Thermo-Responsive Controlled-Release Nanocarriers


CD Bioparticles offers custom services to stimuli-responsive controlled-release nanocarriers using advanced techniques. Our experienced scientists have created a comprehensive platform to design the thermo-responsive controlled-release nanocarriers in order to improve the capability of controlled-release drug delivery system.

Introduction to Thermo-responsive Controlled-release Nanocarriers

Nanoparticles has been used widely for drug delivery because they preferentially accumulate in the tumor microenvironment because of the porosity of the surrounding endothelial cells. To increase the specific tissue targeting, stimulus- sensitive nanoscale systems and the stimulus at the desired area and time has been used. Temperature is a stimulus of choice among the different stimuli to optimize the overall efficiency of thermotherapy and chemotherapy for cancer treatment. In addition to the fact that localized hyperthermia helps kill cancer cells by putting the tumor tissues under a high temperature environment (42.5°C–43.5°C), the thermal stimulus could dilate vessels and change the penetrability of tumor cell membranes, promoting delivery of anti-tumor drugs. This mild hyperthermia can be obtained by using microwaves, ultrasound, radiofrequency, infrared illumination or magnetic fluid hyperthermia.

Thermo-responsive polymers exhibiting either a lower critical solution temperature (LCST) or an upper critical solution temperature (UCST) in aqueous medium could be used in controlled drug delivery systems. Temperature-sensitive polymers have LCST or UCST parameter: when the ambient temperature is lower than the LCST or higher than UCST, the polymer material manifests a water soluble property swelling state due to the hydrogen bonds between polymer chains and water molecules. The disruption of hydrogen bonds happens as the temperature increases, resulting in insolubility and collapse of the temperature-sensitive polymer. Many thermo-responsive nanocarriers have been investigated for the past 20 years with only one of them is currently under Phase III clinical trial: ThermoDox® (Celsion) which is a thermo-responsive liposomal formulation loaded by doxorubicin to treat primary liver cancer. The thermo-responsive temperature of liposomes could be modified by lipid compositions. Other temperature-sensitive properties could be found in LCST polymers(poly(N-isopropylacrylamide), Elastin-like polypeptides, etc.) and UCST polymers (Poly(N-acryloylglycinamide and copolymers, P(AAm-co-AN) and other acrylamide copolymers, Polymers bearing ureido pendant groups, etc.)

Key Features of Thermo-responsive Controlled-release Nanocarriers

  • Controlled-release nanocarriers can protect healthy tissues from toxic drugs and decrease the side-effects by releasing in target tissues.
  • Localized hyperthermia has been widely used in the clinical treatment of tumors.
  • Tumor tissue can be killed in high temperature environment.
  • Thermal stimulation can dilate blood vessels, change the permeability of tumor cell membrane, and promote anti-tumor drugs delivery.
  • The time and place of drug release in the body can be artificially controlled by the regulation of heat sources.
  • Controlled-release can prevent drug decomposition.

Figure 1. Top: Schematic representation of PNIPAAm chains (black) surrounded by watermolecules (blue) as a function of temperature. Bottom-right: chemical structure of PNIPAAm. The red inset shows the possible hydrogen bonds between water molecules and polymer chains. Below the LCST, polymer chains are fully hydrated and solubilized, whereas above the LCST, they interact strongly with one another, the intrachain hydrophobic effect changes the conformation of the polymer chains to a coil state, they aggregate, and phase separate from the water phase to yield a turbid suspension. (Bordat, A., et al. Adv Drug Deliv Rev. 2019, 138:167-192.)

Thermo-responsive Controlled-release Nanocarriers Applications

Both LCST nanocarriers and UCST nanocarriers have already show great potential for effective thermo-responsive drug release, which could bring a therapeutic improvement for cancer treatment. New technology has been developed to improve thermo-responsive drug release. For example, Mn and Zn-doped ferrite magnetic nanoparticles (MZF-MNPs) were introduced into the polymeric micelles to function as heaters under an alternating magnetic field (AMF). Thermo-responsive can cooperate with Ca2+ and pH to develop triple-responsive drug delivery systems. It helps to regulate the controlled-release of drug.

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Quotations and Ordering

References:
1. Chendi Ding, et al. Recent advances in stimuli-responsive release function drug delivery systems for tumor treatment. Molecules. 2016, 21, 1715.
2. Yang Zheng, et al. pH and thermal dual-responsive nanoparticles for controlled drug delivery with high loading content. ACS Omega. 2017, 2: 3399−3405.
3. Alexandre Bordat, et al. Thermo-responsive polymer nanocarriers for biomedical applications. Advance Drug Delivery Review. 2019, 138:167-192.

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