitro and in vivo, a fact which was validated in metastatic CRC patients who received preoperatively neoadjuvant chemotherapy (neoCT) treatment, suggesting that tumor PD-L1 upregulation by chemotherapeutic regimen is more feasible via PD-1/PD-L1 immunotherapy. However, we found that the epigenetic control of tumor PD-L1 via DNA methyltransferase 1 (DNMT1) significantly influenced the response to chemotherapy. We demonstrate that decitabine (DAC) induces DNA hypomethylation, which not only directly enhances tumor PD-L1 expression but also increases the expression of immune-related genes and intratumoral T cell infiltration in vitro and in vivo. DAC was found to profoundly enhance the therapeutic efficacy of PD-L1 immunotherapy to inhibit tumor growth and prolong survival in vivo. Therefore, it can be seen that DAC remodels the tumor microenvironment to improve the effect of PD-L1 immunotherapy by directly triggering tumor PD-L1 expression and eliciting stronger anti-cancer immune responses, providing potential clinical benefits to CRC patients in the future.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 736
Author(s):  
Sharif Md Abuzar ◽  
Eun Jung Park ◽  
Yeji Seo ◽  
Juseung Lee ◽  
Seung Hyuk Baik ◽  
...  

Colorectal cancer with peritoneal metastasis has a poor prognosis because of inadequate responses to systemic chemotherapy. Cytoreductive surgery followed by intraperitoneal (IP) chemotherapy using oxaliplatin has attracted attention; however, the short half-life of oxaliplatin and its rapid clearance from the peritoneal cavity limit its clinical application. Here, a multivesicular liposomal (MVL) depot of oxaliplatin was prepared for IP administration, with an expected prolonged effect. After optimization, a combination of phospholipids, cholesterol, and triolein was used based on its ability to produce MVL depots of monomodal size distribution (1–20 µm; span 1.99) with high entrapment efficiency (EE) (92.16% ± 2.17%). An initial burst release followed by a long lag phase of drug release was observed for the MVL depots system in vitro. An in vivo pharmacokinetic study mimicking the early postoperative IP chemotherapy regimen in rats showed significantly improved bioavailability, and the mean residence time of oxaliplatin after IP administration revealed that slow and continuous erosion of the MVL particles yielded a sustained drug release. Thus, oxaliplatin-loaded MVL depots presented in this study have potential for use in the treatment of colorectal cancer.


2021 ◽  
Vol 118 ◽  
pp. 111455
Author(s):  
Xuan Liu ◽  
Chen Wang ◽  
Xueyan Wang ◽  
Chen Tian ◽  
Yuhua Shen ◽  
...  

2015 ◽  
Vol 3 (9) ◽  
pp. 1270-1278 ◽  
Author(s):  
Ruixin Bian ◽  
Tingting Wang ◽  
Lingyu Zhang ◽  
Lu Li ◽  
Chungang Wang

A facile method was developed for the synthesis of multifunctional Fe3O4@PAA/AuNCs/ZIF-8 NPs. Furthermore, the obtained NPs with ultrahigh drug storage capacity and dual pH-responsive drug release properties were applicable in simultaneous tri-modal.


2015 ◽  
Vol 3 (46) ◽  
pp. 9033-9042 ◽  
Author(s):  
Mengni He ◽  
Jiajia Zhou ◽  
Jian Chen ◽  
Fangcai Zheng ◽  
Dongdong Wang ◽  
...  

Controlled drug release is a promising approach for cancer therapy due to its merits of reduced systemic toxicity and enhanced antitumor efficacy.


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