Stimuli-sensitive polymeric micelles show promise for drug delivery and chemotherapy in the future

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In a recent review published in pharmaceuticalthe researchers documented various polymeric materials that can be used to synthesize micelles, which can then be used for targeted cancer therapy by conditioning micelles to respond to stimuli.

Study: Exploring applications of micellar drug delivery systems in cancer nanomedicine.  Image credit: Sanjaya Viraj Bandara/Shutterstock
Stady: Exploring the application of micellar drug delivery systems in cancer nanomedicine. Image credit: Sanjaya Viraj Bandara/Shutterstock

background

Targeted cancer therapy is one area that has received a lot of attention over the past year, as nanotechnology is now being used to deliver chemotherapy drugs directly to a tumor or cancer cells. Besides targeted drug delivery, other areas of health and medicine, such as immune system development, imaging, and diagnostics, have also advanced with the advent of nanotechnology. Medical regulatory authorities in the United States and various European countries have approved the use of polymeric micelles and liposomes for chemotherapy.

Polymeric micelles can be designed to release drugs only in response to a specific stimulus. Tumor microenvironments differ from those in healthy tissue. Microenvironmental differences include pH, concentration of reactive oxidant species, hypoxia, glutathione concentration, and overexpressed enzymes such as hyaluronidase and metalloproteinases. These differences in the microenvironment can be used to ensure selective drug release, thereby reducing systemic exposure to chemotherapy drugs.

Polymeric micelles have a hydrophilic polymeric outer layer that reduces nonspecific absorption and increases body circulation time. Also, the nanosize of the polymeric micelles facilitates these nanoparticles to infiltrate the tumor site in response to a specific stimulus.

However, while there has been extensive research on the catalytic response of polymeric micelles in cancer treatment, available polymeric materials for the synthesis of such designed micelles have not been documented in detail.

polymeric micelles

The critical micelle concentration (CMC) is the concentration at which amphiphilic polymers form ordered micelle structures in an aqueous environment. Various methods based on surface tension, fluorometry, light scattering, osmotic pressure, electrical conductivity, and surface flour resonance are used to determine the CMCs of different polymers.

Moreover, different types of microscopes, magnetic resonance spectroscopy, neutron, X-ray, and light scattering methods can be used to characterize the micelle structures composed of different polymers.

Several hydrophilic and hydrophobic polymers have been screened for the synthesis of polymer micelles. Hydrophilic polymers such as polyethylene glycol, polysaccharides and polysaccharides[N-(2-hydroxypropyl) methacrylamide]pHPMA has the advantage of being non-toxic and biocompatible. This, therefore, allows them to circulate in the blood, target specific tissues, and reduce inflammatory responses. However, polyethylene glycol is not biodegradable, while polysaccharides decompose at higher temperatures, and pHPMA has a complex synthesis process.

Polyacrylic acid and polyglutamic acids are pH sensitive, as well as biodegradable and biocompatible, but also have disadvantages such as poor mechanical stability and high production costs, respectively. The review discusses the advantages and disadvantages of various hydrophilic and hydrophobic polymers such as polyhistidine, polyethers and polyesters.

micelles for targeted drug delivery

The review provided detailed documentation of the different types of micelles used for targeted drug delivery based on the type of stimulation. These stimuli can either be present in the tumor microenvironment, such as conditions of hypoxia, low pH, or enzyme overexpression, or be external such as temperature, light, or localized magnetic fields.

Micelles synthesized with D-α-tocopherol acid polyethylene glycoloxinate, conjugated curcumin (HC), polyethylene glycol, and poly(ε-caprolactone) were used to design pH-sensitive micelles for targeted chemotherapy. Furthermore, polyethylene glycol and beta-cyclodextrin conjugates were used to design polymeric micelles targeting tissues with a high concentration of reactive oxidative species.

Other types of micelles discussed in the review included hypoxia-sensitive micelles that were made from various polymers, such as hydrophilic polysaccharides combined with curcumin and methoxyl-poly(ethylene glycol)-co-poly(nitroimidazole-aspartate). Another example includes enzyme-sensitive micelles composed of polyethylene glycol, glucose conjugates, and polyamidamine manifolds that respond to overexpression of metalloproteins.

Thermosensitive micelles made from various polymers, including poly(N-isopropyl acrylamide), which release drugs at the tumor site based on temperature changes in the tumor environment were included in the review. In addition, the use of magnetite, magnesium oxide, and maghemite to create micelles sensitive to magnetic forces has also been included.

In addition, the authors discuss several clinical trials that evaluated the use of polymeric micelles sensitive to different stimuli in the treatment of cancer. Thus, the researchers provided a detailed explanation of the regulatory processes examining the efficacy and safety of drug delivery systems based on micro-nanoparticles.

conclusions

Overall, this comprehensive review discussed the different types of polymeric materials available for the synthesis of stimuli-sensitive micelles for targeted drug delivery and the beneficial and disadvantageous properties of these materials.

Moreover, several clinical trials have been studied effectiveness Micellar-based drug delivery systems and regulatory considerations for testing the safety and efficacy of micellar polymeric drug delivery methods were also covered in the review.

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