Enhancing Drug Delivery with Methyl Hydroxyethyl Cellulose-based Nanoparticles

Introduction

Drug delivery systems (DDS) are crucial tools for enhancing the efficacy and safety of drug treatments. DDS are designed to ensure that therapeutic agents are delivered to the intended site of action in optimal concentrations and timing without affecting healthy tissues. However, conventional drug delivery techniques have limitations in terms of their ability to target specific cells or tissues and their drug release rate. To overcome these limitations, researchers and clinicians have developed innovative DDS based on nanotechnology.

Nanoparticles have unique properties that make them ideal for drug delivery. They possess a large surface area-to-volume ratio, allowing for increased drug-loading capacity and reduced dosages. Additionally, nanoparticles can be functionalized with various ligands, such as peptides, antibodies, and aptamers, to target specific cells or tissues. Finally, nanoparticles allow for a controlled drug release, improving efficacy and reducing side effects.

Several types of nanoparticles, including liposomes, polymersomes, dendrimers, and nanoparticles made of metals and metal oxides have been developed and used as DDS. One such DDS is methyl hydroxyethyl cellulose (MHEC) nanoparticles, which have excellent biocompatibility, biodegradability, and low toxicity. MHEC-based nanoparticles have been explored as a drug or gene delivery system for various diseases, such as cancer, diabetes, and inflammation.

In this review, we will discuss recent research on MHEC-based nanoparticles as drug delivery systems for mitigating the limitations of conventional drug delivery methods.

MHEC-based nanoparticles

MHEC is a cellulose derivative obtained by the chemical modification of cellulose. It has been utilized in various fields, including pharmaceuticals, cosmetics, and food. MHEC is amorphous, water-soluble, and biodegradable, making it an ideal material for drug delivery. The incorporation of MHEC into nanoparticles enhances their characteristics, such as stability, loading capacity, and controlled release. MHEC-based nanoparticles have been formulated through different methods, including ionic gelation, precipitation, and emulsion methods.

The ionic gelation method involves the crosslinking of two oppositely charged polymers with the help of ionic interaction. In this method, MHEC is used as the cationic polymer, while anionic polymers, such as sodium alginate, chondroitin sulfate, or hyaluronic acid, are used as the counter polymer to form nanoparticles. This method is straightforward and cost-effective. However, the particle size tends to be relatively large and broad, limiting their clinical use.

The precipitation method involves the spontaneous formation of nanoparticles by mixing the drug, MHEC, and solvent. This method is simple and does not require surfactants or organic solvents, reducing toxicity. However, the particle size and morphology depend on the solvent used, the solvent ratio, and the precipitation time.

The emulsion method involves the preparation of the oil-in-water or water-in-oil emulsion, followed by solvent evaporation or precipitation to produce nanoparticles. The presence of an emulsifying agent, such as polyvinyl alcohol or Tween 80, stabilizes the emulsion, resulting in a narrow size distribution and spherical shape of the nanoparticles. This method allows for incorporating hydrophobic drugs into the nanoparticles. However, it requires organic solvents, increasing the toxicity and complicating the purification process.

MHEC-based nanoparticle drug delivery

MHEC-based nanoparticles have been explored for delivering various therapeutic agents, including drugs and genes, to the target site of action. In this section, we will discuss some of the recent studies investigating the use of MHEC-based nanoparticles for drug delivery.

Cancer treatment

Cancer is one of the leading causes of mortality worldwide, and conventional chemotherapy has significant drawbacks, including non-specific targeting, poor pharmacokinetics, and dose-limiting toxicity. MHEC-based nanoparticles offer advantages such as targeted drug delivery, sustained release, and enhanced efficacy.

Li et al. developed MHEC nanoparticles loaded with the anticancer drug, paclitaxel, for the treatment of breast cancer (Li et al., 2019). The nanoparticles exhibited a narrow size distribution and improved drug solubility. In vitro studies showed that the drug-loaded nanoparticles had higher cytotoxicity towards breast cancer cells compared to free paclitaxel. Moreover, in vivo studies on mice showed that the nanoparticles had a prolonged circulation time and enhanced tumor growth inhibition compared to the free drug.

Another study investigated the potential of MHEC nanoparticles conjugated with an antibody against the prostate-specific membrane antigen (PSMA) for targeted drug delivery (Li et al., 2021). The authors loaded the nanoparticles with docetaxel and evaluated their efficacy against prostate cancer cells in vitro and in vivo. The results showed that the nanoparticles had high cellular uptake and cytotoxicity towards PSMA-expressing cells compared to non-expressing cells. Additionally, the nanoparticles improved the pharmacokinetics and biodistribution of the drug, resulting in enhanced tumor growth inhibition and prolonged survival time in mice.

Diabetes treatment

Diabetes is a chronic metabolic disorder characterized by high blood sugar levels and affects millions of people worldwide. The conventional treatment involves insulin injections, which have limitations such as non-specific targeting and poor patient compliance. MHEC-based nanoparticles offer an alternative treatment option with advantages such as targeted delivery, sustained release, and reduced dosages.

Wang et al. developed MHEC nanoparticles loaded with insulin for the treatment of diabetes (Wang et al., 2018). The authors investigated the influence of particle size, insulin loading, and MHEC concentration on the release profile and bioactivity of insulin. The results showed that the nanoparticles had improved insulin stability and bioactivity compared to free insulin. Additionally, the nanoparticles exhibited sustained insulin release over several days and reduced blood glucose levels in diabetic rats.

Another study explored the potential of MHEC nanoparticles loaded with curcumin, a natural antioxidant, and anti-inflammatory compound, for the treatment of diabetes-associated osteoporosis (Zhang et al., 2020). The authors investigated the effect of curcumin-loaded nanoparticles on osteoblast proliferation, differentiation, and mineralization in vitro and on bone mass and architecture in vivo. The results showed that the nanoparticles improved osteoblast differentiation and mineralization and increased bone mass and architecture in diabetic rats.

Inflammation treatment

Inflammation is a complex physiological response to various stimuli, such as infection, injury, or autoimmune disorders. Inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease, affect millions of people worldwide and have limited treatment options. MHEC-based nanoparticles offer advantages such as targeted delivery, controlled release, and enhanced efficacy for the treatment of inflammatory diseases.

Peng et al. developed MHEC nanoparticles loaded with nano-selenium for the treatment of rheumatoid arthritis (Peng et al., 2017). The authors investigated the anti-inflammatory effect of the nanoparticles on human synovial fibroblasts in vitro, and on joint inflammation and destruction in vivo. The results showed that the nanoparticles had potent anti-inflammatory and anti-oxidative properties, reducing the production of various pro-inflammatory cytokines. Additionally, the nanoparticles reduced the severity of joint inflammation and destruction in rats with collagen-induced arthritis.

Another study evaluated the potential of MHEC nanoparticles loaded with the anti-inflammatory drug, dexamethasone, for the treatment of inflammatory bowel disease (Abdel-Hafez et al., 2020). The authors investigated the influence of nanoparticle size, drug loading, and MHEC concentration on the release profile and bioactivity of dexamethasone. The results showed that the nanoparticles had prolonged drug release and potent anti-inflammatory effects on human colon cancer cells in vitro and rats with colitis in vivo.

Conclusion

MHEC-based nanoparticles offer significant advantages as drug delivery systems for overcoming the limitations of conventional drug delivery techniques. MHEC-based nanoparticles have been explored for delivering various therapeutic agents, such as anticancer drugs, insulin, curcumin, and dexamethasone, for the treatment of cancer, diabetes, and inflammation. The incorporation of MHEC into nanoparticles enhances their properties, such as stability, loading capacity, and controlled release. Additionally, MHEC-based nanoparticles have excellent biocompatibility, biodegradability, and low toxicity, making them ideal for clinical translation. Overall, MHEC-based nanoparticles hold promise as an innovative and effective DDS for improving patient outcomes.