scholarly journals Featured Article: Chemotherapeutic delivery using pH-responsive, affinity-based release

2017 ◽  
Vol 242 (7) ◽  
pp. 692-699 ◽  
Author(s):  
Erika L Cyphert ◽  
Andrew S Fu ◽  
Horst A von Recum
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Tumor Tissue ◽  
Delivery Systems ◽  
Local Delivery ◽  
Ph Sensitive ◽  
Specific Drug ◽  
Affinity Group ◽  
Delivery Platform

Doxorubicin is a chemotherapeutic drug typically administered systemically which frequently leads to cardiac and hepatic toxicities. Local delivery to a tumor has a chance to mitigate some of these toxicities and can further be mitigated by including a means of tumor-specific drug release. Our laboratory has explored the use of molecular interactions to control the rate of drug release beyond that capable of diffusion alone. To this system, we added an additional affinity group (adamantane) to doxorubicin through a pH-sensitive hydrazone bond. The result was a modified doxorubicin which had an even higher affinity to our drug delivery polymer, and virtually no release in normal conditions, but showed accelerated release of drug in tumor-like low pH. Further, we show that adamantane-modified doxorubicin (adamantane-doxorubicin) and cleaved adamantane-doxorubicin showed equivalent capacity to kill human U-87 glioblastoma cells in vitro as unmodified doxorubicin. Taken together, these data demonstrate our ability to load high levels of modified chemotherapeutic drugs into our affinity-based delivery platform and deliver these drugs almost exclusively in the acidic microenvironments, such as those surrounding the tumor tissue via pH-cleavable bond while minimizing drug delivery in neutral pH tissue, with the ultimate goal of reducing systemic through better local delivery. Impact statement Doxorubicin (DOX) is especially cytotoxic to the heart, liver, kidneys, and healthy tissues surrounding the tumor microenvironment. This systemic toxicity can be partially addressed by local, tumor-specific drug delivery systems. While pH-sensitive DOX delivery systems have been developed by several other groups, many lack a prolonged and consistent release profile required to successfully treat heterogeneous tumors. Our system of a chemically modified form of DOX combined with an affinity-based cyclodextrin delivery system is capable of delivering DOX for 87 days while maintaining its the drug cytotoxicity. This finding is particularly relevant to improving cancer treatments because it enables regulated local delivery of DOX specifically to tumor tissue and allows the drug to be continuously delivered over a therapeutically relevant amount of time.

scholarly journals ROS-triggered self-accelerating drug release nanosystem with charge conversion for enhanced cancer therapy

2020 ◽  
Author(s):  
Xinyi Zhang ◽  
Tiantian Zhu ◽  
Yaxin Miao ◽  
Lu Zhou ◽  
Weifang Zhang
Keyword(s):  
Drug Release ◽  
Tumor Tissue ◽  
Anticancer Therapy ◽  
Cell Uptake ◽  
Oxygen Species ◽  
Anticancer Drug Delivery ◽  
Tocopheryl Succinate ◽  
Delivery Platform

Abstract Background: The enhancement tumor retention and of cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS) level inducing drug release pattern was constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle.Results: The surface charge of this system can be converted from negative to positive for enhanced tumor cell uptake in response to the weakly acidic tumor tissue. In addition, methionine-based system was dissociated in a ROS-rich intracellular environment, resulting in a phase transition and the release of DOX. Then, the exposed α-tocopheryl succinate (α-TOS) segments can be capable of producing ROS, which further induced the self-amplifiable disassembly of the micelles and drug release. Conclusions: We confirmed efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro. The system exhibited outstanding tumor inhibition capability in vivo, indicating that dual stimuli nanosytem would be great potential as an anticancer drug delivery platform.

scholarly journals Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Pooja Sharma ◽  
Anuj Chawla ◽  
Pravin Pawar
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Ph Sensitive ◽  
Time Dependent ◽  
Wet Granulation ◽  
Design Development ◽  
Caecal Content ◽  
S 100 ◽  
Eudragit S 100

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. Thein vitrodrug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highestin vitrodrug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

Schiff base-containing dextran nanogel as pH-sensitive drug delivery system of doxorubicin: Synthesis and characterization

2018 ◽  
Vol 33 (2) ◽  
pp. 170-181 ◽  
Author(s):  
Hongying Su ◽  
Wen Zhang ◽  
Yayun Wu ◽  
Xiaodong Han ◽  
Gang Liu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Schiff Base ◽  
Drug Release ◽  
Drug Delivery System ◽  
Delivery System ◽  
Ph Sensitive ◽  
Cell Uptake ◽  
Stimuli Responsive ◽  
Drug Release Profile

Stimuli-responsive hydrogels have been widely researched as carrier systems, due to their excellent biocompatibility and responsiveness to external physiologic environment factors. In this study, dextran-based nanogel with covalently conjugated doxorubicin (DOX) was developed via Schiff base formation using the inverse microemulsion technique. Since the Schiff base linkages are acid-sensitive, drug release profile of the DOX-loaded nanogel would be pH-dependent. In vitro drug release studies confirmed that DOX was released much faster under acidic condition (pH 2.0, 5.0) than that at pH 7.4. Approximately 66, 28, and 9% of drug was released in 72 h at pH 2.0, 5.0, and 7.4, respectively. Cell uptake by the human breast cancer cell (MCF-7) demonstrated that the DOX-loaded dextran nanogel could be internalized through endocytosis and distributed in endocytic compartments inside tumor cells. These results indicated that the Schiff base-containing nanogel can serve as a pH-sensitive drug delivery system. And the presence of multiple aldehyde groups on the nanogel are available for further conjugations of targeting ligands or imaging probes.

scholarly journals Nanoparticles vs. nanofibers: a comparison of two drug delivery systems on assessing drug release performance in vitro

2015 ◽  
Vol 18 (7) ◽  
pp. 678-689 ◽  
Author(s):  
Xiaoqian Shan ◽  
Changsheng Liu ◽  
Fengqian Li ◽  
Chunfa Ouyang ◽  
Qun Gao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Delivery Systems

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

2009 ◽  
Vol 68 (2) ◽  
pp. 245-249 ◽  
Author(s):  
Cui-Yun Yu ◽  
Bo-Cheng Yin ◽  
Wei Zhang ◽  
Si-Xue Cheng ◽  
Xian-Zheng Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Ph Sensitive ◽  
Release Property

NANOMEDICINES: DELIVERING DRUGS USING BOTTOM UP NANOTECHNOLOGY

2005 ◽  
Vol 04 (05n06) ◽  
pp. 855-861 ◽  
Author(s):  
MARTIN GARNETT
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Biodegradable Polymers ◽  
Drug Loading ◽  
Dna Delivery ◽  
Delivery Systems ◽  
The Body ◽  
Nanosized Materials

The use of nanosized materials changes the way in which drugs are handled by the body and offers opportunities to improve drug delivery. The physiological mechanisms controlling the distribution of nanosized materials (enhanced permeability and retention effect, cellular uptake pathways and opsonisation/elimination of nanoparticles) are described. Two different nanosized drug delivery systems are considered; drug delivery and DNA delivery. The deficiencies of currently available biodegradable polymers for preparation of drug containing nanoparticles are mainly the amount of drug that can be incorporated and the rapid rate of drug release. The development of new biodegradable polymers which can interact with the drug and so significantly increase drug loading and decrease the rate of drug release are outlined. DNA delivery necessitates overcoming a variety of biological barriers. We are developing polyelectrolyte complexes of DNA with cationic polyamidoamines (PAA) as a delivery system. Complexing PAA with DNA results in good transfection of cells in vitro. However, in vivo, a more complex arrangement of PAA, Polyethylene glycol-PAA copolymers, DNA and the use of ligands will be required. Despite these efforts, further developments will be needed in nanotechnology for both drug and DNA nanoparticle delivery systems to achieve our clinical objectives.

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